The Pain Practitioner - August/September 2016 by Academy of Integrative Pain Management

27th annual MEETING ISSUE

The Pain Practitioner August / September 2016

l e a d e r s i n m u lti d is c i p l i n a r y c a r e si n c e 19 8 8

TW O SOURCES

OF PAIN

O NE SOURCE OF RELIEF

NUCYNTA® ER is the first and only FDA-approved long-acting opioid designed to control both nociceptive pain and the neuropathic pain associated with diabetic peripheral neuropathy (DPN). NUCYNTA® ER is an opioid agonist indicated for the management of: •p ain severe enough to require daily, around-theclock, long-term opioid treatment and for which alternative treatment options are inadequate • neuropathic pain associated with DPN in adults severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

Not an actual patient.

Limitations of Use • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve NUCYNTA® ER for use in patients for whom alternative treatment options (e.g., nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain •N UCYNTA® ER is not indicated as an as-needed (prn) analgesic

Please see additional Important Safety Information, including BOXED WARNING, and Brief Summary on the following pages.

TIME TO DUAL

PRESCRIBE NUCYNTA® ER FOR ONE SOURCE OF RELIEF •P roven efficacy in chronic low back pain and DPN1,2 - Based on efficacy demonstrated in a prospective, randomized, double-blind, active- and placebo-controlled, multicenter phase 3 chronic low back pain study (N=981) showing significant change in mean pain intensity from baseline in Week 15 (Week 12 of the maintenance phase) vs placebo1 - Based on efficacy demonstrated in a double-blind, parallel-group, enriched-enrollment randomized withdrawal phase 3 DPN study (N=977) showing significant change in mean pain intensity over the last week of the 12-week, double-blind, maintenance phase vs placebo2 • 5 dosage strengths: 50 mg, 100 mg, 150 mg, 200 mg, and 250 mg3* Individualize dosing based on patient’s prior analgesic treatment experience and risk factors for addiction, abuse, and misuse; titrate as needed to provide adequate analgesia and minimize adverse reactions

COVERED FOR

94%

OF COMMERCIALLY INSURED PATIENTS.‡ PREFERRED FOR UNITEDHEALTH GROUP AND SILVERSCRIPT/ CVS CAREMARK PART D PLANS‡

• Administer NUCYNTA® ER ~q12h3

VISIT NUCYNTA.COM FOR MORE INFORMATION AND TO DOWNLOAD A NUCYNTA® ER SAVINGS CARD† •$ 0 co-pay for first prescription of NUCYNTA® ER with a $25 co-pay on each additional prescription if eligible†

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and INTERACTION WITH ALCOHOL See full prescribing information for complete boxed warning. •N UCYNTA® ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow NUCYNTA® ER tablets whole to avoid exposure to a potentially fatal dose of tapentadol. (5.2) • Accidental ingestion of NUCYNTA® ER, especially in children, can result in fatal overdose of tapentadol. (5.2) •P rolonged use of NUCYNTA® ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. (5.3) • I nstruct patients not to consume alcohol or any products containing alcohol while taking NUCYNTA® ER because co-ingestion can result in fatal plasma tapentadol levels. (5.4) CONTRAINDICATIONS: Significant respiratory depression; acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment; known or suspected paralytic ileus; hypersensitivity (e.g., anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product; concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days. *Please see full Prescribing Information for DOSAGE AND ADMINISTRATION. † Some restrictions and limitations apply. See full terms and conditions available at NUCYNTA.com. Available to commercially insured and cash-paying patients only. Patients covered by Medicare, Medicaid, or any other federally funded benefit program are excluded. Patients must be 18 years of age or older. This promotion cannot be combined with any other programs, offers, or discounts. Depomed reserves the right to rescind, revoke, or amend this offer without further notice. ‡ Data on file. Depomed, Inc. formulary data are sourced from MMIT. Transaction data are sourced from SHA Health. Data are current as of July, 2015. References: 1. Buynak R, Shapiro DY, Okamoto A, et al. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase Ill study. Expert Opin Pharmocother. 2010;11(11):17871804. 2. Schwartz S, Etropolski M, Shapiro DY, et al. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011;27(1):151-162. 3. NUCYNTA® ER [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2014.

NUCYNTA® ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) WARNINGS AND PRECAUTIONS: Addiction, Abuse, and Misuse: NUCYNTA® ER contains tapentadol, an opioid agonist and a Schedule II controlled substance that can be abused in a manner similar to other opioid agonists, legal or illicit. There is a greater risk for overdose and death due to the larger amount of tapentadol present in NUCYNTA® ER. Assess risk for opioid abuse or addiction prior to prescribing NUCYNTA® ER. Addiction can occur in patients appropriately prescribed NUCYNTA® ER at recommended doses; in those who obtain the drug illicitly; and if the drug is misused or abused. Therefore, routinely monitor for signs of misuse, abuse, and addiction. Patients at increased risk (e.g., patients with a personal or family history of substance abuse or mental illness) may be prescribed NUCYNTA® ER, but use in such patients necessitates intensive counseling about the risks and proper use along with intensive monitoring for signs of addiction, abuse, and misuse. Life-threatening Respiratory Depression: Can occur at any time during the use of NUCYNTA® ER even when used as recommended. Respiratory depression from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. To reduce the risk of respiratory depression, proper dosing and titration are essential. Overestimating the dose when converting patients from another opioid product can result in fatal overdose with the first dose. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status. Neonatal Opioid Withdrawal Syndrome: Prolonged use of NUCYNTA® ER during pregnancy can result in withdrawal signs in the neonate, which may be life-threatening and require management according to protocols developed by neonatology experts. Neonatal opioid withdrawal syndrome presents as poor feeding, irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, rigidity, seizures, vomiting, diarrhea, and failure to gain weight. Interactions With Central Nervous System Depressants: Hypotension, profound sedation, coma, respiratory depression, and death may result if NUCYNTA® ER is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, tranquilizers, general anesthetics, neuroleptics, other opioids). When considering the use of NUCYNTA® ER in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. If the decision to begin NUCYNTA® ER is made, start with NUCYNTA® ER 50 mg every 12 hours, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant.

Use in Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance. Because elderly patients are more likely to have decreased renal and hepatic function, consideration should be given to starting elderly patients in the lower range of recommended doses. Closely monitor these patients, particularly when initiating and titrating NUCYNTA® ER and when given concomitantly with other drugs that depress respiration. Use in Patients With Chronic Pulmonary Disease: Patients with significant chronic obstructive pulmonary disease or cor pulmonale and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or pre-existing respiratory depression, should be monitored for respiratory depression particularly when initiating therapy and titrating with NUCYNTA® ER. Consider the use of alternative nonopioid analgesics in these patients. Hypotensive Effect: May cause severe hypotension. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor for signs of hypotension during dose initiation or titration. Avoid use in patients with circulatory shock; may cause vasodilation that can further reduce cardiac output and blood pressure. Use in Patients With Head Injury or Increased Intracranial Pressure: Monitor patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy. NUCYNTA® ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury. Seizures: May aggravate convulsions in patients with convulsive disorders and may induce or aggravate seizures. Monitor patients with a history of seizure disorders for worsened seizure control during therapy. Serotonin Syndrome: Cases of life-threatening serotonin syndrome have been reported with the concurrent use of NUCYNTA® ER and serotonergic drugs. Serotonergic drugs comprise selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, drugs that affect the serotonergic neurotransmitter system, and drugs that impair metabolism of serotonin (including MAOIs). This may occur within the recommended dose. Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g.,

tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) and can be fatal. If concomitant treatment with SSRIs, SNRIs, TCAs, or triptans is clinically warranted, careful observation of the patient is advised, particularly when initiating or titrating the dose. Use in Patients With Gastrointestinal (GI) Conditions: Contraindicated in patients with Gl obstruction including paralytic ileus; may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Avoidance of Withdrawal: Withdrawal symptoms (e.g., anxiety, sweating, insomnia, restlessness, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection) may occur: • After abrupt discontinuation or a significant dose reduction of NUCYNTA® ER in physically dependent patients. When discontinuing NUCYNTA® ER, gradually taper the dose. • If mixed agonist/antagonist (e.g., butorphanol, nalbuphine, pentazocine) and partial agonist (e.g., buprenorphine) analgesics are used in patients who have received or are receiving NUCYNTA® ER. Avoid use with mixed agonists/ antagonists and partial agonists. • If opioid antagonists (e.g., naloxone, nalmefene) are administered in physically dependent patients. Administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist. Driving and Operating Heavy Machinery: May impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA® ER and know how they will react to the medication. Hepatic Impairment: Avoid use in patients with severe hepatic impairment (Child-Pugh Score 10 to 15). In patients with moderate hepatic impairment (Child-Pugh Score 7-9), initiate treatment with NUCYNTA® ER 50 mg no more than once every 24 hours, with a maximum dose of 100 mg per day. Monitor for respiratory and CNS depression when initiating and titrating NUCYNTA® ER. Renal Impairment: Use in patients with severe renal impairment (CLCR <30 mL/min) is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

DRUG INTERACTIONS Alcohol: See BOXED WARNING. Muscle Relaxants: Monitor patients receiving muscle relaxants and NUCYNTA® ER for signs of respiratory depression that may be greater than otherwise expected. Tapentadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Anticholinergics: Use with anticholinergic products may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. USE IN SPECIFIC POPULATIONS Pregnancy/Nursing Mothers: Pregnancy Category C. NUCYNTA® ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms. Observe newborns for symptoms of neonatal opioid withdrawal syndrome. Withdrawal symptoms can occur in breast-feeding infants when maternal administration of NUCYNTA® ER is stopped. Labor and Delivery: Opioids cross the placenta and may produce respiratory depression in neonates. NUCYNTA® ER is not for use in women during and immediately prior to labor, when shorter-acting analgesics or other analgesic techniques are more appropriate. Use in Elderly, Renal Impairment, and Hepatic Impairment: See WARNINGS AND PRECAUTIONS. DRUG ABUSE AND DEPENDENCE: See BOXED WARNING OVERDOSAGE: Institute supportive measures to manage respiratory depression, circulatory shock, and pulmonary edema as required. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression. ADVERSE REACTIONS: In clinical studies, the most common (≥10%) adverse reactions were nausea, constipation, vomiting, dizziness, somnolence, and headache. Select Postmarketing Adverse Reactions: Anaphylaxis, angioedema, and anaphylactic shock have been reported very rarely with ingredients contained in NUCYNTA® ER. Advise patients how to recognize such reactions and when to seek medical attention. Panic attack has also been reported.

BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION This does not include all the information needed to use NUCYNTA® ER safely and effectively. See full Prescribing Information for NUCYNTA® ER. INDICATIONS AND USAGE NUCYNTA® ER is indicated for the management of: • p ain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate • neuropathic pain associated with diabetic peripheral neuropathy (DPN) in adults severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Limitations of Usage • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve NUCYNTA® ER for use in patients for whom alternative treatment options (e.g., nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. • NUCYNTA® ER is not indicated as an as-needed (prn) analgesic. WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; AND INTERACTION WITH ALCOHOL See full prescribing information for complete boxed warning. • NUCYNTA® ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow NUCYNTA® ER tablets whole to avoid exposure to a potentially fatal dose of tapentadol. (5.2) • Accidental ingestion of NUCYNTA® ER, especially in children, can result in fatal overdose of tapentadol. (5.2) • Prolonged use of NUCYNTA® ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. (5.3) • Instruct patients not to consume alcohol or any products containing alcohol while taking NUCYNTA® ER because co-ingestion can result in fatal plasma tapentadol levels. (5.4) CONTRAINDICATIONS Significant respiratory depression; acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment; known or suspected paralytic ileus; hypersensitivity (e.g., anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product; concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days. WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse: NUCYNTA® ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA® ER exposes users to the risks of addiction, abuse, and misuse. As modified-release products such as NUCYNTA® ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA® ER and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA® ER, and monitor all patients receiving NUCYNTA® ER for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol addiction or abuse) or mental illness (e.g., major depression).The potential for these risks should not, however, prevent the prescribing of NUCYNTA® ER for the proper management of pain in any given patient. Patients at increased risk may be prescribed modified-release opioid formulations such as NUCYNTA® ER, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA® ER along with intensive monitoring for signs of addiction, abuse, and misuse. Abuse or misuse of NUCYNTA® ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tapentadol and can result in overdose and death. Opioid agonists such as NUCYNTA® ER are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA® ER. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression has been reported with the use of modified release opioids, even when used as recommended. Respiratory depression from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA® ER, the risk is greatest during the initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with NUCYNTA® ER and following dose increases. To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA® ER are essential. Overestimating the NUCYNTA® ER dose when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental ingestion of even one dose of NUCYNTA® ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

Neonatal Opioid Withdrawal Syndrome: Prolonged use of NUCYNTA® ER during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Interactions with Central Nervous System Depressants: Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA® ER therapy. The co-ingestion of alcohol with NUCYNTA® ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol. Hypotension, profound sedation, coma, respiratory depression, and death may result if NUCYNTA® ER is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of NUCYNTA® ER in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of alcohol or illicit drugs that cause CNS depression. If the decision to begin NUCYNTA® ER is made, start with NUCYNTA® ER 50 mg every 12 hours, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant. Use in Elderly, Cachectic, and Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Therefore, closely monitor such patients, particularly when initiating and titrating NUCYNTA® ER and when NUCYNTA® ER is given concomitantly with other drugs that depress respiration. Use in Patients with Chronic Pulmonary Disease: Monitor for respiratory depression those patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or pre-existing respiratory depression, particularly when initiating therapy and titrating with NUCYNTA® ER, as in these patients, even usual therapeutic doses of NUCYNTA® ER may decrease respiratory drive to the point of apnea. Consider the use of alternative non-opioid analgesics in these patients if possible. Hypotensive Effect: NUCYNTA® ER may cause severe hypotension. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dose of NUCYNTA® ER. In patients with circulatory shock, NUCYNTA® ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA® ER in patients with circulatory shock. Use in Patients with Head Injury or Increased Intracranial Pressure: Monitor patients taking NUCYNTA® ER who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA® ER. NUCYNTA® ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with ahead injury. Avoid the use of NUCYNTA® ER in patients with impaired consciousness or coma. Seizures: NUCYNTA® ER has not been evaluated in patients with a predisposition to a seizure disorder, and such patients were excluded from clinical studies. The active ingredient tapentadol in NUCYNTA® ER may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA® ER therapy. Serotonin Syndrome: Cases of life-threatening serotonin syndrome have been reported with the concurrent use of tapentadol and serotonergic drugs. Serotonergic drugs comprise Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, drugs that affect the serotonergic neurotransmitter system (e.g. mirtazapine, trazodone, and tramadol), and drugs that impair metabolism of serotonin (including MAOIs). This may occur within the recommended dose. Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) and can be fatal. Use in Patients with Gastrointestinal Conditions: NUCYNTA® ER is contraindicated in patients with GI obstruction, including paralytic ileus. The tapentadol in NUCYNTA® ER may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Avoidance of Withdrawal: Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including NUCYNTA® ER. In these patients, mixed agonists/antagonists and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms. When discontinuing NUCYNTA® ER, gradually taper the dose. Driving and Operating Heavy Machinery: NUCYNTA® ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA® ER and know how they will react to the medication. Hepatic Impairment: A study with an immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA® ER in patients with severe hepatic impairment. Reduce the dose of NUCYNTA® ER in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when initiating and titrating NUCYNTA® ER. Renal Impairment: Use of NUCYNTA® ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: • Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] • Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3)] • Interaction with Other CNS Depressants [see Warnings and Precautions (5.4)] • Hypotensive Effects [see Warnings and Precautions (5.7)] • Gastrointestinal Effects [see Warnings and Precautions (5.11)] • Seizures [see Warnings and Precautions (5.9)] • Serotonin Syndrome [see Warnings and Precautions (5.10)] Clinical Trial Experience Commonly-Observed Adverse Reactions in Clinical Studies with NUCYNTA® ER in Patients with Chronic Pain due to Low Back Pain or Osteoarthritis The most common adverse reactions (reported by ≥10% in any NUCYNTA® ER dose group) were: nausea, constipation, dizziness, headache, and somnolence. The most common reasons for discontinuation due to adverse reactions in eight Phase 2/3 pooled studies reported by ≥1% in any NUCYNTA® ER dose group for NUCYNTA® ER- and placebo-treated patients were nausea (4% vs. 1%), dizziness (3% vs. <1%), vomiting (3% vs. <1%), somnolence (2% vs. <1%), constipation (1% vs. <1%), headache (1% vs. <1%), and fatigue (1% vs. <1%), respectively. Commonly-Observed Adverse Reactions in Clinical Studies with NUCYNTA® ER in Patients with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy The most commonly reported ADRs (incidence ≥ 10% in NUCYNTA® ER-treated subjects) were: nausea, constipation, vomiting, dizziness, somnolence, and headache. Postmarketing Experience: The following adverse reactions, not above, have been identified during post approval use of tapentadol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Psychiatric disorders: hallucination, suicidal ideation, panic attack. Anaphylaxis, angioedema, and anaphylactic shock have been reported very rarely with ingredients contained in NUCYNTA® ER. Advise patients how to recognize such reactions and when to seek medical attention. DRUG INTERACTIONS Alcohol: Concomitant use of alcohol with NUCYNTA® ER can result in an increase of tapentadol plasma levels and potentially fatal overdose of tapentadol. Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while on NUCYNTA® ER therapy. Monoamine Oxidase Inhibitors: NUCYNTA® ER is contraindicated in patients who are receiving monoamine oxidase inhibitors (MAOIs) or who have taken them within the last 14 days due to potential additive effects on norepinephrine levels, which may result in adverse cardiovascular events. CNS Depressants: The concomitant use of NUCYNTA® ER with other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol can increase the risk of respiratory depression, profound sedation, coma and death. Monitor patients receiving CNS depressants and NUCYNTA® ER for signs of respiratory depression, sedation and hypotension. When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced. Serotonergic Drugs: There have been post-marketing reports of serotonin syndrome with the concomitant use of tapentadol and serotonergic drugs (e.g., SSRIs and SNRIs). Caution is advised when NUCYNTA® ER is coadministered with other drugs that may affect serotonergic neurotransmitter systems such as SSRIs, SNRIs, MAOIs, and triptans. If concomitant treatment of NUCYNTA® ER with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Muscle Relaxants: Tapentadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Monitor patients receiving muscle relaxants and NUCYNTA® ER for signs of respiratory depression that may be greater than otherwise expected. Mixed Agonist/Antagonist Opioid Analgesics: Mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) and partial agonists (e.g., buprenorphine) may reduce the analgesic effect of NUCYNTA® ER or precipitate withdrawal symptoms. Avoid the use of mixed agonist/ antagonist analgesics in patients receiving NUCYNTA® ER. Anticholinergics: The use of NUCYNTA® ER with anticholinergic products may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. USE IN SPECIFIC POPULATIONS Pregnancy Clinical Considerations Fetal/neonatal adverse reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Observe newborns for symptoms of neonatal opioid withdrawal syndrome, such as poor feeding, diarrhea, irritability, tremor, rigidity, and seizures, and manage accordingly. Teratogenic Effects - Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. NUCYNTA® ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Labor and Delivery: Opioids cross the placenta and may produce respiratory depression in neonates. NUCYNTA® ER is not for use in women during and immediately prior to labor, when shorter acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Nursing Mothers: There is insufficient/limited information on the excretion of tapentadol in human or animal breast milk. Physicochemical and available pharmacodynamic/toxicological data on tapentadol point to excretion in breast milk and risk to the breastfeeding child cannot be excluded. Because of the potential for adverse reactions in nursing infants from NUCYNTA® ER, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Withdrawal symptoms can occur in breast-feeding infants when maternal administration of

NUCYNTA® ER is stopped. Pediatric Use: The safety and efficacy of NUCYNTA® ER in pediatric patients less than 18 years of age have not been established. Geriatric Use: Of the total number of patients in Phase 2/3 double-blind, multiple-dose clinical studies of NUCYNTA® ER, 28% (1023/3613) were 65 years and over, while 7% (245/3613) were 75 years and over. No overall differences in effectiveness or tolerability were observed between these patients and younger patients. In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. Because elderly patients are more likely to have decreased renal and hepatic function, consideration should be given to starting elderly patients with the lower range of recommended doses. Renal Impairment: The safety and effectiveness of NUCYNTA® ER have not been established in patients with severe renal impairment (CLCR <30 mL/min). Use of NUCYNTA® ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known. Hepatic Impairment: Administration of tapentadol resulted in higher exposures and serum levels of tapentadol in subjects with impaired hepatic function compared to subjects with normal hepatic function. The dose of NUCYNTA® ER should be reduced in patients with moderate hepatic impairment (Child-Pugh Score 7 to 9). Use of NUCYNTA® ER is not recommended in severe hepatic impairment (Child-Pugh Score 10 to 15). DRUG ABUSE AND DEPENDENCE Controlled Substance: NUCYNTA® ER contains tapentadol, a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone. NUCYNTA® ER can be abused and is subject to misuse, addiction, and criminal diversion. The high drug content in the extended release formulation adds to the risk of adverse outcomes from abuse and misuse. Abuse: All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited to the following examples: the use of a prescription or over-the-counter drug to get “high,” or the use of steroids for performance enhancement and muscle build up. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and include: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “Drug-seeking” behavior is very common to addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated claims of loss of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers, and people suffering from untreated addiction. Preoccupation with achieving pain relief can be appropriate behavior in a patient with poor pain control. Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction. NUCYNTA® ER, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. Dependence: Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. NUCYNTA® ER should not be abruptly discontinued. If NUCYNTA® ER is abruptly discontinued in a physically-dependent patient, an abstinence syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms. OVERDOSAGE Clinical Presentation: Acute overdosage with opioids can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and sometimes pulmonary edema, bradycardia, hypotension and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations. Treatment of Overdose: In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques. Rx Only

Academy of Integrative Pain Management

The Pain Practitioner

www.aapainmanage.org August/September 2016

To access the virtual magazine, go to newsstand.aapainmanage.org

7 NOTES FROM THE FIELD What’s in Our Toolbox? By Bob Twillman, PhD, FAPM, Executive Director PAGE 17

8 MEMBERSHIP The Academy of Integrative Pain Management & the National Pain Strategy: Yesterday, Today, and Tomorrow 10 MEMBERSHIP Academy Forms and Staffs New Business Development and Brand Marketing Department By Bob Twillman, PhD, FAPM, Executive Director 12 education Chronic Pain a Key Focus of the NCCIH Research Strategy: Interview with Josephine P. Briggs, MD By Debra Nelson-Hogan, Director of Professional Development 14 PROFESSIONAL DEVELOPMENT New Name, Same Game: After 27 years, John Garzione, DPT, is Still Fired Up About the Academy By Debra Nelson-Hogan, Director of Professional Development 16 ADVOCACY SPPAN: Working for (and with!) You to Make Integrative Pain Care Attainable for All By Katie Duensing, JD, SPPAN Assistant Director for Legislative and Regulatory Affairs

PAGE 22

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17 MEMBER profile Better Education and Mentorship to Advance Pain Management in Primary Care: Interview with Robert L. Rich, Jr., MD By Debra Nelson-Hogan, Director of Professional Development 22 Trust, But Verify: Essentials of Urine Drug Testing in Pain Medicine By Gary M. Reisfield, MD, and Roger L. Bertholf, PhD

27th annual MEETING special section 31 Welcome 32 Agenda 34 Course Summaries 46 Exhibitor Listings

And More, on the Web... WATCH An Integrative Approach for Treating Chronic Pain,

JOIN US LIVE

From the our 27th Annual Meeting! We’ll be live tweeting from San Antonio during our Annual Meeting, September 21-25. Go to #TeamPainCare to see minute-by-minute updates. http://www.twittercom/aapainmanage

Poor Sleep, and Depression Ashwin Mehta, MD, talks about this cluster of symptoms and how clinicians can avoid reaching for the prescription pad when a patient is depressed. https://goo.gl/kbvOkS COMMUNITY Integrative Pain Management

Want the latest on integrative pain management news and techniques? Join our Google+ Community and meet other like-minded pain professionals. https://goo.gl/aooPCj LEARN ONLINE Advanced Credentialed Pain Practitioner Curriculum Review Course Can’t make to our annual review course in person? Take it online at your leisure!

https://goo.gl/dC9Rgj

GO DIGITAL! Get the Interactive Edition of The Pain Practitioner

Want more from us? Check out the digital edition of our magazine, featuring the same outstanding editorial and digital-only content like videos, slideshows, and useful links. http://goo.gl/lLcrV0

Subscribe to The Pain Practitioner even if you are not a member... you can still get this bi-monthly publication for just $50 annually! Send your check to the Academy of Integrative Pain Management, 975 Morning Star Drive, Ste. A, Sonora, CA 95370

| T H E PA I N PRACT ITION ER | A U G U S T / S E P T E M B E R 2 0 1 6

ACADEMY BOARD OF DIRECTORS President Joanna Katzman, MD, MSPH Past President Robert A. Bonakdar, MD, FAAFP Vice President W. Clay Jackson, MD, DipTh Secretary Paul Christo, MD, MBA Treasurer Kevin T. Galloway, BSN, MHA, Colonel, US Army (Retired) Directors-at-Large Alfred V. Anderson, MD, DC John Garzione, DPT Christian D. González, MD Gerald Q. Greenfield, Jr., MD Michael Kurisu, DO, ABIHM Arthur S. Roberts, DDS, MD Liaison to the Board Maggie Buckley ACADEMY STAFF Executive Director Robert Twillman, PhD, FAPM Director of Professional Development Debra Nelson-Hogan Director of Business Development and Brand Management Tarah Remington-Brown Director of the State Pain Policy Advocacy Network (SPPAN) Amy Goldstein, MSW Accounting Director Kristin Taylor Assistant Director of Education Cathleen Coneghen SPPAN Assistant Director for Legislative and Regulatory Affairs Katie Duensing, JD Member Services Manager Whitney O’Donnell Account Managers Rosemary LeMay, Sheila Miller Professional Development Project Manager MacKenzie Davis Office Manager Karen Hebert

THE PAIN PRACTItiONER STAFF AND CONSULTANTS Editor Debra Nelson-Hogan Advertising and Sales Sheila Miller Managing Editor Cathleen Coneghen Clinical Editor Christine Rhodes, MS Art Director Amy Bothwell Copy Editor Rosemary Hope The Pain Practitioner is published by the Academy of Integrative Pain Management, 975 Morning Star Drive, Ste., A, Sonora, CA 95370, P: 209-533-9744, F: 209-533-9750, Email: aapm@aapainmanage.org, website: www. aapainmanage.org. Copyright 2007 American Academy of Pain Management. All rights reserved. Send correspondance to: Debra NelsonHogan at dhogan@aapainmanage.org. For advertising opportunities, media kits, and prices, contact: Sheila Miller at 209533-9744, or smiller@aapainmanage.org The Pain Practitioner is published by the Academy of Integrative Pain Management solely for the purpose of education. All rights are reserved by the Academy to accept, reject, or modify any submission for publication. The opinions stated in the enclosed printed materials are those of the authors and do not necessarily represent the opinions of the Academy or individual members. The Academy does not give guarantees or any other representation that the printed material contained herein is valid, reliable, or accurate. The Academy of Integrative Pain Management does not assume any responsibility for injury arising from any use or misuse of the printed material contained herein. The printed material contained herein is assumed to be from reliable sources, and there is no implication that they represent the only, or best, methodologies or procedures for the pain condition discussed. It is incumbent upon the reader to verify the accuracy of any diagnosis and drug dosage information contained herein, and to make modifications as new information arises. All rights are reserved by the Academy to accept, reject, or modify any advertisement submitted for publication. It is the policy of the Academy to not endorse products. Any advertising herein may not be construed as an endorsement, either expresed or implied, of a product or service.

notes from the field

What’s in Our Toolbox? By Robert Twillman, PhD, FAPM, Executive Director

“I suppose it is tempting, if the only tool you have is a hammer, to treat everything as if it were a nail.” —Abraham Maslow

Maslow’s Law of the Instrument epitomizes the popular view of mainstream pain management today, with the hammer representing opioid analgesics. In this view, when a clinician encounters someone with pain, the first, and often only, response is to write an opioid prescription—whether that is the right thing to do, or not. It’s like asking a handyman to come to your house to fix several unspecified problems, and having him show up carrying only a hammer—he may be able to fix a few things, but if he tries to fix everything with that hammer, he’s going to end up creating damage, perhaps enough to outweigh the good done in fixing things. Too often, I fear, there is a good deal of truth in this perception. It’s not that well-meaning clinicians have consciously decided that every pain condition is a nail needing a hammer. A combination of forces has produced a hammer-loving cadre that now confronts a regulatory environment bent on taking away that hammer. A couple of decades ago, many multidisciplinary, integrated pain management clinics existed, and they successfully used a variety of tools to repair the broken quality of life experienced by many people with chronic pain. However, third-party payers decided that it would be a lot cheaper to only pay for one tool, the hammer, rather than to also pay for saws, screwdrivers, drills, wrenches, and the like. Pharmaceutical manufacturers, whether intentionally or not, spread the news that, because the hammer worked when it was used on the nail we called “cancer pain,” it should also work when a screw known as “non-cancer pain” was presented. And, in the interest of keeping the flow of patients, and therefore revenues, flowing through the exam room in an unimpeded manner, many clinicians noticed that

they could much more quickly drive a nail with a hammer than drive a screw with a manual screwdriver. Consequently, opioid prescribing shot through the roof, with the attendant harms and benefits we have witnessed over the past few years. Reacting to this, policymakers have decided that they need to take the hammers away from clinicians. They have done this by issuing guidelines saying that non-pharmacological treatments and non-opioid medications should be used before opioid therapy is started—the equivalent of a sticker on the hammer saying that you shouldn’t use it until you’ve tried a few other tools. Sometimes, they have said that opioid prescriptions, for both acute and chronic pain, should be limited to a certain number of dosage units and/or a certain daily dose, rather like saying that you are allowed to whack your hammer’s target once or twice with moderate force, but then you have to stop and do something else. And some have even tried to outlaw certain types of hammers, by outlawing certain opioid analgesic preparations. The problem, though, is this: if the handyman has his hammer taken away, the homeowner who called him is left with problems that need to be fixed, and a handyman with no ability to help. As policymakers have steadfastly worked to limit the use of opioids through restrictive legislation and regulation, they have not done anything to expand the variety of tools available to us, leaving people with pain to suffer their broken quality of life and clinicians with no means of helping.

Integrative Pain Management: Using the Full Toolbox The integrative approach to pain management espoused by our academy requires availability of a wide variety of tools (pain treatments), and then, in consultation between the handyman and the homeowner (primary care provider and person with pain), choosing the set that will best address the needs identified in the initial assessment. Some-

times, the handyman will be able to use the available tools adequately himself, but sometimes he must act as a general contractor and call in master plumbers and electricians, finish carpenters, roofers, and other specialists (e.g., acupuncturists, chiropractors, psychologists, etc.) to use the available tools in the most expert manner possible. To make this integrative approach a reality, we need our primary care colleagues to be adequately edu-

cated about using a variety of tools, and to know when to call for the experts to use those tools. We need an adequate supply of specialists available to respond to those calls. And, most of all, we need to be sure that the homeowner/person with pain can afford to have those specialists use their tools (i.e., we need to be sure they have adequate insurance coverage for those treatments). That is a tall order, but it clearly speaks to the Academy of Integrative Pain Management’s mission to provide education and advocacy that will fill the toolbox and teach how to use each tool. Whether you are the handyman or the master electrician, we need you to help us achieve that mission by learning, teaching, and advocating for the integrative pain management model. There is a lot of work to be done, but if we all pitch in, I’m confident we can have everything shipshape before too long.

THE PAIN PRACTITIONE R

Bob Twillman, PhD, is the executive director for the Academy of Integrative Pain Management. Dr. Twillman is responsible for overseeing federal and state pain policy developments and advocating for those supporting an integrative approach to managing pain. He also serves as Chair of the Prescription Monitoring Program Advisory Committee for the Kansas Board of Pharmacy.

| VOLUME 26, NUMBER 4 |

MEMBERSHIP

Yesterday, Today, and Tomorrow

The Academy of Integrative Pain Management & the National Pain Strategy National Pain Strategy

When the American Academy of Pain Management, now the Academy of Integrative Pain Management (AIPM), was formed 27 years ago, the founders believed passionately that their multidisciplinary, biopsychosocial, multimodal approach to caring for patients in pain produced the best outcomes. They probably did not expect however, that it would take nearly three decades for the rest of the medical and scientific community to catch up. Earlier this year the National Pain Strategy (NPS) focused like a laser on advancing integrative pain care, so it is not surprising that many of its recommendations and plans are mirrored in the ongoing work and future plans of AIPM.

Basic Education, Skills Training, and Performance Improvement AIPM has long recognized the need for improved education and training of clinicians in the provision of integrative pain care, and has been a leader in In implementing providing continuing education opporthe National Pain Strategy, the lead- tunities in this realm. AIPM’s strategic and operating plans are rooted in the ership agencies responsible seem fundamentals of traditional clinical practice—expanding the evidence to have, in AIPM, an ideal partner. base, adding to practitioners’ pool of Not only has the knowledge, teaching new clinical skills, AIPM pioneered and continuously improving perforintegrative pain mance and outcomes. Most recently, care, it has the AIPM has invested in an exponenperfected it! tial expansion of its clinical education and communications programs.

The Pain Practitioner, the AIPM award-winning publication, has been re-engineered to enhance readership and the frequency was increased from

four issues per year to six. For those who prefer the tactile reading experience a physical magazine affords, the print circulation was increased this year to 15,000. In addition, a new electronic version of the magazine is now available on-demand, online with each issue’s contents communicated to more than 55,000 multidisciplinary clinicians. The popularity of the e-magazine is rapidly increasing thanks to the ability for “deep dive” links from articles to additional resources or enhanced content such as video interviews with speakers, slide-audio presentations, downloadable pdfs, and other valuable content.

The Pain Care Learning Center serves as a one-stop educational resource for all clinicians who care for people with pain, with topics covering the range of traditional as well as complementary and alternative treatments for pain. The National Pain Strategy specifically calls for such a portal. In October, nearly 60 hours of accredited continuing education content from the 27th Annual Meeting will be posted to the Pain Care Learning Center. In 2017, the AIPM hopes to solicit educational content from other accredited providers, exponentially expanding the offerings.

Team Pain Care™ While newer training models emphasize interprofessional education, AIPM recognizes most of these programs focus on team-based education involving medical and nursing students, and that some also include allied health professionals such as physical and occupational therapists; very few of them include social workers and clinical health psycholo-

| T H E PA I N PRACT ITION ER | A U G U S T / S E P T E M B E R 2 0 1 6

gists, despite the importance of social and behavioral determinants of health, and virtually none of them pair “traditional” health care professionals with “complementary and alternative” health care professionals. While the NPS has focused almost entirely on physicians and, to a lesser degree, nurses, AIPM recognizes that there are many types of clinicians who care for people with pain, as reflected by the fact that 40% of our members are chiropractors, acupuncturists, massage therapists, dentists, podiatrists, and naturopathic physicians, and strives to provide appropriate education for all of them.

Service Delivery, Reimbursement, Policy & Advocacy More than any other pain organization, a core mission of AIPM is to ensure that people with pain are provided optimal integrative pain care, with the understanding that achieving that goal requires multiple strategies. The executive director and two full-time staff members work tirelessly in the exploration of reimbursement models that focus on rewarding the achievement of the goals of pain care, rather than rewarding the number of interventions provided. An integrative model of care has its costs “front-loaded” and its benefits “back-loaded,” making a longterm view of outcomes vital if the true value of this treatment approach is to be seen. Providing a pill will always be less costly than providing a multidisciplinary assessment and treatment protocol, unless long-term outcomes such as cumulative health care delivery costs, long-term disability vs. productivity, and impact of adverse effects (such as

MEMBERSHIP

substance abuse) are considered. In addition to its focus on getting integrative care reimbursed, AIPM’s policy and advocacy team monitors hundreds of pieces of legislation and proposed regulations that all can affect, positively or negatively, the ability of clinicians to deliver integrative pain care. Popular areas for policymakers to address include requirements for continuing education in order to renew a clinical license; requirements to query prescription drug monitoring programs prior to prescribing a controlled substance; prescribing guidelines promulgated by licensing boards, health departments, or even by legislators themselves; and many others. AIPM’s policy and advocacy staff evaluates all of these proposed policies, and contacts policymakers when it determines that a particular policy warrants support, opposition, or amendment, always in keeping with the goal of producing balanced policies that support integrative practice. These efforts have resulted in substantial changes to many state and federal policies, and AIPM is becoming known in the medical community as the go-to source for pain management policy analysis and response.

EXPANDING THE EVIDENCE BASE If the challenges inherent in generating prospective, randomized controlled trials to study the efficacy and safety of pain medications are substantive, then they are overwhelming relative to studying integrative care interventions. As the only major organization that has advocated its own special brand of effective, safe, and sane pain care for nearly 30 years, AIPM is uniquely qualified to quantify some of that experience

and add it to the body of knowledge clinicians so desperately need. While it is true that prospective longitudinal research might be the gold standard, AIPM believes that mining of the very rich data contained in large electronic medical record databases could provide many of the most important answers we need, and do so in a fraction of the time and at a fraction of the cost involved in collecting prospective data. The NPS recognizes the research challenges and AIPM hopes to provide a light at the end of the tunnel with its pragmatic approach to evidence generation that has been under development in recent years but has not yet been funded. AIPM hopes to persuade Interagency Pain Research Coordinating Committee (IPRCC), National Institutes of Health, and other relevant agencies to increase their attention to the importance of innovative and pragmatic clinical and translational research as a means of more rapidly achieving the goal of providing high-quality integrative pain care for everyone with chronic pain. The AIPM also plans to work with relevant federal agencies to increase support for research into the benefits of pain treatments that are typically labeled as “complementary and alternative.” Many of these treatments have strong anecdotal support and weaker, but existing, research support, especially when used to treat certain people and certain painful conditions, yet payers are reluctant to cover these treatments because there is insufficient evidence of their efficacy. Note that there is rarely any concern about the safety of these treatments, unlike there is with pain management procedures and medications. Note also that the

Member Exclusive Opportunity – Share Your Insights Now AIPM recently formed five new Shared Interest Groups (SIGs). They include: • Federal Medicine • Nutrition in Pain Management • Pain Rehabilitation • Palliative Care • Behavioral Health

NATIONAL PAIN STRATEGY: A Comprehensive Population Health-Level Strategy for Pain DIAGNOSTIC CLUSTERS FOR POPULATION PAIN RESEARCH 1. Back pain 2. Neck pain 3. Limb/extremity pain, arthritis disorders (including osteoarthritis and joint pain) 4. Fibromyalgia and wide-spread muscle pain 5. Headache 6. Orofacial, ear, and temporomandibular disorder pain 7. Abdominal pain and bowel pain 8. Chest pain 9. Urogenital, pelvic, and menstrual pain 10. Fractures, contusions, sprains and strains 11. Other painful conditions (sickle cell disease, complex regional pain syndrome, systemic lupus erythematosus, acquired deformities [excluding spinal disorders], spinal cord injury, Lyme disease, and neuropathic pain.) Note: Cancer pain is included here, but relevant diagnostic codes need to be identified.

evidence supporting the benefits of these “traditional” interventions is really no stronger than that supporting the complementary and alternative interventions. Support for patient registries focused on true integrative care models is extraordinarily important to AIPM, as is support for demonstration projects through Medicare, Medicaid, and commercial payers. In implementing the National Pain Strategy, the leadership agencies responsible seem to have, in AIPM, an ideal partner. Not only has the AIPM pioneered integrative pain care, it has perfected it! And, if these focus activities for the AIPM are any indicator, AIPM is going to be essential to the successful implementation of the NPS long into the future.

SIGs are for like-minded volunteer leaders to come together with the Academy to guide essential education, to share case studies and improvement outcomes with their peers, to recruit members like themselves to the association, and to craft white papers. The SIGs will meet face-to-face during our 27th Annual Meeting. Not a member? If you’d like to participate in the SIG meeting during the Academy’s Annual Clinical Meeting, join us on Saturday, Sep. 24 from 2:00-4:00pm CT to learn more about what these important groups will be doing in 2017. TO PARTICIPATE IN A CURRENT SIG, EMAIL US AND INDICATE YOUR INTEREST: MEMBERSHIP@AAPAINMANAGE.ORG

THE PAIN PRACTITIONE R

| VOLUME 26, NUMBER 4 |

MEMBERSHIP

Academy Forms and Staffs New Business Development and Brand Marketing Department By Bob Twillman, PhD, Executive Director, AIPM

As a key part of its strategic restructuring, the Academy has created a Business Development and Brand Management Department, which includes a seasoned membership management team: Tarah Remington Brown and Whitney O’Donnell. Tarah Remington Brown, Director of Business Development and Brand Management, will be responsible for member services, marketing, brand management, and communications. She will report to Bob Twillman, PhD, Executive Director of the AIPM. Ms. Remington Brown, based in Kansas City, Missouri, has worked in association management, primarily in membership development and brand marketing, for 17 years. She has presented on brand management to a variety of audiences and served on councils, committees, and task forces Tarah Remington Brown, Director of in her industry, focusing on research, Business Develop- meeting planning, volunteer management and Brand ment, and content creation. Management, and After earning a degree in marketWhitney O’Donnell, ing with an emphasis in advertising Member Services and promotion from Missouri State Manager. University she “cut her teeth” working in health care associations, beginning her career at the American Academy of Family Physicians. Ms. Remington Brown has worked with optometrists and certified optometric staff, brand marketers and advertising agencies, and administrative and office professionals. You can connect with her at tremingtonbrown@aapainmanage.org or on Twitter @tarahlbrown. Whitney O’Donnell has joined the AIPM as Member Services Manager. For the past seven years she has worked for a health care association serving nursing home administrators and is excited to meet and serve a new membership base. She brings a wealth of knowledge in growing, maintaining, and engaging members as well as managing overall membership satisfaction. Ms. O’Donnell, based in Cleveland, started her professional career in business management with Wells Fargo Fi-

nancial. With increased sales and drive, she quickly became a branch manager where she managed a small office, which included hiring, training, and day-to-day operations. Ms. O’Donnell developed a passion for recruiting, and therefore continued her career working as a division director at Robert Half International. Ms. O’Donnell then developed an interest in the nonprofit, association sector. For the past seven years, she managed the membership database, retention, and member communications at the American College of Health Care Administrators (ACHCA). She also brings experience in association fundraising, event planning, and database migration. Ms. O’Donnell graduated from John Carroll University in Cleveland with a degree in business administration. Feel free to reach her at wodonnell@ aapainmanage.org. She will report to Ms. Remington Brown. Together, they will offer consistency to the Academy’s membership processes and updates to member benefits, features, and services. This includes improved customer experience with the Academy’s website, access to newly forming shared interest groups, and members-only online forums where interest groups can meet and

The Academy’s new membership team pledges to bring members cutting-edge features and benefits.

their Academy. They are also identifying ways for members to gain access to industry content in a streamlined, on-demand way as a complement to our Learning Management System. The new membership team at the Academy pledges to bring members cutting-edge features and benefits, highlighting all best practices in integrative pain management.

Contributors Donations support the vital work of the Academy’s policy and advocacy efforts. We would like to thank the following contributors: Amelia L. A. Tabuena, MD Andrejs Strauss, MD Daniel Wynn, MD Gwinn Murray, MD Harry Manuel Sanchez-Torres, MD James S. Wike, MD Jeffrey C. Vernon, DDS Joan Riemer-Elser, OMD Keith Thompson, CRNA Klee Steven Bethel, MD Lee Ann Rhodes, MD Mazyar Jasbi, DC Rafael V. De La Riva, MD Richard Kulwin, DDS Robert G. Salazar, MD Roberta Jane Hollenbeck Rodger K. Garrett, MD Segundo Gabriel Roncal, MD Stephen A. Kibrick, PhD Donations may be tax deductible as an ordinary business expense. If you would like to donate in support of our policy and advocacy please contact the Academy at 209-533-9744 or aapainmanage.org.

In Memory

collaborate, virtually. Additional plans include developing opportunities for members to create content and share published articles related to integrative pain care, and identifying and highlighting a Member of the Month, providing the Academy the chance to show the stars in our industry. They will conduct regular member feedback surveys so we can hear what our members want from

| T H E PA I N PRACTITION ER | A U G U S T / S E P T E M B E R 2 0 1 6

We honor the memory of the following deceased members: Christopher M. Loar, MD Michael P. Moore, MD Paula M. Sandler, MD Edward Chorette, MD John Wood, MS, BS Peter J. S. Koo, PharmD

Chronic Pain & Recovery Center A treatment program with proven results for patients with chronic pain and co-occurring mental illness or addiction. â&#x20AC;˘ 80% of patients who completed our program were either completely off opioids at discharge (63%) or on agonist therapy (17%) â&#x20AC;˘ Patients reported a 24% mean reduction in reported pain To get more information about our treatment outcomes, please call 866.542.4455.

www.silverhillhospital.org

education

Chronic Pain a Key Focus of the NCCIH Research Strategy By Debra Nelson-Hogan, Director of Professional Development

The National Center for Complementary and Integrative Health (NCCIH), the leading federal agency for research on integrative and complementary health practices, recently released its 2016 Strategic Plan, one key element of which involves research into integrative pain management therapies. The NCCIH has a budget of $125 million, and approximately 30% of that is going into pain research. Bob Twillman, PhD, executive director of the Academy, spoke with Josephine P. Briggs, MD, director of the NCCIH, about the impact that this plan and the research to support it will have on chronic pain.

Josephine P. Briggs, MD, director, National Center for Complementary and Integrative Health (NCCIH)

Dr. Twillman: Can you give us overview of the recently released NCCIH 2016 Strategic Plan and how it applies to pain in particular? Dr. Briggs: The strategic plan is centered around five main objectives and supported by six scientific research priorities. Our second objective, Improve Care for Hard-to-Manage Symptoms, includes pain, anxiety, and depression, and the nonpharmacologic management of chronic pain is one of our top research priorities (see sidebar). You know that pain has very

high economic and societal costs, and is the condition most used for complementary and integrative health approaches. We have developed a very practical portfolio dealing with the challenges of modifying and improving the care of people with pain, and the more we learn from people practicing integrative pain management, the more we can make our portfolio valuable and, indeed, pragmatic—that is, testing complementary and integrative health interventions in “real world” settings. The strategic plan poses a few of the questions that we think are not fully being addressed by the current portfolio of research that we’re supporting. We have funded a number of studies on complementary modalities like yoga and meditation, and we’re clearly learning something about the efficacy of these approaches. Results of one recent study were published last March in JAMA (1) showing that mindfulness-based meditation and cognitive behavioral therapy resulted in greater improvement in pain, with better functional outcomes, compared to usual care. Results from another study, published in The Journal of Neuroscience

NCCIH 2016 Strategic Plan: Exploring the Science of Complementary and Integrative Health Objectives 1. Advance Fundamental Science and Methods Development 2. Improve Care for Hard-to-manage Symptoms 3. Foster Health Promotion and Disease Prevention 4. Enhance the Complementary and Integrative Health Research Workforce 5. Disseminate Objective Evidence-based Information on Complementary and Integrative Health Interventions Top Scientific Priorities • Nonpharmacologic Management of Pain • Neurobiological Effects and Mechanisms • Innovative Approaches for Establishing Biological Signatures of Natural Products • Disease Prevention and Health Promotion Across the Lifespan • Clinical Trials Utilizing Innovative Study Designs to Assess Complementary Health Approaches and Their Integration into Health Care • Communications Strategies and Tools to Enhance Scientific Literacy and Understanding of Clinical Research

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(2), found that mindfulness-based meditation reduced pain without actually activating endogenous opioids. This study suggests that combining mindfulness-based meditation and pharmacologic/nonpharmacologic pain-relieving approaches that rely on opioid signaling may be particularly effective in treating pain and reducing the requirement for opioids. We have very few studies that measure this, and it’s an example of research we would like to see in the future. Dr. Twillman: Can you tell us about your partnership with the Veterans Administration and the Department of Defense? Dr. Briggs: We are about to launch a partnership with investigators in Veterans Administration facilities and perhaps in DOD facilities looking at pragmatic approaches to improving pain management in veterans and military personnel. When it comes to problems with chronic pain this is a very vulnerable population. In addition, our intramural program focuses entirely on how processing and central mechanisms in the brain for modifying pain are influenced by emotional states or other variables, such as long-term yoga practice. That portfolio is about understanding the basic pathways of pain and how mental states and mental practices might modify them. Dr. Twillman: That’s really fascinating research. And I think Dr. Catherine Bushnell, who is going to be a keynote speaker at our annual meeting in September, has done some of that research. Dr. Briggs: Yes, Dr. Bushnell is the scientific director for our intramural program and is doing really a great job in building a team of terrific young scientists who will expand this part of our investment. Dr. Twillman: So now that you have the strategy, what is the process of moving from point A, where we’ve identified the needs, to point B, the outcomes of the research? What

education

are the mechanisms to carry out the strategy now? Dr. Briggs: One of the things we are learning is that we want to move away from relying only on the classic randomized efficacy trial, in which you compare a complementary mind-body approach with a time and attention control, to studies that look more at integrative approaches and potentially the effect of several different modalities on outcomes. However, we are also eager to maintain rigor while we do that, which means using the well-established pragmatic trial methodology. One kind of pragmatic trial occurs in the setting of the large health care systems. One that’s going on right now is a study led by Dr. Lynn L. DeBar in several Kaiser facilities, where practitioners are randomized—half work as they have always done, and the other half have trained coaches to help with patient care. We will see whether the outcomes in practices that have a more complex set of integrative modalities available are, in fact, measurably improved. But that’s the kind of work that I think is desperately needed to really understand what approaches can be scaled in this significant way. While I’m an enthusiast for things

like meditation and yoga I don’t necessarily believe that by themselves these methods will make pain go away. They are part of a whole strategy to help people take more charge of their lives and their care and to move the power of deciding treatment to the person, not the physician. Dr. Twillman: Right. That fits very well with our focus and what we teach and what we advocate for. It’s always patient centered and taking advantage of a whole variety of interventions. However, based on groups, such as the Interagency Pain Research Coordinating Committee (IPRCC), it appears that strategic plans to define and conduct research are dominated by allopathic practitioners—physicians, nurses, and a few psychologists. You might look at the so-called “gang of eighty” that crafted the National Pain Strategy. There was only one person I can identify as an integrative medicine practitioner. Do you see any opportunities for us to broaden our representation within groups like the IPRCC? Dr. Briggs: I think it’s a great suggestion and I welcome suggestions from your organization. We do need to strengthen our community of integra-

tive practitioners who are active in the policy-making. Dr. Twillman: I think the other big barrier that we run into of course is the reimbursement barrier and the extent that it is based on perceived lack of evidence. Dr. Briggs: I’m very well aware that the reimbursement issues are incredibly important. Our role here is to make sure that there’s a research agenda that will provide the evidence needed for policy setting, and that includes reimbursement policies. Dr. Twillman: I appreciate you taking the time to talk with me today and I hope that we can work together in the future to support your strategic plan and other important pain programs.

References 1. Cherkin DC, Sherman KJ, Balderson BH, et al. Effect of mindfulness-based stress reduction vs cognitive behavioral therapy or usual care on back pain and functional limitations in adults with chronic low back pain: a randomized clinical trial. JAMA. 2016;315(12):1240-1249. (http://jama.jamanetwork.com/article. aspx?articleid=2504811) 2. Zeidan F, Adler-Neal AL, Wells RE, et al. Mindfulness-meditation-based pain relief is not mediated by endogenous opioids. J Neurosci. 2016;36(11):3391-3397.

Thank you to our Corporate Council Members!

Academy of Integrative Pain Management CORPORATE COUNCIL MEMBERSHIP Contact Tarah Remington Brown, tremingtonbrown@aapainmanage.org to become a Corporate Council Member today!

THE PAIN PRACTITIONE R

| VOLUME 26, NUMBER 4 |

PROFESSIONAL DEVELOPMEnT

New Name, Same Game

After 27 years, John Garzione, DPT, is still fired up about the Academy By Debra Nelson-Hogan, Director of Professional Development

John Garzione, DPT, has been a member of the Academy since 1989 and was elected to the Board of Directors in 2015. He has over 40 years’ experience as a physical therapist. He is the owner of Chenango Therapeutics in Norwich, New York, an outpatient physical therapy clinic that specializes in the treatment of a variety of persistent pain conditions.

John Garzione, DPT, has been a member of the Academy since 1989 and was elected to the Board of Directors in 2015.

TPP: I wanted to talk to you because you have been with us from the beginning and now you are a board member as well. Why did you join the Academy is 1989? Dr. Garzione: I saw a flier announcing a new group called the American Academy of Pain Management and I liked that it was interdisciplinary, which was a totally new concept. You have to understand that I’m here in central New York about “six miles north of hell.” In 1989, no one here was doing what I was doing (managing chronic pain) and I didn’t know if I was doing it right. I read and did a lot of research to determine how to treat patients. When I went to my first Academy meeting I decided that this was a meeting that I would go to forever.

TPP: Why? Dr. Garzione: Every year it sparked my interest and I was really, really excited. I came back invigorated. I met some great physicians who were doing cutting-edge treatments and I would send them my difficult-to-treat patients. Also, I never felt that I was “just a PT.” TPP: Why did you become interested in chronic pain? Dr. Garzione: I realized that some people just don’t get better and there just has to be something else that we can do. When I saw my first fibromyalgia patient I tried to figure out what else was going on. She had been ushered out of several doctors’ offices. They thought she was crazy, or lazy, but she was in pain. I took an interest in her. My turning point was realizing that we are doing a lousy job with some patients because we are not looking at what else is going on with them. What do we not understand? TPP: You have commented a lot about research and keeping up with the science. Was this your motivation for starting a shared interest group (SIG) with the Orthopedic Section of American Physical Therapy Association (APTA)? Dr. Garzione: Ultimately, yes. We got approval from the APTA to do a SIG on pain management in 1995 and at the beginning we would do a presentation on pain at the annual meeting. When I became president in 2007, I wanted to distribute research to the members. Let’s face it, we can’t read everything and we can’t know everything, so we shared articles. We did blast e-mails to make this a collaborated effort, but unfortunately we didn’t have one person dedicated to doing the blasts. We wanted to distribute new research and, interestingly enough, years ago we wanted to do a program on nutrition for our pain SIG. The members thought it was an awful idea, and then five years later there were a lot of other presentations on nutrition. We were just ahead of our time. TPP: Can you take that experience and use that to help you guide the

Physical Medicine and Rehabilitation SIG that you are co-chairing for the Academy? Dr. Garzione: Yes, I’m chairing that SIG with Roger Mignosa, DO, a knowledgeable young physician based in San Diego. This multidisciplinary SIG will collect a knowledge base of the “hands-on professions” for the distribution of current information of nonpharmacological rehabilitation techniques, such as electrotherapy, exercise, mobilization, manipulation, and biomechanical corrections. These modalities have been shown to reduce pain perception, improve blood flow, increase muscle tone to decrease disuse pain as well as help reset the nervous system using the concept of neural plasticity. It is pretty exciting. We hope that it will spark more interest in the SIG among other professionals. I would particularly like to see more physical therapists join. TPP: Do you think PT is well versed in treating chronic pain? Dr. Garzione: No, but it goes beyond only physical therapists. One of our local physicians had referred patients to us for years and he is now working as a hospital administrator. He asked if we would partner with them because they were unsure about treating people with chronic pain. He really needed a pain management specialist. It’s a sad state of affairs when the PT is coordinating care, but I’ve been doing it for years. TPP: Your SIG focuses on multidisciplinary clinicians practicing nonpharmacological rehabilitation techniques which represent some key areas in integrative medicine. That being said, how do you feel about the Academy name change? Dr. Garzione: My immediate reaction was, “Why change it? We already have a really good moniker of what we do,” and then I thought, “No, it really doesn’t tell what we do.” We are integrated in our pain management and we are the only group that pulls everybody together. This has been the part that has had me so fired up with the Academy from the beginning.

ADVOCACY

State Pain Policy Advocacy Network (SPPAN)

Working for (and with!) You to Make Integrative Pain Care Attainable for All By Katie Duensing, JD, SPPAN Assistant Director for Legislative and Regulatory Affairs

As a project of the Academy of Integrative Pain Management, SPPAN aims to promote optimal, personcentered care by advancing effective pain policy, guided by the mission of advancing a safe and effective, comprehensive, multidisciplinary, and integrated approach to delivering pain care. While we have been advocating for this type of care for years, getting the attention of powerful policymakers who are heavily lobbied by the insurance industry and pharmaceutical manufacturers has been difficult— until now.

Policies across the nation are beginning to focus on integrative pain care In the past year, we have seen an unprecedented shift in the minds of policymakers across the nation as they seek to find safe and effective alternatives to opioid analgesics. Numerous states have considered and/or implemented policies that either 1) urge practitioners to consider utilizing alternatives to opioid analgesics (illustrating their potential willingness to explore policies that may make those alternatives a feasible option) or, 2) expand access to, and affordability of, integrated and multidisciplinary pain management. Even the Centers for Disease Control and Prevention, in their recently released Guideline for Prescribing Opioids for Chronic Pain, stated as the very first sentence of their first recommendation that “Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain.” Policymakers are clearly expressing a desire to explore alternative methods of pain management, but how they ultimately improve pain policy (and more pointedly, how effectively they improve pain policy) is yet to be seen. Most certainly, developing optimal policies will be best accomplished with the active participation of qualified experts in

integrative and multidisciplinary pain management.

Thinking creatively to improve the state of pain care SPPAN, with the support of our scores of pain-related partner organizations representing patients, clinicians, health systems, and others, stands ready to play an active role in ensuring that policymakers are truly making meaningful improvements to pain care in the United States, not by merely shifting away from certain treatments, but by shifting toward a health care system that is able to optimally and affordably treat patients’ pain through the use of all appropriate treatments, provided by an integrative care team. We have several ideas for improving access to, and affordability of, integrative pain care, but each will require the coordinated and thoughtful participation of concerned stakeholders to show policymakers that new and innovative ideas are worthy of implementation. We believe that nonpharmacological treatments for pain should have insurance coverage parity with pharmacological treatments for pain, enabling patients to affordably access treatments such as acupuncture, massage therapy, chiropractic care, physical therapy, occupational therapy, cognitive behavioral therapy, and more. We believe that no health care practitioner operating within his or her scope of practice should be discriminated against by insurers. We believe that network adequacy should include adequate complements of clinicians providing specialized treatments for pain. We believe that prior authorization and step therapy policies shouldn’t stand in the way of patients accessing nonpharmacological treatments. We believe it is vital that when statutes, regulations, or guidelines urge that alternative treatments be considered in lieu of opioid analgesics, that those same policies ensure that clinicians are armed with the proper education and training to know how to safely

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and effectively treat their patients’ pain via alternate methods that are truly obtainable by their patients. In essence, we believe that patients must have affordable access to a wide array of pain management options and to an integrative care team willing to work together on the patient’s behalf.

Ensuring optimal integrative pain care policies are implemented is a team effort How do we make such grand plans a reality? With YOUR support. Policymakers often tell us that they haven’t made a change because no patients or clinicians have asked for such a change or expressed a concern with an existing policy. We can show them all the statistics in the world explaining why they should take action, but what truly makes a difference is when health care practitioners take the time to reach out to their representatives to express a concern and offer a solution based on their medical expertise. If you are as concerned with advancing integrative pain care as we are, reach out to us! Regardless of your past advocacy experience, your voice is incredibly valued, and we would love to work with you to find how best to make your perspective heard. To learn more about SPPAN and all that we do, visit us on the web at www.sppan.aapainmanage.org. To talk about how you can do your part in advocating for improved pain policies, contact Amy Goldstein, SPPAN Director, at agoldstein@aapainmanage.org. Katie Duensing, JD, is the Assistant Director for Legislative and Regulatory Affairs for the State Pain Policy Advocacy Network, a project of the Academy of Integrative Pain Management. She monitors, analyzes, and works to improve pain-related policies from every jurisdiction across the nation, actively engaging with policymakers to help shape optimal, person-centered pain policies.

MEMBER profile

Better Education and Mentorship to Advance Pain Management in Primary Care By Debra Nelson-Hogan, Director of Professional Development

Robert L. Rich, Jr., MD, a family practice physician in Elizabethtown, North Carolina, chaired the American Academy of Family Physicians’ (AAFP) opioid and pain management workgroup for the Academy’s Commission on Health of the Public and Science. He believes education and mentorship are vital in the challenge to resolve the dual public health crisis of undertreatment of pain and addiction to opioids. TPP: What does pain management look like from the family practice perspective? Dr. Rich: I’m a family physician from southeastern North Carolina and I practice in a rural area. Statistically, there’s a higher incidence of pain issues and opioid prescribing in a rural area, and my area in particular has a very high incidence of pain issues and opioid prescribing on a per capita basis. I also work as a regional medical director for Community Care of North Carolina, which is the nonprofit that administers the state’s Medicaid program. TPP: Why do rural areas have a higher incidence of pain and opioid abuse? Dr. Rich: Two things come to mind. Number one, in rural areas as you can imagine, there are a lot of people employed in manual labor and other occupations where they may be at risk of injuries, particularly back and joint pain which can turn into chronic musculoskeletal pain. And unfortunately, in rural areas there are a lot of uninsured patients or patients with limited medical coverage. Many don’t have access to a lot of the adjunctive pain management therapies that we would like to offer. Opioids, which are relatively inexpensive and available, may be the only treatment that patients can afford. Even if we can refer patients to a pain management clinic, there are other barriers, such as transportation. Also, as you know, pain management education in primary care has left a lot to be desired. I’ve been in practice now almost 30 years, and my education in pain management came from observing my faculty mentors who prescribed

opioids for pain control in the absence of any defined guidelines. If they prescribed opioids, that is also what you learned to do. TPP: How do you feel about the CDC guidelines? Dr. Rich: In full disclosure, I represented AAFP on the core expert group and I was in that initial phase of the evaluation of the guidelines. I think the guidelines are a good tool for managing the opioid naive patient. However, many of my patients have been on opioids for years and neither the CDC guidelines nor a lot of other guidelines do much to help physicians in terms of addressing those patients. They may be on high dose opioids and how do you manage them? Do you taper and if so, how? There is a lot of controversy about the 50 milligram morphine equivalent (MME) maximum daily dose, and the evidence used to set that level. So the 50 MME, while not set in stone, is certainly a conversation point for patients getting that high up on the opioid ladder. Should I not consider using other therapies at that point? So while imperfect and while we certainly raise concerns about the strength of the recommendations versus the evidence that was there, they do have some utility in practice. TPP: What percentage of your practice is dedicated to pain patients? Dr. Rich: Of the patients who come through my door, some days, easily 50% of them have pain issues or may be on pain medications in addition to all their other medical problems. TPP: So do you refer patients to pain management specialists? Dr. Rich: I refer to pain management specialists when I see an escalation of the pain beyond what I’m comfortable treating or if I see additional factors which I think may be modifying that pain response. I also refer patients to substance abuse addiction specialists. TPP: I was looking at a position paper from the AAFP in 2012 that said traditionally among family practice

clinicians there is a negative reaction to chronic pain patients. What can we do about that? Dr. Rich: I would say, anecdotally, that negativity that you allude to actually seems to be growing with all the attention that we’ve devoted to opioids. I see fewer physicians who are willing to manage patients on opioids because of the fear that they are doing something wrong. The best way to deal with that, again, is education and mentorship. We know if physicians have the example of a strong mentor who can balance the needs for managing a patient’s pain with all classes of medications and therapies, including opioids, then they’re much more comfortable and willing to manage and treat pain appropriately. In addition, we need to be strong leaders and keep talking about the issue, looking for better solutions for managing the pain crisis from both the pain management and the family practice platforms. Our role is to get the message out that we have the tools and can take care of these patients, if done correctly.

Academy Annual Meeting: Robert L. Rich Jr., MD, will participate in the Advocacy lunch session, From Policy to Practice: How the CDC Guidelines Play out in Primary Care, on Friday, September 23, in San Antonio.

Help your patients for the week ahead

To learn more about 7-day, Schedule III Butrans, visit www.butrans.com.

WARNING: ADDICTION, ABUSE and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; and NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse Butrans (buprenorphine) exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patientâ&#x20AC;&#x2122;s risk prior to prescribing Butrans, and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.1) and Overdosage (10)]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of Butrans. Monitor for respiratory depression, especially during initiation of Butrans or following a dose increase. Misuse or abuse of Butrans by chewing, swallowing, snorting or injecting

buprenorphine extracted from the transdermal system will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death [see Warnings and Precautions (5.2)]. Accidental Exposure Accidental exposure to even one dose of Butrans, especially by children, can result in a fatal overdose of buprenorphine [see Warnings and Precautions (5.2)]. Neonatal Opioid Withdrawal Syndrome Prolonged use of Butrans during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.3)].

Butrans® (buprenorphine) Transdermal System CIII is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Limitations of Use: Because of the risks of addiction, abuse and misuse with opioids, even at recommended doses, and because of the greater risk of overdose and death with extended-release opioid formulations, reserve Butrans for use in patients for whom alternative treatment options (eg, non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Butrans is not indicated as an as-needed (prn) analgesic. CONTRAINDICATIONS • Butrans is contraindicated in patients with: significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected paralytic ileus; hypersensitivity (eg, anaphylaxis) to buprenorphine.

WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse • B utrans contains buprenorphine, a Schedule III controlled substance. Butrans exposes users to the risks of opioid addiction, abuse, and misuse. As modified-release products such as Butrans deliver the opioid over an extended period of time, there is a greater risk for overdose and death, due to the larger amount of buprenorphine present. Addiction can occur at recommended doses and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Butrans, and monitor all patients during therapy for the development of these behaviors or conditions. Abuse or misuse of Butrans by placing it in the mouth, chewing it, swallowing it, or using it in ways other than indicated may cause choking, overdose and death.

Life-Threatening Respiratory Depression • Serious, life-threatening, or fatal respiratory depression has been reported with modified-release opioids, even when used as recommended, and if not immediately recognized and treated, may lead to respiratory arrest and death. The risk of respiratory depression is greatest during the initiation of therapy or following a dose increase; therefore, closely monitor patients for respiratory depression. Proper dosing and titration of Butrans are essential. Overestimating the Butrans dose when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental exposure to Butrans, especially in children, can result

in respiratory depression and death due to an overdose of buprenorphine.

Neonatal Opioid Withdrawal Syndrome • Prolonged use of Butrans during pregnancy can result in neonatal opioid withdrawal syndrome which may be life-threatening to the neonate if not recognized and treated, and requires management according to protocols developed by neonatology experts.

Interactions with Central Nervous System Depressants • Hypotension, profound sedation, coma, respiratory depression, or death may result if Butrans is used concomitantly with other CNS depressants, including alcohol or illicit drugs that can cause CNS depression. Start with Butrans 5 mcg/ hour patch, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant.

Use in Elderly, Cachectic, and Debilitated Patients and Patients with Chronic Pulmonary Disease • Closely monitor elderly, cachectic, and debilitated patients, and patients with chronic obstructive pulmonary disease because of the increased risk of lifethreatening respiratory depression. Consider the use of alternative nonopioid analgesics in patients with chronic obstructive pulmonary disease if possible.

QTc Prolongation • Avoid in patients with Long QT Syndrome, family history of Long QT Syndrome, or those taking Class IA or Class III antiarrhythmic medications.

Hypotensive Effects • Butrans may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. Monitor patients during dose initiation or titration.

Use in Patients with Head Injury or Increased Intracranial Pressure •M onitor patients taking Butrans who may be susceptible to the intracranial effects

Stamford, CT

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of CO2 retention for signs of sedation and respiratory depression. Avoid the use of Butrans in patients with impaired consciousness or coma.

Application Site Skin Reactions • In rare cases, severe application site skin reactions with signs of marked inflammation including “burn,” “discharge,” and “vesicles” have occurred.

Anaphylactic/Allergic Reactions • C ases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in the post-marketing experience.

Application of External Heat • Avoid exposing the Butrans application site and surrounding area to direct external heat sources. There is a potential for temperature-dependent increases in buprenorphine released from the system resulting in possible overdose and death.

Use in Patients with Gastrointestinal Conditions • Avoid the use of Butrans in patients with paralytic ileus and other GI obstructions. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

ADVERSE REACTIONS • Most common adverse reactions (≥5%) reported by patients treated with Butrans in the clinical trials were nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application site rash.

For more information, visit www.butrans.com.

for transdermal administration BRIEF SUMMARY OF PRESCRIBING INFORMATION (For complete details please see the Full Prescribing Information and Medication Guide.) WARNING: ADDICTION, ABUSE and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; and NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse BUTRANS® exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing BUTRANS, and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.1) and Overdosage (10)]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of BUTRANS. Monitor for respiratory depression, especially during initiation of BUTRANS or following a dose increase. Misuse or abuse of BUTRANS by chewing, swallowing, snorting or injecting buprenorphine extracted from the transdermal system will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death [see Warnings and Precautions (5.2)]. Accidental Exposure Accidental exposure to even one dose of BUTRANS, especially by children, can result in a fatal overdose of buprenorphine [see Warnings and Precautions (5.2)]. Neonatal Opioid Withdrawal Syndrome Prolonged use of BUTRANS during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.3)]. 4 CONTRAINDICATIONS BUTRANS is contraindicated in patients with: • Significant respiratory depression • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment • Known or suspected paralytic ileus • Hypersensitivity (e.g., anaphylaxis) to buprenorphine [see Warnings and Precautions (5.12) and Adverse Reactions (6)] 5 WARNINGS AND PRECAUTIONS 5.1 Addiction, Abuse, and Misuse BUTRANS contains buprenorphine, a Schedule III controlled substance. As an opioid, BUTRANS exposes users to the risks of addiction, abuse, and misuse. As modified-release products such as BUTRANS deliver the opioid over an extended period of time, there is a greater risk for overdose and death, due to the larger amount of buprenorphine present. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed BUTRANS and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused [see Drug Abuse and Dependence (9)]. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing BUTRANS, and monitor all patients receiving BUTRANS for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed modified-release opioid formulations such as BUTRANS, but use in such patients necessitates intensive counseling about the risks and proper use of BUTRANS, along with intensive monitoring for signs of addiction, abuse, or misuse. Abuse or misuse of BUTRANS by placing it in the mouth, chewing it, swallowing it, or using it in ways other than indicated may cause choking, overdose and death [see Overdosage (10)]. Opioid agonists such as BUTRANS are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing BUTRANS. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 5.2 Life-Threatening Respiratory Depression Serious, lifethreatening, or fatal respiratory depression has been reported with the use of modified-release opioids, even when used as recommended. Respiratory depression, from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of BUTRANS, the risk is greatest during the initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with BUTRANS and following dose increases. To reduce the risk of respiratory depression, proper dosing and titration of BUTRANS are essential [see Dosage and Administration (2)]. Overestimating the BUTRANS dose when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental exposure to BUTRANS, especially in children, can result in respiratory depression and death due to an overdose of buprenorphine. 5.3 Neonatal Opioid Withdrawal Syndrome Prolonged use of BUTRANS during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. 5.4 Interactions with Central Nervous System Depressants Hypotension,

profound sedation, coma, respiratory depression, and death may result if BUTRANS is used concomitantly with alcohol or other (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of BUTRANS in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of alcohol or illicit drugs that cause CNS depression. If the decision to begin BUTRANS therapy is made, start with BUTRANS 5 mcg/hour patch, monitor patients for signs of sedation and respiratory depression and consider using a lower dose of the concomitant CNS depressant [see Drug Interactions (7.2)]. 5.5 Use in Elderly, Cachectic, and Debilitated Patients Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Monitor such patients closely, particularly when initiating and titrating BUTRANS and when BUTRANS is given concomitantly with other drugs that depress respiration [see Warnings and Precautions (5.2)]. 5.6 Use in Patients with Chronic Pulmonary Disease Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression for respiratory depression, particularly when initiating therapy and titrating with BUTRANS, as in these patients, even usual therapeutic doses of BUTRANS may decrease respiratory drive to the point of apnea [see Warnings and Precautions (5.2)]. Consider the use of alternative non-opioid analgesics in these patients if possible. 5.7 QTc Prolongation A positive-controlled study of the effects of BUTRANS on the QTc interval in healthy subjects demonstrated no clinically meaningful effect at a BUTRANS dose of 10 mcg/hour; however, a BUTRANS dose of 40 mcg/hour (given as two BUTRANS 20 mcg/hour Transdermal Systems) was observed to prolong the QTc interval [see Dosage and Administration (2.2) and Clinical Pharmacology (12.2)]. Consider these observations in clinical decisions when prescribing BUTRANS to patients with hypokalemia or clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia. Avoid the use of BUTRANS in patients with a history of Long QT Syndrome or an immediate family member with this condition, or those taking Class IA antiarrhythmic medications (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, dofetilide). 5.8 Hypotensive Effects BUTRANS may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions (7.2)]. Monitor these patients for signs of hypotension after initiating or titrating the dose of BUTRANS. 5.9 Use in Patients with Head Injury or Increased Intracranial Pressure Monitor patients taking BUTRANS who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with BUTRANS. BUTRANS may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of BUTRANS in patients with impaired consciousness or coma. 5.10 Hepatotoxicity Although not observed in BUTRANS chronic pain clinical trials, cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving sublingual buprenorphine for the treatment of opioid dependence, both in clinical trials and in post-marketing adverse event reports. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy. In many cases, the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant usage of other potentially hepatotoxic drugs, and ongoing injection drug abuse may have played a causative or contributory role. For patients at increased risk of hepatotoxicity (e.g., patients with a history of excessive alcohol intake, intravenous drug abuse or liver disease), obtain baseline liver enzyme levels and monitor periodically and during treatment with BUTRANS. 5.11 Application Site Skin Reactions In rare cases, severe application site skin reactions with signs of marked inflammation including “burn,” “discharge,” and “vesicles” have occurred. Time of onset varies, ranging from days to months following the initiation of BUTRANS treatment. Instruct patients to promptly report the development of severe application site reactions and discontinue therapy. 5.12 Anaphylactic/Allergic Reactions Cases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in the post-marketing experience. The most common signs and symptoms include rashes, hives, and pruritus. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. A history of hypersensitivity to buprenorphine is a contraindication to the use of BUTRANS. 5.13 Application of External Heat Advise patients and their caregivers to avoid exposing the BUTRANS application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, saunas, hot tubs, and heated water beds while wearing the system because an increase in absorption of buprenorphine may occur [see Clinical Pharmacology (12.3)]. Advise patients against exposure of the BUTRANS application site and surrounding area to hot water or prolonged exposure to direct sunlight. There is a potential for temperature-dependent increases in buprenorphine released from the system resulting in possible overdose and death. 5.14 Patients with Fever Monitor patients wearing BUTRANS systems who develop fever or increased core body temperature due to strenuous exertion for opioid side effects and adjust the BUTRANS dose if signs of respiratory or central nervous system depression occur. 5.15 Use in Patients with Gastrointestinal Conditions BUTRANS is contraindicated in patients with paralytic ileus. Avoid the use of BUTRANS in patients with other GI obstruction. The buprenorphine in BUTRANS may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Opioids may cause increases in the serum amylase. 5.16 Use in Patients with Convulsive or Seizure Disorders The buprenorphine in BUTRANS may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during BUTRANS therapy. 5.17 Driving and Operating Machinery BUTRANS may impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of BUTRANS and know how they will react to the medication. 5.18 Use in Addiction Treatment BUTRANS has not been studied and is not approved for use in the management of addictive disorders. 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling:

• Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] • Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)] • QTc Prolongation [see Warnings and Precautions (5.7)] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3)] • Hypotensive Effects [see Warnings and Precautions (5.8)] • Interactions with Other CNS Depressants [see Warnings and Precautions (5.4)] • Application Site Skin Reactions [see Warnings and Precautions (5.11)] • Anaphylactic/Allergic Reactions [see Warnings and Precautions (5.12)] • Gastrointestinal Effects [see Warnings and Precautions (5.15)] • Seizures [see Warnings and Precautions (5.16)] 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 5,415 patients were treated with BUTRANS in controlled and open-label chronic pain clinical trials. Nine hundred twenty-four subjects were treated for approximately six months and 183 subjects were treated for approximately one year. The clinical trial population consisted of patients with persistent moderate to severe pain. The most common serious adverse drug reactions (all <0.1%) occurring during clinical trials with BUTRANS were: chest pain, abdominal pain, vomiting, dehydration, and hypertension/blood pressure increased. The most common adverse events (≥2%) leading to discontinuation were: nausea, dizziness, vomiting, headache, and somnolence. The most common adverse reactions (≥5%) reported by patients in clinical trials comparing BUTRANS 10 or 20 mcg/hour to placebo are shown in Table 2, and comparing BUTRANS 20 mcg/hour to BUTRANS 5 mcg/hour are shown in Table 3 below: Table 2: Adverse Reactions Reported in ≥5% of Patients during the Open-Label Titration Period and Double-Blind Treatment Period: Opioid-Naïve Patients Open-Label Double-Blind Titration Period Treatment Period BUTRANS BUTRANS Placebo MedDRA (N = 1024) (N = 256) (N = 283) Preferred Term Nausea 23% 13% 10% Dizziness 10% 4% 1% Headache 9% 5% 5% Application site 8% 4% 7% pruritus Somnolence 8% 2% 2% Vomiting 7% 4% 1% Constipation 6% 4% 1% Table 3: Adverse Reactions Reported in ≥5% of Patients during the Open-Label Titration Period and Double-Blind Treatment Period: Opioid-Experienced Patients Open-Label Double-Blind Titration Period Treatment Period BUTRANS BUTRANS 20 BUTRANS 5 MedDRA (N = 1160) (N = 219) (N = 221) Preferred Term Nausea 14% 11% 6% Application site 9% 13% 5% pruritus Headache 9% 8% 3% Somnolence 6% 4% 2% Dizziness 5% 4% 2% Constipation 4% 6% 3% Application site 3% 10% 5% erythema Application 3% 8% 6% site rash Application 2% 6% 2% site irritation The following table lists adverse reactions that were reported in at least 2.0% of patients in four placebo/active-controlled titration-to-effect trials. Table 4: Adverse Reactions Reported in Titration-to-Effect Placebo/ Active-Controlled Clinical Trials with Incidence ≥2% MedDRA Preferred Term BUTRANS (N = 392) Placebo (N = 261) Nausea Application site pruritus Dizziness Headache Somnolence Constipation Vomiting Application site erythema Application site rash Dry mouth Fatigue Hyperhidrosis Peripheral edema Pruritus Stomach discomfort

21% 15% 15% 14% 13% 13% 9% 7% 6% 6% 5% 4% 3% 3% 2%

6% 12% 7% 9% 4% 5% 1% 2% 6% 2% 1% 1% 1% 0% 0%

The adverse reactions seen in controlled and open-label studies are presented below in the following manner: most common (≥5%), common (≥1% to <5%), and less common (<1%). The most common adverse reactions (≥5%) reported by patients treated with BUTRANS in the clinical trials were nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application site rash. The common (≥1% to <5%) adverse reactions reported by patients treated with BUTRANS in the clinical trials organized by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class were: Gastrointestinal disorders: diarrhea, dyspepsia, and upper abdominal pain General disorders and administration site conditions: fatigue, peripheral edema, application

site irritation, pain, pyrexia, chest pain, and asthenia Infections and infestations: urinary tract infection, upper respiratory tract infection, nasopharyngitis, influenza, sinusitis, and bronchitis Injury, poisoning and procedural complications: fall Metabolism and nutrition disorders: anorexia Musculoskeletal and connective tissue disorders: back pain, arthralgia, pain in extremity, muscle spasms, musculoskeletal pain, joint swelling, neck pain, and myalgia Nervous system disorders: hypoesthesia, tremor, migraine, and paresthesia Psychiatric disorders: insomnia, anxiety, and depression Respiratory, thoracic and mediastinal disorders: dyspnea, pharyngolaryngeal pain, and cough Skin and subcutaneous tissue disorders: pruritus, hyperhidrosis, rash, and generalized pruritus Vascular disorders: hypertension Other less common adverse reactions, including those known to occur with opioid treatment, that were seen in <1% of the patients in the BUTRANS trials include the following in alphabetical order: Abdominal distention, abdominal pain, accidental injury, affect lability, agitation, alanine aminotransferase increased, angina pectoris, angioedema, apathy, application site dermatitis, asthma aggravated, bradycardia, chills, confusional state, contact dermatitis, coordination abnormal, dehydration, depersonalization, depressed level of consciousness, depressed mood, disorientation, disturbance in attention, diverticulitis, drug hypersensitivity, drug withdrawal syndrome, dry eye, dry skin, dysarthria, dysgeusia, dysphagia, euphoric mood, face edema, flatulence, flushing, gait disturbance, hallucination, hiccups, hot flush, hyperventilation, hypotension, hypoventilation, ileus, insomnia, libido decreased, loss of consciousness, malaise, memory impairment, mental impairment, mental status changes, miosis, muscle weakness, nervousness, nightmare, orthostatic hypotension, palpitations, psychotic disorder, respiration abnormal, respiratory depression, respiratory distress, respiratory failure, restlessness, rhinitis, sedation, sexual dysfunction, syncope, tachycardia, tinnitus, urinary hesitation, urinary incontinence, urinary retention, urticaria, vasodilatation, vertigo, vision blurred, visual disturbance, weight decreased, and wheezing. 7 DRUG INTERACTIONS 7.1 Benzodiazepines There have been a number of reports regarding coma and death associated with the misuse and abuse of the combination of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection of crushed buprenorphine tablets. Preclinical studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. Closely monitor patients with concurrent use of BUTRANS and benzodiazepines. Warn patients that it is extremely dangerous to self-administer benzodiazepines while taking BUTRANS, and warn patients to use benzodiazepines concurrently with BUTRANS only as directed by their physician. 7.2 CNS Depressants The concomitant use of BUTRANS with other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol can increase the risk of respiratory depression, profound sedation, coma and death. Monitor patients receiving CNS depressants and BUTRANS for signs of respiratory depression, sedation, and hypotension. When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced [see Dosage and Administration (2.2) and Warnings and Precautions (5.4)]. 7.3 Drugs Affecting Cytochrome P450 Isoenzymes Inhibitors of CYP3A4 and 2D6 Because the CYP3A4 isoenzyme plays a major role in the metabolism of buprenorphine, drugs that inhibit CYP3A4 activity may cause decreased clearance of buprenorphine which could lead to an increase in buprenorphine plasma concentrations and result in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of CYP2D6 and 3A4 inhibitors. If co-administration with BUTRANS is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved [see Clinical Pharmacology (12.3)]. Inducers of CYP3A4 CYP450 3A4 inducers may induce the metabolism of buprenorphine and, therefore, may cause increased clearance of the drug which could lead to a decrease in buprenorphine plasma concentrations, lack of efficacy or, possibly, development of an abstinence syndrome in a patient who had developed physical dependence to buprenorphine. After stopping the treatment of a CYP3A4 inducer, as the effects of the inducer decline, the buprenorphine plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression. If co-administration or discontinuation of a CYP3A4 inducer with BUTRANS is necessary, monitor for signs of opioid withdrawal and consider dose adjustments until stable drug effects are achieved [see Clinical Pharmacology (12.3)]. 7.4 Muscle Relaxants Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Monitor patients receiving muscle relaxants and BUTRANS for signs of respiratory depression that may be greater than otherwise expected. 7.5 Anticholinergics Anticholinergics or other drugs with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when BUTRANS is used concurrently with anticholinergic drugs. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Clinical Considerations Fetal/neonatal adverse reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Observe newborns for symptoms of neonatal opioid withdrawal syndrome, such as poor feeding, diarrhea, irritability, tremor, rigidity, and seizures, and manage accordingly [see Warnings and Precautions (5.3)]. Teratogenic Effects - Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. BUTRANS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In animal studies, buprenorphine caused an increase in the number of stillborn offspring, reduced litter size, and reduced offspring growth in rats at maternal exposure levels that were approximately 10 times that of human subjects who received one BUTRANS 20 mcg/hour, the maximum recommended human dose (MRHD). Studies in rats and rabbits demonstrated no evidence of teratogenicity following BUTRANS or subcutaneous (SC) administration of buprenorphine during the period of major organogenesis. Rats were administered up to one BUTRANS 20 mcg/hour every 3 days (gestation days 6, 9, 12, & 15) or received daily SC buprenorphine up to 5 mg/kg (gestation days 6-17). Rabbits were administered four BUTRANS 20 mcg/hour every 3 days (gestation days 6, 9, 12, 15, 18, & 19) or received daily SC buprenorphine up to 5 mg/kg (gestation days 6-19). No teratogenicity was observed at any dose. AUC values for buprenorphine with BUTRANS application and SC injection were approximately 110 and 140 times, respectively, that of human subjects who received the MRHD of one BUTRANS 20 mcg/hour. Non-Teratogenic Effects In a peri- and post-natal study conducted in pregnant and lactating rats, administration of buprenorphine either as BUTRANS or SC buprenorphine was associated with toxicity to offspring. Buprenorphine was present in maternal milk. Pregnant

rats were administered 1/4 of one BUTRANS 5 mcg/hour every 3 days or received daily SC buprenorphine at doses of 0.05, 0.5, or 5 mg/kg from gestation day 6 to lactation day 21 (weaning). Administration of BUTRANS or SC buprenorphine at 0.5 or 5 mg/kg caused maternal toxicity and an increase in the number of stillborns, reduced litter size, and reduced offspring growth at maternal exposure levels that were approximately 10 times that of human subjects who received the MRHD of one BUTRANS 20 mcg/hour. Maternal toxicity was also observed at the no observed adverse effect level (NOAEL) for offspring. 8.2 Labor and Delivery Opioids cross the placenta and may produce respiratory depression in neonates. BUTRANS is not for use in women during and immediately prior to labor, when shorter acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. 8.3 Nursing Mothers Buprenorphine is excreted in breast milk. The amount of buprenorphine received by the infant varies depending on the maternal plasma concentration, the amount of milk ingested by the infant, and the extent of first pass metabolism. Withdrawal symptoms can occur in breast-feeding infants when maternal administration of buprenorphine is stopped. Because of the potential for adverse reactions in nursing infants from BUTRANS, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use The safety and efficacy of BUTRANS in patients under 18 years of age has not been established. 8.5 Geriatric Use Of the total number of subjects in the clinical trials (5,415), BUTRANS was administered to 1,377 patients aged 65 years and older. Of those, 457 patients were 75 years of age and older. In the clinical program, the incidences of selected BUTRANS-related AEs were higher in older subjects. The incidences of application site AEs were slightly higher among subjects <65 years of age than those ≥65 years of age for both BUTRANS and placebo treatment groups. In a single-dose study of healthy elderly and healthy young subjects treated with BUTRANS 10 mcg/hour, the pharmacokinetics were similar. In a separate dose-escalation safety study, the pharmacokinetics in the healthy elderly and hypertensive elderly subjects taking thiazide diuretics were similar to those in the healthy young adults. In the elderly groups evaluated, adverse event rates were similar to or lower than rates in healthy young adult subjects, except for constipation and urinary retention, which were more common in the elderly. Although specific dose adjustments on the basis of advanced age are not required for pharmacokinetic reasons, use caution in the elderly population to ensure safe use [see Clinical Pharmacology (12.3)]. 8.6 Hepatic Impairment In a study utilizing intravenous buprenorphine, peak plasma levels (Cmax) and exposure (AUC) of buprenorphine in patients with mild and moderate hepatic impairment did not increase as compared to those observed in subjects with normal hepatic function. BUTRANS has not been evaluated in patients with severe hepatic impairment. As BUTRANS is intended for 7-day dosing, consider the use of alternate analgesic therapy in patients with severe hepatic impairment [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)]. 9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance BUTRANS contains buprenorphine, a Schedule III controlled substance with an abuse potential similar to other Schedule III opioids. BUTRANS can be abused and is subject to misuse, addiction and criminal diversion [see Warnings and Precautions (5.1)]. 9.2 Abuse All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited to the following examples: the use of a prescription or over-the-counter drug to get “high”, or the use of steroids for performance enhancement and muscle build up. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “Drug-seeking” behavior is very common to addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated claims of loss of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction. BUTRANS, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful recordkeeping of prescribing information, including quantity, frequency, and renewal requests, as required by state law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to reduce abuse of opioid drugs. Risks Specific to the Abuse of BUTRANS BUTRANS is intended for transdermal use only. Abuse of BUTRANS poses a risk of overdose and death. This risk is increased with concurrent abuse of BUTRANS with alcohol and other substances including other opioids and benzodiazepines [see Warnings and Precautions (5.4) and Drug Interactions (7.2)]. Intentional compromise of the transdermal delivery system will result in the uncontrolled delivery of buprenorphine and pose a significant risk to the abuser that could result in overdose and death [see Warnings and Precautions (5.1)]. Abuse may occur by applying the transdermal system in the absence of legitimate purpose, or by swallowing, snorting, or injecting buprenorphine extracted from the transdermal system. 9.3 Dependence Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, or mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. BUTRANS should not be abruptly discontinued [see Dosage and Administration (2.3)]. If BUTRANS is abruptly discontinued in a physicallydependent patient, an abstinence syndrome may occur. Some or all of the

following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms [see Use in Specific Populations (8.1)]. 10 OVERDOSAGE Clinical Presentation Acute overdosage with BUTRANS is manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations. Treatment of Overdose In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques. Naloxone may not be effective in reversing any respiratory depression produced by buprenorphine. High doses of naloxone, 10-35 mg/70 kg, may be of limited value in the management of buprenorphine overdose. The onset of naloxone effect may be delayed by 30 minutes or more. Doxapram hydrochloride (a respiratory stimulant) has also been used. Remove BUTRANS immediately. Because the duration of reversal would be expected to be less than the duration of action of buprenorphine from BUTRANS, carefully monitor the patient until spontaneous respiration is reliably re-established. Even in the face of improvement, continued medical monitoring is required because of the possibility of extended effects as buprenorphine continues to be absorbed from the skin. After removal of BUTRANS, the mean buprenorphine concentrations decrease approximately 50% in 12 hours (range 10-24 hours) with an apparent terminal half-life of approximately 26 hours. Due to this long apparent terminal half-life, patients may require monitoring and treatment for at least 24 hours. In an individual physically dependent on opioids, administration of an opioid receptor antagonist may precipitate an acute withdrawal. The severity of the withdrawal produced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient with an opioid antagonist, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist. 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Addiction, Abuse, and Misuse Inform patients that the use of BUTRANS, even when taken as recommended, can result in addiction, abuse, and misuse, which could lead to overdose and death [see Warnings and Precautions (5.1)]. Instruct patients not to share BUTRANS with others and to take steps to protect BUTRANS from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting BUTRANS or when the dose is increased, and that it can occur even at recommended doses [see Warnings and Precautions (5.2)]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop. Accidental Exposure Inform patients that accidental exposure, especially in children, may result in respiratory depression or death [see Warnings and Precautions (5.2)]. Instruct patients to take steps to store BUTRANS securely and to dispose of unused BUTRANS by folding the patch in half and flushing it down the toilet. Neonatal Opioid Withdrawal Syndrome Inform female patients of reproductive potential that prolonged use of BUTRANS during pregnancy can result in neonatal opioid withdrawal syndrome, which may be lifethreatening if not recognized and treated [see Warnings and Precautions (5.3)]. Interaction with Alcohol and other CNS Depressants Inform patients that potentially serious additive effects may occur if BUTRANS is used with alcohol or other CNS depressants, and not to use such drugs unless supervised by a health care provider. Important Administration Instructions Instruct patients how to properly use BUTRANS, including the following: 1. To carefully follow instructions for the application, removal, and disposal of BUTRANS. Each week, apply BUTRANS to a different site based on the 8 described skin sites, with a minimum of 3 weeks between applications to a previously used site. 2. To apply BUTRANS to a hairless or nearly hairless skin site. If none are available, instruct patients to clip the hair at the site and not to shave the area. Instruct patients not to apply to irritated skin. If the application site must be cleaned, use clear water only. Soaps, alcohol, oils, lotions, or abrasive devices should not be used. Allow the skin to dry before applying BUTRANS. Hypotension Inform patients that BUTRANS may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position). Driving or Operating Heavy Machinery Inform patients that BUTRANS may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication. Constipation Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention. Anaphylaxis Inform patients that anaphylaxis has been reported with ingredients contained in BUTRANS. Advise patients how to recognize such a reaction and when to seek medical attention. Pregnancy Advise female patients that BUTRANS can cause fetal harm and to inform the prescriber if they are pregnant or plan to become pregnant. Disposal Instruct patients to refer to the Instructions for Use for proper disposal of BUTRANS. Patients can dispose of used or unused BUTRANS patches in the trash by sealing them in the Patch-Disposal Unit, following the instructions on the unit. Alternatively, instruct patients to dispose of used patches by folding the adhesive side of the patch to itself, then flushing the patch down the toilet immediately upon removal. Unused patches should be removed from their pouches, the protective liners removed, the patches folded so that the adhesive side of the patch adheres to itself, and immediately flushed down the toilet. Instruct patients to dispose of any patches remaining from a prescription as soon as they are no longer needed. Healthcare professionals can telephone Purdue Pharma’s Medical Services Department (1-888-726-7535) for information on this product. Distributed by: Purdue Pharma L.P., Stamford, CT 06901-3431 Manufactured by: LTS Lohmann Therapy Systems Corp., West Caldwell, NJ 07006 U.S. Patent Numbers 5681413; 5804215; 6264980; 6315854; 6344211; RE41408; RE41489; RE41571. © 2014, Purdue Pharma L.P. This brief summary is based on BUTRANS Prescribing Information 303385-0A, Revised 06/2014 (A)

Trust, But Verify: Essentials of Urine Drug Testing in Pain Medicine By Gary M. Reisfield, MD, and Roger L. Bertholf, PhD

he single most important element of medical diagnosis and treatment is the patient history, so we must listen carefully to and believe what our patients tell us. On the other hand, when caring for patients with (often unrecognized) substance use disorders—with prescriptions for opioids, benzodiazepines, and stimulants hanging in the balance—we must be alert to the reality that our patients may sometimes provide us with less than truthful information about what they are taking and how they are doing. Between 2000 and 2014 there were approximately 180,000 prescription opioid-involved deaths in the United States (1), a large proportion of which involved benzodiazepines and other central nervous system depressants. For every one prescription painkiller death, there are approximately 10 treatment admissions for prescription opioid abuse, 32 emergency room visits related to prescription opioid abuse, 130 people who have prescription opioid use disorders, and 825 people who use prescription opioids nonmedically (2). Studies have revealed a high incidence of abnormal, or unexpected, results of random urine toxicology screens among patients prescribed opioids for chronic pain. For example, in one well-designed study performed at a Harvardaffiliated pain management program, urine samples from 470 patients on long-term opioid therapy showed that only 55% of the patients had expected drug test results (3). How, then, do we manage this tension between wanting and needing to believe our patients, and knowing that they’re sometimes not completely truthful with us? As Ronald Reagan was fond of saying to Mikhail Gorbachev during the Cold War nuclear arms negotiations, “Trust, but verify.” Verifying that our patients are staying safe includes speaking with them (and sometimes their loved ones) about how they are doing in their lives, being alert for potentially aberrant behaviors, checking state prescription monitoring database, and performing drug testing. The recently released CDC Guideline for Prescribing Opioids for Chronic Pain recommends performing urine drug testing before beginning

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opioid therapy and at least annually thereafter to assess for the presence of prescribed medications and the absence of non-prescribed controlled substances and illicit drugs (4). Types of Drug Testing

Screening tests Drug testing usually begins with a screening test, typically an immunoassay-based technique, which may be performed at the point-of-care or in the laboratory. Most commonly, point of care testing involves non-automated techniques, e.g., urine specimen cups with integrated test strips, while laboratory testing ordinarily comprises more complex, fully automated techniques. The Clinical Laboratory Improvement Amendments of 1988 (CLIA 88) classifies tests according to their complexity. Point-of-care test devices that meet specific complexity, error, and risk requirements may be classified as waived, meaning they are subject to minimal federal regulation. These waived tests are required to be simple and to pose low risk for error, but in reality, their reliability is highly dependent upon office personnel being familiar with the tests and assiduously following the manufacturer’s instructions. For moderate- and high-complexity laboratory-based tests, personnel must meet certain educational requirements, and the labs are subject to quality assurance and quality control stipulations, proficiency testing, and inspections. These measures increase the uniformity and reliability of results from laboratory-based immunoassays compared to point-of-care immunoassays. Moreover, clinical and toxicology laboratories typically have the capacity to analyze a wider selection of analytes. The turnaround time for laboratory results, however, is measured in hours to days, while point-of-care test results are available within minutes. Turnaround time is an important consideration because it means, in the case of point-of-care testing, that the clinician can sit down with the patient at the time of the test and have a face-to-face discussion about the meaning of the result while the history of very recent prescription or other drug

TRUST, BUT VERIF Y: ESSENTIALS OF URINE DRUG TESTING IN PAIN MEDICINE

Urine samples from 470 patients on long-term opioid therapy showed that only 55% of the patients had expected drug test results.

SHUTTERSTOCK: DOCTER_K

use is fresh in the patient’s mind. With lab-based testing, the clinician loses that option. They’re both inexpensive and accurate enough for screening purposes, but for some clinicians, point-of-care testing offers a distinct advantage with regard to contemporaneous result management Limitations of screening tests Immunoassays, whether performed at the point-of-care or in the laboratory, have three important limitations. First, there is a limit to the number and types of drugs that can be detected. It is sometimes assumed that a drug screen is a general screen for a large array of drugs, but this is not true. Every product and laboratory has a limited test menu, sometimes comprising assays for a very small number of drugs, so the clinician should be acquainted with the menu of analytes offered. Second, there are specificity limitations because, in the case of amphetamines, barbiturates, benzodiazepines, and opiates, the tests are class-specific rather than drug-specific.

In some settings, this lack of drug specificity is not a problem—indeed, it may be an advantage—because it provides the potential for a single assay to detect several drugs within a class. This is useful in the emergency room, for example, where therapy for a suspected overdose is contingent upon rapidly identifying the class of drug, rather than a specific member of the class. For example, flumazenil is an effective antidote to benzodiazepine toxicity, and may be administered in response to an overdose of any of the many benzodiazepines used therapeutically; it would not be necessary to identify the specific drug. Within-class cross-reactivity can be a disadvantage, however, when more specific information is needed. In the pain clinic, for example, it is a limitation that opiate immunoassays are incapable of distinguishing between the hydrocodone that a clinician is prescribing and the heroin that a patient is surreptitiously abusing. Opiate screening immunoassays are based on antibody-antigen reactions, and the antibodies are usually raised against morphine. Codeine has a molecular THE PAIN PRACTITIONE R

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structure very similar to morphine, as do some of the semisynthetic opiates such as hydrocodone and hydromorphone, which share the basic morphine chemical backbone. As a consequence, the opiate immunoassays are cross-reactive with codeine, hydrocodone, hydromorphone, and certain other semisynthetic opiates, although few of the opiate screening methods detect oxycodone and oxymorphone. Another type of cross-reactivity may occur between unrelated molecules. Levofloxacin, for example, sometimes causes false-positive opiate results because, although structurally dissimilar from the opiate, the antibiotic, in three dimensional space, displays an antigenic determinant similar to that of morphine (5). There potentially are innumerable examples of this type of cross-reactivity, only some of which have been discovered and reported. The final limitation of drug screening methods is sensitivity. Sensitivity is determined administratively as a cutoff concentration. Analyte concentrations above the cutoff are reported as presumptive positive; concentrations below the cutoff are reported as presumptive negative. Thus, these tests

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Figure 1.

are incapable of verifying the absence of an analyte of interest; a negative means that an analyte may be absent or may be present at a concentration below the administratively determined cutoff value. With regard to test sensitivity, there are two additional points to consider. First, for the class-specific assays, the antibodies are raised against a specific member of the drug class. In the previously cited example of opiates, the antibodies are typically raised against morphine. Thus, the opiate immunoassay, which is calibrated to detect morphine when it reaches a threshold concentration, may be more or less sensitive to other opiates at that same concentration, depending on the affinity of the antibody toward congeneric drugs. Put another way, it may require higher concentrations of some opiates to yield a positive test result, while other opiates may produce a positive result at lower than the threshold concentration. Small differences in the chemical structures of the molecules change their three-dimensional conformation and thus change the way they react with anti-morphine antibodies. For example, hydromorphone differs from morphine at the C7-8 position, where morphine’s double bond has been reduced, and at the C6 position, where the hydroxyl group has been oxidized to a ketone group. In the case of oxycodone, both of those changes occur, but with the additions of a methyl group to the oxygen on C3 and a hydroxyl group at the C9 position. As a result, while the clinical opiate immunoassay is typically calibrated to detect morphine at 300 ng/mL, on one

TRUST, BUT VERIF Y: ESSENTIALS OF URINE DRUG TESTING IN PAIN MEDICINE

Definitive drug tests in clinical settings nearly always involve chromatography paired with mass spectrometry. widely available point-of-care device, hydromorphone must be present at a concentration an order of magnitude higher—3,000 ng/mL or more—to yield a positive test result. In the case of oxycodone, its concentration must be two orders of magnitude higher, or 30,000 ng/mL, to yield a positive result, making it practically useless for detecting the drug at common clinical dosages. For this reason many tests include separate assays for opiates and oxycodone. (Figure 1.) Second, if immunoassay-based screens are designed to detect parent drugs, they may be poorly reactive with metabolites (and vice versa). For example, a methadone test may be calibrated to yield a positive result at 300 ng/mL of methadone, but may require 50,000 ng/mL of methadone’s primary metabolite, EDDP, to yield a positive result. Thus, a

patient who is also taking a drug that is an inducer of cytochrome P450 3A—and hence is a rapid metabolizer—may excrete relatively low urine concentrations of methadone and a relatively high concentrations of EDDP, possibly yielding a “clinical false negative” drug screen result. Definitive Tests

Definitive (sometimes called “confirmatory”) drug tests in clinical settings nearly always involve chromatography paired with mass spectrometry; currently, the most commonly used technique is liquid chromatography paired with tandem mass spectrometry (LC-MS/MS). Liquid chromatography separates the analytes in the urine based on their differential affinities with the mobile and stationary phases of a chromatographic column. As an analyte of interest elutes from the column according to its characteristic retention time, the mass spectrometer ionizes the analyte, with subsequent analysis of fragment (product) ions on the basis of their mass-to-charge ratios. This technology has the capability to identify analytes with very high analytical sensitivity and specificity and, if appropriately calibrated,

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can provide quantitative results. When to use definitive testing We have developed an algorithm for determining which screening results are sent to the laboratory for highly sensitive and specific, but more expensive, definitive testing. 1. If the screening result is presumptively positive for an analyte that should be absent from the urine or is presumptively negative for an analyte that should be present in the urine and the patient’s account of their drug use is at variance with the test result, definitive testing is required. Given the inherent performance limitations of immunoassay-based screening tests, deference should be given to the patient’s account until proven otherwise by definitive testing. 2. If testing is required for a drug or metabolite for which we have no screening test available—alcohol metabolites, synthetic cannabinoids, cathinones, and ketamine, for example—we will request specific testing by LC-MS/MS for the analyte of interest. 3. If we need a degree of specificity not afforded by a class-specific assay—to determine the specific opioid(s), benzodiazepine(s), or barbiturate(s) responsible for a pre-

sumptive positive result—we will request specific drug and/or metabolite identification from LC-MS/MS. 4. If quantification of an analyte is necessary—typically for monitoring the cessation of unauthorized use of lipid soluble drugs (e.g. cannabis, diazepam) that may continue to appear in urine for weeks (or longer) after last use—we will follow (generally) decreasing serial creatinine- or specific gravity-adjusted concentrations of drug metabolites to verify abstinence. 5. If we have reasonable suspicion that a patient has “spiked” a urine specimen with a prescribed drug that he or she has been abusing, stockpiling, or diverting, a presumptive positive screening result will not address our concern. Definitive testing will be able to identify and quantitate metabolites, confirming or disconfirming drug administration. 6. Finally, in the occasional instances in which the screening result is presumptive negative, but the pre-test probability of drug use is high (e.g., the patient with a history of cocaine use disorder and suspected recent cocaine use), we will request definitive testing for the drug or metabolite of interest if the LC-MS/MS method offers greater sensitivity (i.e., lower limit of detection) than the screening assay. References 1. 2.

3. 4. 5.

CDC/NCHS, National Vital Statistics System, Mortality File. Available at: https://www.cdc.gov/nchs/data/health_policy/AADR_drug_poisoning_ involving_OA_Heroin_US_2000-2014.pdf. Accessed August 11, 2016. Policy impact: prescription painkiller overdoses. Centers for Disease Control and Prevention. National Center for Injury Prevention and Control, Division of Unintentional Injury Prevention. Available at: http://www.cdc.gov/drugoverdose/pdf/policyimpact-prescriptionpainkillerod-a.pdf. Accessed August 11, 2016. Michna E, Jamison RN, Pham LD, et al. Urine toxicology screening among chronic pain patients on opioid therapy: frequency and predictability of abnormal findings. Clin J Pain. 2007;23(2):173-179. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain – United States, 2016. MMWE Recomm Rep 2016;65:1-49 Baden LR, Horowitz G, Jacoby H, Eliopoulos GM. Quinolones and falsepositive urine screening for opiates by immunoassay technology. JAMA. 2001;286(24):3115-3119.

Gary M. Reisfield, MD, is clinical associate professor, department of psychiatry, Divisions of Addiction Medicine and Forensic Psychiatry, University of Florida Health, Gainesville, Florida. Roger L. Bertholf, PhD, is professor, department of pathology and laboratory medicine, and Director of Clinical Chemistry, Toxicology, and Point-of-Care Testing, University of Florida Health, Jacksonville, Florida.

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To learn more, visit XtampzaER.com INDICATIONS AND USAGE Xtampza™ ER (oxycodone) is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Limitations of Use • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve Xtampza ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufﬁcient management of pain • Xtampza ER is not indicated as an as-needed (prn) analgesic IMPORTANT SAFETY INFORMATION WARNING: ADDICTION, ABUSE, and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and CYTOCHROME P450 3A4 INTERACTION Addiction, Abuse, and Misuse Xtampza ER exposes patients and other users to the risks of opioid addiction, abuse and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing Xtampza ER and monitor all patients regularly for the development of these behaviors or conditions. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of Xtampza ER. Monitor for respiratory depression, especially during initiation of Xtampza ER or following a dose increase. Accidental Ingestion Accidental ingestion of even one dose of Xtampza ER, especially by children, can result in a fatal overdose of oxycodone. Neonatal Opioid Withdrawal Syndrome Prolonged use of Xtampza ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Cytochrome P450 3A4 Interaction The concomitant use of Xtampza ER with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving Xtampza ER and any CYP3A4 inhibitor or inducer. Please see additional Important Safety Information and accompanying brief summary of the full Prescribing Information. Xtampza ER is a trademark of Collegium Pharmaceutical, Inc. ©2016 Collegium Pharmaceutical, Inc. All rights reserved. PP-XT-US-0085

XTAMPZA ER (oxycodone) extended-release capsules, for oral use, CII BRIEF SUMMARY OF PRESCRIBING INFORMATION (For complete details please see Full Prescribing Information and Medication Guide at XtampzaER.com.) WARNING: ADDICTION, ABUSE, and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and CYTOCHROME P450 3A4 INTERACTION Addiction, Abuse, and Misuse XTAMPZA ER exposes patients and other users to the risks of opioid addiction, abuse and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing XTAMPZA ER and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.1)]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of XTAMPZA ER. Monitor for respiratory depression, especially during initiation of XTAMPZA ER or following a dose increase [see Warnings and Precautions (5.2)]. Accidental Ingestion Accidental ingestion of even one dose of XTAMPZA ER, especially by children, can result in a fatal overdose of oxycodone [see Warnings and Precautions (5.2)]. Neonatal Opioid Withdrawal Syndrome Prolonged use of XTAMPZA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.3)]. Cytochrome P450 3A4 Interaction The concomitant use of XTAMPZA ER with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving XTAMPZA ER and any CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.4) and Clinical Pharmacology (12.3)]. 4 CONTRAINDICATIONS XTAMPZA ER is contraindicated in patients with: - Significant respiratory depression [see Warnings and Precautions (5.2)] - Acute or severe bronchial asthma is an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.6)] - Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.10)] - Hypersensitivity (e.g., anaphylaxis) to oxycodone 5 WARNINGS AND PRECAUTIONS 5.1 Addiction, Abuse, and Misuse XTAMPZA ER contains oxycodone, a Schedule II controlled substance. As an opioid, XTAMPZA ER exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)]. As extended-release products such as XTAMPZA ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of oxycodone present [see Drug Abuse and Dependence (9)]. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed XTAMPZA ER. Addiction can occur at recommended dosages and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing XTAMPZA ER, and monitor all patients receiving XTAMPZA ER for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as XTAMPZA ER, but use in such patients necessitates intensive counseling about the risks and proper use of XTAMPZA ER along with intensive monitoring for signs of addiction, abuse, and misuse. Abuse or misuse of XTAMPZA ER by snorting or by injecting the dissolved product can result in overdose and death [see Overdosage (10)]. Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing XTAMPZA ER. Strategies to reduce these risks include prescribing the drug in the smallest

appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 5.2 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of XTAMPZA ER, the risk is greatest during the initiation of therapy or following a dosage increase. Closely monitor patients for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of XTAMPZA ER. To reduce the risk of respiratory depression, proper dosing and titration of XTAMPZA ER are essential [see Dosage and Administration (2)]. Overestimating the XTAMPZA ER dose when converting patients from another opioid product can result in a fatal overdose with the first dose. Accidental ingestion of even one dose of XTAMPZA ER, especially by children, can result in respiratory depression and death due to an overdose of oxycodone. 5.3 Neonatal Opioid Withdrawal Syndrome Prolonged use of XTAMPZA ER during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. [see Use in Specific Populations (8.1), Patient Counseling Information (17)]. 5.4 Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers Concomitant use of XTAMPZA ER with a CYP3A4 inhibitor, such as antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see Warnings and Precautions (5.2)], particularly when an inhibitor is added after a stable dose of XTAMPZA ER is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in XTAMPZA ERtreated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions. When using XTAMPZA ER with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in XTAMPZA ER-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of XTAMPZA ER until stable drug effects are achieved [see Drug Interactions (7)]. Concomitant use of XTAMPZA ER with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone. When using XTAMPZA ER with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see Drug Interactions (7)]. 5.5 Risks Due to Interactions with Central Nervous System Depressants Hypotension, profound sedation, respiratory depression, coma, and death may result if XTAMPZA ER is used concomitantly with other central nervous system (CNS) depressants (e.g., benzodiazepines and other sedative-hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids). When considering the use of XTAMPZA ER in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of alcohol or illicit drugs that can cause CNS depression. If the decision to begin XTAMPZA ER therapy is made, start with 1/3 to 1/2 the usual dose XTAMPZA ER, monitor patients for signs of respiratory depression, sedation, and hypotension, and consider using a lower dose of the concomitant CNS depressant. Use an alternative analgesic for patients who require a dose of XTAMPZA ER less than 9 mg [see Drug Interactions (7)]. 5.6 Risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of XTAMPZA ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: XTAMPZA ER-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of XTAMPZA ER [see Warnings and Precautions (5.2)]. Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Monitor such patients closely, particularly when initiating and titrating XTAMPZA ER and when XTAMPZA ER is given concomitantly with other drugs that depress respiration [see Warnings and Precautions (5.2)]. Alternatively, consider the use of non-opioid analgesics in these patients. Use an alternative analgesic for patients who require a dose of XTAMPZA ER less than 9 mg. 5.7 Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. 5.8 Severe Hypotension XTAMPZA ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions (7)]. Monitor these patients for signs of hypotension after initiating or titrating the dosage of XTAMPZA ER. In patients with circulatory shock, XTAMPZA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of XTAMPZA ER in patients with circulatory shock. 5.9 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), XTAMPZA ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with XTAMPZA ER. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of XTAMPZA ER in patients with impaired consciousness or coma. 5.10 Risks of Use in Patients with Gastrointestinal Conditions XTAMPZA ER is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus. The oxycodone in XTAMPZA ER may cause spasm of the sphincter of Oddi. Opioids may cause increases in the serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. 5.11 Risk of Use in Patients with Seizure Disorders The oxycodone in XTAMPZA ER may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during XTAMPZA ER therapy. 5.12 Withdrawal Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including XTAMPZA ER. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms. When discontinuing XTAMPZA ER, gradually taper the dosage [see Dosage and Administration (2.5)]. Do not abruptly discontinue XTAMPZA ER. 5.13 Risks of Driving and Operating Machinery XTAMPZA ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of XTAMPZA ER and know how they will react to the medication.

5.14 Laboratory Monitoring Not every urine drug test for “opioids” or “opiates” detects oxycodone reliably, especially those designed for in-office use. Further, many laboratories will report urine drug concentrations below a specified “cut-off” value as “negative”. Therefore, if urine testing for oxycodone is considered in the clinical management of an individual patient, ensure that the sensitivity and specificity of the assay is appropriate, and consider the limitations of the testing used when interpreting results. 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: - Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] - Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)] - Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3)] - Interactions with Other CNS Depressants [see Warnings and Precautions (5.5)] - Adrenal Insufficiency [see Warnings and Precautions (5.7)] - Severe Hypotension [see Warnings and Precautions (5.8)] - Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.10)] - Seizures [see Warnings and Precautions (5.11)] - Withdrawal [see Warnings and Precautions (5.12)] 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of XTAMPZA ER was evaluated in a Phase 3, randomized withdrawal, double-blind clinical trial involving 740 patients with moderate-to-severe chronic lower back pain. In the doubleblind maintenance phase, 389 patients were randomized and 193 patients were assigned to the XTAMPZA ER treatment group. The most common AEs (>5%) reported by patients in the Phase 3 clinical trial during the titration phase were: nausea (16.6%), headache (13.9%), constipation (13.0%), somnolence (8.8%), pruritus (7.4%), vomiting (6.4%), and dizziness (5.7%). The most common adverse reactions (>5%) reported by patients in the Phase 3 clinical trial comparing XTAMPZA ER with placebo are shown in Table 1 below: Table 1: Common Adverse Reactions (>5%) Adverse Reaction Nausea Headache Constipation Somnolence Pruritus Vomiting Dizziness

Titration XTAMPZA ER (n = 740) % 16.6 13.9

13.0 8.8 7.4 6.4 5.7

Maintenance XTAMPZA ER Placebo (n = 193) % (n = 196) % 10.9 4.6 6.2 11.7 5.2 0.5 <1 <1

2.6 4.1 1.6

1.5 1.5 0

In the Phase 3 clinical trial, the following adverse reactions were reported in patients treated with XTAMPZA ER with incidences of 1% to 5%: Eye disorders: vision blurred Gastrointestinal disorders: abdominal pain, upper abdominal pain, diarrhea, gastroesophageal reflux disease General disorders and administration site conditions: chills, drug withdrawal syndrome, fatigue, irritability, edema, pyrexia Injury, poisoning and procedural complications: excoriation Metabolism and nutrition disorders: decreased appetite, hyperglycemia Musculoskeletal and connective tissue disorders: arthralgia, back pain, musculoskeletal pain, myalgia Nervous system disorders: migraine, tremor Psychiatric disorders: anxiety, insomnia, withdrawal syndrome Respiratory, thoracic and mediastinal disorders: cough, oropharyngeal pain Skin and subcutaneous tissue disorders: hyperhidrosis, rash Vascular disorders: hot flush, hypertension In the Phase 3 clinical trial, the following treatment-related adverse reactions were reported in patients treated with XTAMPZA ER with incidences of less than 1% of patients. Investigations: increased gamma-glutamyl transferase, increased heart rate Nervous system disorders: lethargy, memory impairment, poor-quality sleep Psychiatric disorders: abnormal dreams, euphoric mood, restlessness Respiratory, thoracic and mediastinal disorders: dyspnea Skin and subcutaneous tissue disorders: night sweats

6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of oxycodone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis: Anaphylaxis has been reported with ingredients contained in XTAMPZA ER. Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology (12.2)]. 7 DRUG INTERACTIONS Table 2 includes clinically significant drug interactions with XTAMPZA ER. Table 2: Clinically Significant Drug Interactions with XTAMPZA ER. Inhibitors of CYP3A4 and CYP2D6 Clinical Impact: The concomitant use of XTAMPZA ER and CYP3A4 inhibitors can increase the plasma concentration of oxycodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of XTAMPZA ER and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of XTAMPZA ER is achieved [see Warnings and Precautions (5.4)]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oxycodone plasma concentration will decrease [see Clinical Pharmacology (12.3)], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to oxycodone. Intervention: If concomitant use is necessary, consider dosage reduction of XTAMPZA ER until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the XTAMPZA ER dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of XTAMPZA ER and CYP3A4 inducers can decrease the plasma concentration of oxycodone [see Clinical Pharmacology (12.3)], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oxycodone [see Warnings and Precautions (5.4)]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the oxycodone plasma concentration will increase [see Clinical Pharmacology (12.3)], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the XTAMPZA ER dosage until stable drug effects are achieved [see Dosage and Administration (2.4)]. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider XTAMPZA ER dosage reduction and monitor for signs of respiratory depression. Examples: Rifampin, carbamazepine, phenytoin Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacological effects, the concomitant use of CNS depressants can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.

Intervention:

Examples:

Consider dose reduction of one or both drugs. Monitor patients for signs of respiratory depression, sedation, and hypotension [see Warnings and Precautions (5.5)]. Alcohol, benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids.

Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue XTAMPZA ER if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of XTAMPZA ER and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: Butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Oxycodone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of XTAMPZA ER and/or the muscle relaxant as necessary. Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when XTAMPZA ER is used concomitantly with anticholinergic drugs.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.3)]. There are no available data with XTAMPZA ER in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, there was no embryo-fetal toxicity when oxycodone hydrochloride was orally administered to rats and rabbits, during the period of organogenesis, at doses 0.5 to 15 times the adult human dose of 160 mg/day, respectively. In a pre- and postnatal toxicity study, when oxycodone was orally administered to rats, there was transiently decreased pup body weight during lactation and the early post-weaning period at the dose equivalent to approximately 0.4-times an adult dose of 160 mg/day. In several published studies, treatment of pregnant rats with oxycodone hydrochloride at clinically relevant doses and below resulted in neurobehavioral effects in offspring [see Data]. Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations Fetal/neonatal adverse reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration of use, and severity of neonatal opioid withdrawal syndrome may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.3)]. Labor or delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in the neonate. XTAMPZA ER is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including XTAMPZA ER, can prolong labor through actions which temporarily reduce the strength, duration and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. 8.2 Lactation Risk Summary Oxycodone is present in breast milk. Published lactation studies report variable concentrations of oxycodone in breast milk with administration of immediate-release oxycodone to nursing mothers in the early postpartum period. The lactation studies did not assess breastfed infants for potential adverse reactions. Lactation studies have not been conducted with extended-release oxycodone, including XTAMPZA ER, and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with XTAMPZA ER. Clinical Considerations Infants exposed to XTAMPZA ER through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. 8.3 Females and Males of Reproductive Potential Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6.2), Clinical Pharmacology (12.2)]. 8.4 Pediatric Use Safety and effectiveness of XTAMPZA ER in pediatric patients below the age of 18 years have not been established. 8.5 Geriatric Use In controlled pharmacokinetic studies in elderly subjects (greater than 65 years) the clearance of oxycodone was slightly reduced. Compared to young adults, the plasma concentrations of oxycodone were increased approximately 15% [see Clinical Pharmacology (12.3)]. Of the total number of subjects entered into the titration phase of the Phase 3 study for XTAMPZA ER (740), 88 (12%) were age 65 and older. In this clinical trial with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were seen in the elderly patients who received XTAMPZA ER. Thus, the usual doses and dosing intervals may be appropriate for elderly patients. Use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, concomitant disease, and use of other drug therapy. Respiratory depression is the chief risk in elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of XTAMPZA ER slowly in geriatric patients [see Warnings and Precautions (5.6)]. 8.6 Hepatic Impairment A study in patients with hepatic impairment demonstrated greater plasma oxycodone concentrations than those seen at equivalent doses in persons with normal hepatic function. A similar effect on plasma oxycodone concentrations can be expected for patients with hepatic impairment taking XTAMPZA ER. Therefore, in the setting of hepatic impairment, start dosing patients at 1/3 to 1/2 the usual starting dose followed by careful dose titration. Use of alternative analgesics is recommended for patients who require a dose of XTAMPZA ER less than 9 mg [see Dosage and Administration (2.3)].

8.7 Renal Impairment In patients with renal impairment, as evidenced by decreased creatinine clearance (<60 mL/min), the concentrations of oxycodone in the plasma are approximately 50% higher than in subjects with normal renal function. Follow a conservative approach to dose initiation and adjust according to the clinical situation. Use of alternative analgesics is recommended for patients who require a dose of XTAMPZA ER less than 9 mg [see Clinical Pharmacology (12.3)]. 8.8 Sex Differences In pharmacokinetic studies with XTAMPZA ER, healthy female subjects demonstrate up to 20% higher oxycodone plasma exposures than males, even after considering differences in body weight or BMI. The clinical relevance of a difference of this magnitude is low for a drug intended for chronic usage at individualized dosages. In the Phase 3 clinical trial there was a greater frequency of typical opioid adverse events for females than males; there was no male/female difference detected for efficacy. 9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance XTAMPZA ER contains oxycodone, a Schedule II controlled substance. 9.2 Abuse XTAMPZA ER contains oxycodone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydromorphone, methadone, morphine, and oxymorphone. XTAMPZA ER can be abused and is subject to misuse, addiction, and criminal diversion [see Warnings and Precautions (5.1)]. The high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse. All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “Drug-seeking” behavior is very common to persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction. XTAMPZA ER, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful recordkeeping of prescribing information, including quantity, frequency, and renewal requests as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. Risks Specific to Abuse of XTAMPZA ER XTAMPZA ER is for oral use only. Abuse of XTAMPZA ER poses a risk of overdose and death. The risk is increased with concurrent use of XTAMPZA ER with alcohol and other central nervous system depressants. Abuse Deterrence Studies Summary The in vitro data demonstrate that XTAMPZA ER has physicochemical properties expected to make abuse by injection difficult. The data from pharmacokinetic and human abuse potential studies, along with support from the in vitro data, also indicate that XTAMPZA ER has physicochemical properties that are expected to reduce abuse via the intranasal route. The data from the oral pharmacokinetic studies of manipulated XTAMPZA ER demonstrated a lack of dose dumping with no increase in oxycodone levels compared to intact XTAMPZA ER. Although the results of the oral human abuse potential study showed a difference in the Drug Liking endpoint, there was no statistically significant reduction in the response to Take Drug Again. Therefore, it cannot be concluded that XTAMPZA ER has physicochemical properties that are expected to reduce abuse via the oral route. However, abuse of XTAMPZA ER by injection and by the nasal route of administration, as well as by the oral route is still possible.

Additional data, including epidemiological data, when available, may provide further information on the impact of the current formulation of XTAMPZA ER on the abuse liability of the drug. Accordingly, this section may be updated in the future as appropriate. XTAMPZA ER contains oxycodone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit, including fentanyl, hydromorphone, methadone, morphine, and oxymorphone. XTAMPZA ER can be abused and is subject to misuse, addiction, and criminal diversion [see Warnings and Precautions (5.1) and Drug Abuse and Dependence (9.1)]. 9.3 Dependence Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. XTAMPZA ER should not be abruptly discontinued [see Dosage and Administration (2.5)]. If XTAMPZA ER is abruptly discontinued in a physically dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms [see Use in Specific Populations (8.1)]. 10 OVERDOSAGE Clinical Presentation Acute overdosage with XTAMPZA ER can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations [see Clinical Pharmacology (12.2)]. Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to oxycodone overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxycodone overdose. Because the duration of reversal would be expected to be less than the duration of action of oxycodone in XTAMPZA ER, carefully monitor the patient until spontaneous respiration is reliably reestablished. XTAMPZA ER will continue to release oxycodone and add to the oxycodone load for 24 to 48 hours or longer following ingestion necessitating prolonged monitoring. If the response to opioid antagonists is suboptimal or only brief in nature, administer additional antagonist as directed in the product’s prescribing information. In an individual physically dependent on opioids, administration of the usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist. DEA ORDER FORM REQUIRED Healthcare professionals can telephone Collegium Pharmaceutical’s Medical Affairs Department (1-855-331-5615) for information on this product. Manufactured by: Patheon Pharmaceuticals, Cincinnati, OH 45237 Collegium Pharmaceutical, Inc. Canton, MA 02021 ©2016 Collegium Pharmaceutical, Inc. U.S. Patent Nos. 7,399,488; 7,771,707; 8,449,909; 8,557,291; 8,758,813; 8,840,928 and 9,044,398, and 9,248,195 This brief summary is based on Xtampza ER Prescribing Information, Revised 04/2016. PP-XT-US-0086

2 7 t h a n n u a l M E E T I N G s p e c i a l s e c ti o n

Welcome to the 27th Annual Meeting IN SAN ANTONIO For those of you who have joined us at the meeting, you can use these pages as a guide to the weekend. On the following pages, you will find:

• Full meeting agenda • Course summaries

• Exhibitor listings

If you are not with us this week, please check the Pain Care Learning Center at education.aapainmanage.org in October to access the outstanding content being presented this week.

l e a d e r s i n m u lti d i s c i p l i n a r y c a r e s i n c e 19 8 8 THE PAIN PRACTITIONE R

| VOLUME 26, NUMBER 4 |

2 0 1 6 m e e t i n g A GEN D A For full program descriptions, visit www.aapainmanage.org/annual-clinical-meeting The educational courses at the Annual Meeting are supported by an educational grant from Pfizer, Inc.

Pre-conference programs Wednesday, September 21 and Thursday, September 22 7:00 AM – 4:00 PM Advanced Credentialed Pain Practitioner (ACPP) Curriculum Review Course (15 credits)

Faculty: George D. Comerci, Jr., MD, FACP, ADAAPM; Brian M. Shelley, MD, ADAAPM; Daniel J. Duhigg, DO, MBA, ADAAPM Room: Cibolo 8-9 UAN: 0453-9999-16-208-L04-P

Thursday, September 22 9:00 AM – 4:30 PM Hands on Workshop: 3 Experts, 13 Muscles: How to Treat and Diagnose Myofascial Pain (7 credits) Faculty: Ben Daitz, MD; Lucy Whyte Ferguson, DC; Victoria L. Magown, CMTPT, LMT, RMTI Room: Cibolo 7 UAN: 0453-9999-16-212-L04-P

Eating for Healing: Evidence-Based Nutrition, Supplements, and Lifestyle Choices for Pain Patients (6 credits)

Faculty: Robert Bonakdar, MD; Nancy Cotter, MD, FAAPMR, FABIHM, FACN; Bryan White, PhD; Victor S. Sierpina, MD, ABFM, ABIHM Room: Cibolo 3-4 UAN: 0453-9999-16-211-L04-P

This activity is supported by an educational grant from Thorne Research, Inc.

Chronic Pain and Opioid Use: Best Practices in the Current Environment (6 credits)

Faculty: Paul Christo, MD; Brett Badgley Snodgrass, FNP-C, CPE, FACPP; Gary Reisfield, MD, Jennifer Bolen, JD Room: Cibolo 10-11

UAN: 0453-9999-16-207-L04-P This program is supported by an unrestricted educational grant from Adapt Pharma, Inc. This activity has been supported through an independent educational grant from Teva Pharmaceuticals.

conference sessions Thursday, September 22 Meeting Kick-off Activities 5:00-5:30 PM President’s Welcome

Joanna Katzman, MD, MSPH Room: Cibolo 5-6

1. Keynote The National Pain Strategy: Balancing Care and Risks Faculty: Linda L. Porter, PhD Room: Cibolo 5-6 UAN: 0453-9999-16-213-L04-P

5:30-6:30 PM

6:30-8:30 PM President’s Reception in the Exhibit Hall

Friday, September 23

2. Wake-Up Call: Morning Movement Faculty: Roger Mignosa, DO Room: Sunflower/Wisteria UAN: 0453-9999-16-214-L04-P

6:00-7:00 AM

6:30-8:00 AM

Sunrise Symposia

8:05-9:05 AM 3. Keynote Integrative Pain Management: Global Perspectives on How We Can Improve Pain Care Faculty: Robert Bonakdar, MD, FAAFP Room: Cibolo 5-6 UAN: 0453-9999-16-215-L04-P 9:10-10:10 AM 4. Multidisciplinary Approach to Back Pain Faculty: Christian Gonzalez, MD Room: Cibolo 8-11 UAN: 0453-9999-16-216-L04-P

| T H E PA I N PRACTITION ER | A U G U S T / S E P T E M B E R 2 0 1 6

5. Update on Complex Regional Pain Syndrome Faculty: Paul Christo, MD Room: Cibolo 7 UAN: 0453-9999-16-217-L04-P 6. Trauma and Pain: An Evidence-Based Connection Between the Emotional and Physical States Faculty: Donald D. McGeary, PhD Room: Cibolo 1-4 UAN: 0453-9999-16-218-L04-P 10:00 AM Exhibit Hall Grand Opening 10:15-11:15 AM Best Poster Awards & Poster Session 11:20 AM-12:20 PM 7. Myofascial Pain: A Brief History of the Present Illness & Trigger Point How-To Faculty: Ben Daitz, MD Room: Cibolo 8-11 UAN: 0453-9999-16-219-L04-P 8. Controlled Substance Prescribing: Steps You Can Take to Avoid Getting Voted Off Pain Island Faculty: Jennifer Bolen, JD Room: Cibolo 7 UAN: 0453-9999-16-220-L04-P 9. Taking the Haunt Out of the Phantom: Interdisciplinary Phantom Limb Pain Treatment Faculty: Benjamin M. Keizer, PhD; Jaime Clapp, PT, DPT, OCS; Marie Black, DPT Room: Cibolo 1-4 UAN: 0453-9999-16-233-L04-P 12:20-1:50 PM Advocacy Supported Lunch From Policy to Practice: How the CDC Guidelines Play out in Primary Care (non-cme) Faculty: Robert Twillman, PhD; Cindy Steinberg; Robert Rich Jr, MD, FAAFP Room: Grand Oaks Ballroom K, L, N-Q This is not a CME program. Supported by Teva Pharmaceuticals USA, Inc. 1:55-2:25 PM Short Shots: 30-Minute, Targeted Sessions 10. Osteopathic Pearls of Movement Faculty: Roger Mignosa, DO Room: Cibolo 8-11 UAN: 0453-9999-16-222-L04-P 11. Laughter is the Best Medicine Faculty: Jay Sandweiss, DO Room: Cibolo 7 UAN: 0453-9999-16-224-L04-P 12. Food for Thought: Can Diet & Nutrition Approaches Influence Pain? Faculty: Robert Bonakdar, MD, FAAFP Room: Cibolo 1-4 UAN: 0453-9999-16-223-L04-P 2:30-3:00 PM Short Shots: 30-Minute, Targeted Sessions 13. Osteopathic Pearls of Movement Faculty: Roger Mignosa, DO Room: Cibolo 8-11 UAN: 0453-9999-16-222-L04-P 14. Laughter is the Best Medicine Faculty: Jay Sandweiss, DO Room: Cibolo 7 UAN: 0453-9999-16-224-L04-P 15. Food for Thought: Can Diet & Nutrition Approaches Influence Pain? Faculty: Robert Bonakdar, MMD, FAAFP Room: Cibolo 1-4 UAN: 0453-9999-16-223-L04-P 3:05-4:05 PM 16. Keynote The Multidimensional Nature of Pain and Its Interfaces with Addiction: Implications for Treatment and Recovery Faculty: Seddon Savage, MD Room: Cibolo 5-6 UAN: 0453-9999-16-225-L04-P 4:10-5:10 PM 17. PLENARY Plenary: Non-Pharmacological Modulation of Chronic Pain Faculty: M. Catherine Bushnell, PhD Room: Cibolo 5-6 UAN: 0453-9999-16-226-L04-P 5:00 - 7:00 PM Exhibitors’ Reception in the Exhibit Hall

2 7 t h a n n u a l MEETING s p e c i a l s e c t i o n

S aturday,

September 24

6:00-7:00 AM 18. Wake-Up Call: Group Morning Meditation Faculty: Bruce Singer, PsyD Room: Sunflower/Wisteria UAN: 0453-9999-16-227-L04-P 6:30-8:00 AM Sunrise Symposia 8:05-9:05 AM 19. How I Learned to Stop Worrying and Love the Migraine Brain Faculty: Duren Michael Ready, MD, FAHS, ADAAPM Room: Cibolo 8-11 UAN: 0453-9999-16-228-L04-P 20. Short Term Dynamic Psychotherapy in the Treatment of Pain Syndromes Faculty: Jeff Katzman, MD Room: Cibolo 7 UAN: 0453-9999-16-229-L04-P 21. Interdisciplinary Treatment for the War on Comorbid CRPS and PTSD Faculty: Benjamin M. Keizer, PhD, and Justin Boge, DO, MS, DABA Room: Cibolo 1-4 UAN: 0453-9999-16-230-L04-P 9:10-10:10 AM 22. Refractory Migraine: Alternatives to Cursing God and Dying (When what you’re doing isn’t working) Faculty: Duren Michael Ready, MD, FAHS, ADAAPM Room: Cibolo 8-11 UAN: 0453-9999-16-231-L04-P 23. The Whole Story: Biopsychosocial Approach to the Assessment, Treatment, and Prevention of Chronic Pain Faculty: Robert J. Gatchel, PhD, ABPP Room: Cibolo 7 UAN: 0453-9999-16-232-L04-P 24. Integrative Medical Group Visits: An Innovative Model of Care for Patients with Chronic Pain Faculty: Paula Gardiner, MD Room: Cibolo 1-4 UAN: 0453-9999-16-221-L04-P 10:00-10:45 AM Coffee Break, Exhibits, and Hall Drawings 10:45-11:45 AM 25. The Elephant in the Room: Managing Pain Patients with Substance Use Disorders Faculty: Michael Sprintz, DO, FASAM Room: Cibolo 8-11 UAN: 0453-9999-16-234-L04-P 26. Incorporating Pain Management into Nursing Practice Curriculum Faculty: Jackie S. Rowles, DNP, MBA, CRNA, ANP-BC, FAAPM, FAAN Room: Cibolo 7 UAN: 0453-9999-16-235-L04-P 27. Managing Patients’ Expectations: SI Joint and Low Back Pain Faculty: Ron Andrews, PT, PhD Room: Cibolo 1-4 UAN: 0453-9999-16-236-L04-P 11:50 AM -1:20 PM Supported Lunch 1:25 - 1:55 PM Short Shots: 30-Minute, Targeted Sessions 28. Can Yoga Help Back Pain as Much as Physical Therapy? Faculty: Robert B. Saper, MD Room: Cibolo 8-11 0453-9999-16-237-L04-P 29. Integrating Massage Therapy into the Pain Practice Faculty: Nancy Porambo, MS, LMT Room: Cibolo 7 UAN: 0453-9999-16-238-l04-P 30. Guided Imagery for Pain Faculty: Bruce Singer, PsyD Room: Cibolo 1-4 UAN: 0453-9999-16-239-L04-P 2:00- 3:30 PM Exhibit Hall Closing Reception 2:00- 3:30 PM Shared Interest Groups (SIGs)

3:35 - 4:05 PM Short Shots: 30-Minute, Targeted Sessions 31. Can Yoga Help Back Pain as Much as Physical Therapy? Faculty: Robert B. Saper, MD Room: Cibolo 8-11 UAN: 0453-9999-16-237-L04-P 32. Integrating Massage Therapy into the Pain Practice Faculty: Nancy Porambo, MS, LMT Room: Cibolo 7 UAN: 0453-9999-16-238-L04-P 33. Guided Imagery for Pain Faculty: Bruce Singer, PsyD Room: Cibolo 1-4 UAN: 0453-9999-16-239-L04-P 4:10 – 5:10 PM 34. Musculoskeletal Pain: Is the Issue in the Tissue? Faculty: John E. Garzione, DPT Room: Cibolo 8-11 UAN: 0453-9999-16-241-L04-P 35. Fibromyalgia: Diagnosis and Treatment of a Prototypical Mind-Body Disorder Faculty: Catherine Vriend, PhD Room: Cibolo 7 UAN: 0453-9999-16-242-L04-P 36. Do’s and Don’ts: Safe Prescribing of OTC Analgesics Faculty: Shauna Pittman, PharmD Room: Cibolo 1-4 UAN: 0453-9999-16-243-L04-P 5:15-6:15 PM 37. Lessons Learned: Group Acupuncture in Primary Care Faculty: Melissa Diane McKee, MD, MS; Arya Nielsen, PhD Room: Cibolo 8-11 UAN: 0453-9999-16-244-L04-P 38. The Evolution of Fibromyalgia Faculty: Jay B. Higgs, MD Room: Cibolo 7 UAN: 0453-9999-16-245-L04-P 39. Protecting Your Patients from Drug Interactions Faculty: Shauna Pittman, PharmD Room: Cibolo 1-4 UAN: 0453-9999-16-246-L04-P

Sunday, September 25 6:00-7:00 AM 40. Wake-Up Call: Group Morning Meditation Faculty: Bruce Singer, PsyD Room: Sunflower/Wisteria UAN: 0453-9999-16-247-L04-P 7:00-8:00 AM Breakfast 8:00-9:00 AM 41. Integrative Pain and Symptom Management Strategies for the Cancer Patient Faculty: Larry C. Driver, MD Room: Cibolo 5 UAN: 0453-9999-16-248-L04-P 42. Community-Based Integrative Treatment Programs for Veterans and Military with Post-Traumatic Stress and Chronic Pain Faculty: Bob Deschner, MS, and Dottie Goodsun, MEd, EFT II Room: Cibolo 1-4 UAN: 0453-9999-16-249-L04-P 8:00 AM -1:25 PM 43. The Perfect Storm: Chronic Pain, Inflammation, and Dysfunctional Sleep (5 hours) Faculty: Art Roberts, DDS, MSc; Joseph Matthews, DDS; Juan F. Yepes, DDS, MD, MPH, MS, DrPH Room: Cibolo 6 UAN: 0453-9999-16-250-L04-P 9:05 AM-1:25 PM 44. Hands-On Workshop: Management of Amplified Pain Using Biofeedback (4 hours) Faculty: Raouf S. Gharbo, DO; Jay P. Ginsberg, PhD; Melanie E. Berry, MS, BCB, OMC, FAIS Room: Cibolo 5 UAN: 0453-9999-16-251-L04-P 45. Battlefield Auricular Therapy (4 hours) Faculty: COL Dean H. Hommer, MD, MBA, FAAPMR, FANEM Room: Cibolo 1-4 UAN: 0453-9999-16-252-L04-P THE PAIN PRACTITIONE R

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2016 Meeting Course Summaries We invited select faculty to submit their course summaries, key take-away points, and references to give you an overview of this year’s meeting content. If you are not with us in person, be sure to check our Pain Care Learning Center at education.aapainmanage.org to access the meeting content.

Three Experts, 13 Muscles: How to Treat and Diagnose Myofascial Pain Ben Daitz, MD, professor of family and community medicine at the University of New Mexico (UNM) School of Medicine, and an attending physician at the University Hospital’s chronic pain clinic and Project ECHO’s chronic pain and headache telemedicine clinic. Lucy Whyte Ferguson, DC, faculty member of the UNM Pain Center and a consultant with Project ECHO. Victoria Magown, CMTPT, LMT, owner/director of the Myofascial Rehabilitation Center, Ltd; co-founder of the American Institute for Myofascial Studies, LLC (2003-2012); and the primary instructor for MyoRehab Seminars, Albuquerque, New Mexico.

The three presenters of this course, all former students of Janet Travell, MD, have almost 100 years of combined experience treating myofascial pain (MFP). MFP is the most common primary cause of musculoskeletal pain, and contributes as a secondary factor in many pain conditions. Unfortunately, most medications are not effective in treating MFP, so learning the manual skills involved in MFP diagnosis and treatment is important, particularly in an effort to decrease opiate prescribing. Accurate diagnosis and skilled treatment of MFP is a necessary skill for most pain practitioners. Successful treatment of MFP depends on manual diagnostic skills, including

Sternocleidomastoid Pain Pattern

an understanding of referred pain from trigger points (TrPs), and understanding how to identify and eliminate perpetuating factors. This course, designed as an introduction to the development of these skills, and as a refresher for practitioners who already treat MFP, will focus on the diagnosis and treatment of 13 key muscles that are important clinically in MFP syndromes of the upper and lower body. The workshop will emphasize hands-on practice with coaching. It will also include instruction in specific stretches to elongate the taut bands that harbor myofascial TrPs. There will also be a review of recent research on MFP pathophysiology. Key “Take-Away” Points

1. Myofascial pain syndrome (MPS) is the most common cause of chronic pain. 2. Treating the site of pain is very often ineffective because of the phenomenon of referred pain from myofascial trigger points (TrPs) that are most often located at some distance from the site of pain. 3. In order to treat MPS, an understanding of muscle anatomy and the ability to accurately palpate TrPs is essential. In other words, skilled manual examination is the primary diagnostic process. 4. It is important to address perpetuating factors that include sources of mechanical irritation, sleep disturbance, hormonal imbalances, and concomitant medical conditions. This is one of the reasons that an integrated health care team is often the most effective in successfully treating individuals with complex MPS. Other important point: Participants can manage their own learning in this workshop by self-assessing their ability to identify TrPs in each of the 13 muscles presented. Coaching and hands-on practice are part of the workshop, so participants can work with coaches until they are sure they can identify the TrPs. References Chiarotto A, Clijsen R, Fernandez-de-Las-Penas C, Barbero M. Prevalence of myofascial trigger points in spinal disorders: a systematic review and metaanalysis. Arch Phys Med Rehabil. 2016 Feb;97(2):316-337. doi: 10.1016/j. apmr.2015.09.021. Epub 2015 Oct 17

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Rodríguez-Mansilla J, González-Sánchez B, De Toro García Á, et al. Effectiveness of dry needling on reducing pain intensity in patients with myofascial pain syndrome: a meta-analysis. J Tradit Chin Med. 2016 Feb;36(1):1-13. Simons DG, Travell JG, Simons LS. Myofascial Pain and Dysfunction: the Trigger Point Manual, Vol. 1, 2nd edition. Baltimore: Williams & Wilkins; 1999. Travell JG, Simons DG. Myofascial Pain and Dysfunction: the Trigger Point Manual, Vol. 2. Baltimore: Williams & Wilkins; 1992. Vidaković B, Uljanić I, Perić B, Grgurević J, Sonicki Z. Myofascial pain of the head and neck among Croatian war veterans treated for depression and posttraumatic stress disorder. Psychiatr Danub. 2016;Mar;28(1):73-76. Whyte Ferguson L, Gerwin R. Clinical Mastery in the Treatment of Myofascial Pain. Baltimore: Lippincott, Williams & Wilkins; 2005.

Non-Pharmacological Modulation of Chronic Pain M. Catherine Bushnell, PhD, scientific director, Division of Intramural Research, senior investigator, Pain and Integrative Neuroscience Branch (PAIN), National Center for Complementary and Integrative Health, Bethesda, Maryland.

Chronic pain has consequences that go far beyond the pain itself, with patients showing anxiety, depression, and cognitive deficits. Longitudinal studies of rodent models show similar changes. Brain imaging studies in both pain patients and rodents show alterations in brain anatomy and function. Nevertheless, we now see that these effects can be prevented or reversed by environmental factors. In pain patients, lifestyle choices, such as yoga or meditation, reduce pain perception and counter age-related decreases in brain gray matter. Rodent models show that increased stress alters pain behaviors, whereas enriched environments reduce such behavior and brain changes. Together, these data indicate that the far-reaching adverse effects of chronic pain may be reduced or prevented by environmental factors that could affect pain modulatory systems in the brain. Key “Take-Away” Points

1. Chronic pain has comorbidities, and this is also shown in animal models of chronic pain. 2. Chronic pain alters brain anatomy. 3. Practicing yoga seems to protect against age-related gray matter loss and increases pain tolerance. 4. Environmental enrichment in rodents reduces the impact of chronic pain. References Bushnell MC, Case LK, Ceko M, et al. Effect of the environment on the long-term consequences of chronic pai. Pain. 2015;Suppl 1: S42-49. Low LA, Millicamps M, Seninowicz DA, et al. Nerve injury causes long-term attentional deficits in rats. Neuroscience Lett. 2012;529:103-107. Seminowicz DA, et al. MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain. Neuroimage. 2009;47(3):1007-1014. Bushnell MC, Ceko M, Low LA. Nature Rev Neurosci. 2013;14:502-511. Villemure C, Ceko M, Cotton VA, Bushnell MC. Insular cortex mediates increased pain tolerance in yoga practitioners. Cereb Cortex. 2013;24: 2732-2740. Villemure C, Ceko M, Cotton VA, Bushnell MC.. Neuroprotective effects of yoga practice: age-, experience-, and frequency-dependent plasticity. Front Hum

Neurosci. 2015;12:9:281. Vachon P, Millecamps M, Low L, et al. Alleviation of chronic neuropathic pain by environmental enrichment in mice after the establishmet of chronic pain. Behav Brain Funct. 2013;7:9:22.

Short-Term Dynamic Psychotherapy in the Treatment of Pain Syndromes Jeffrey Katzman, MD, professor and vice chair for Academic and Clinical Affairs at the University of New Mexico, Albuquerque, New Mexico.

In this presentation, I will define psychodynamic psychotherapy and outline the evidence for its use in various psychiatric syndromes relative to other formats of psychotherapy. The evidence for the use of this format of psychotherapy in the treatment of pain will then be explored. Following a review of the evidence for this paradigm, the underlying theory belying this work will be presented. Videotaped presentations will illustrate the relationship between unexperienced emotions, anxiety, and psychological defenses. The talk will conclude with a presentation of the specific methodology employed when utilizing intensive short-term dynamic psychotherapy. Key “Take-Away” Points

1. Short-term dynamic psychotherapy is a highly effective tool in the treatment of multiple psychiatric syndromes. 2. Evidence demonstrates cost savings through appropriate use of short-term dynamic psychotherapy. 3. Evidence is emerging that short-term dynamic psychotherapy is helpful for patients suffering various pain syndromes. 4. The avoidance of emotional experiences can result in anxiety and psychological defenses, including somatic pain, which can lead to great suffering. References Chavooshi B, Mohammadkhani P, Dolatshahee B. Efficacy of intensive shortterm dynamic psychotherapy for medically unexplained pain: a pilot three-armed randomized controlled trial comparison with mindfulness-based stress reduction. Psychother Psychosom. 2016;85:123-125. Abbass A. The emergence of psychodynamic psychotherapy for treatment resistant patients: intensive short-term dynamic psychotherapy. Psychodyn Psychiatry. 2016;44(2):245-280.

Triangle of Conflict Defense

Anxiety

Impulse/Feeling

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The Biopsychosocial Assessment, Treatment, and Prevention of Chronic Pain Robert J. Gatchel, PhD, ABPP, Nancy P. and John G. Penson Endowed Professor of Clinical Health Psychology and Distinguished Professor of Psychology, University of Texas at Arlington.

The biopsychosocial model has been repeatedly demonstrated to be the most heuristic and comprehensive approach to the assessment and treatment of pain. This model conceptualizes pain as a dynamic and complex interaction among biological/ physical, psychological, and social factors that often perpetuates and may worsen the clinical presentation of pain. It also explains why there are frequent individual differences in the experience and expression of pain symptomatology. Three important areas will be reviewed: the biopsychosocial assessment of pain; the biopsychosocial treatment approach; and how this biopsychosocial approach has led to methods to prevent the transition of acute pain to chronic pain and disability. Two of the most prevalent musculoskeletal pain conditions will be discussed: chronic low back pain, which ranks number one as the most prevalent of these conditions, and temporomandibular joint and muscle disorder, which ranks second only to low back pain. We now have reliable methods to screen these patients at the acute stage to determine their “risk status,” and then provide early biopsychosocial intervention in order to prevent the development of chronicity. Examples of such programs will be presented. Key “Take-Away” Points

1. The biopsychosocial model is the most heuristic and successful approach to assessing and treating pain. 2. The two most prevalent musculoskeletal pain conditions are chronic low back pain and temporomandibular joint and muscle disorder. 3. We now successfully screen patients who are at “high risk” for developing chronic problems with these conditions. 4. There are successful early intervention programs for treating them. References Gatchel RJ. Clinical Essentials of Pain Management. Washington, DC: American

BIOPSYCHOSOCIAL MODEL Complex and Dynamic Interaction among Physiologic, Psychologic and Social Factors, which Perpetuates and May Worsen the Clinical Presentation

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Psychological Association Press; 2005. Gatchel RJ, Peng YB, Peters ML, Fuchs PN, Turk DC. The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull. 2007;133(4):581-624. Turk DC, Monarch ES. Biopsychosocial perspective on chronic pain. In: Turk DC, Gatchel RJ. (Eds.) Psychological Approaches to Pain Management: A Practitioner’s Handbook. 2nd ed. New York: Guilford; 2002. Zale EL, Ditre JW. (2015). Pain-related fear, disability, and the fear-avoidance model of chronic pain. Curr Opin Psychol. 2015; 5:24-30.

Incorporating Pain Management into the Nursing Educational Curriculum Jackie Rowles, DNP, MBA, CRNA, ANP-BC, FAAPM, FAAN, Marian University, Carmel, Indiana.

This lecture reviews the scope of the national pain problem; details learning objectives for acute pain management vs. chronic pain management; highlights use of the National Pain Strategy Team report as a beginning plan for adding pain curriculum to nursing educational content; and discusses the cooperative efforts of APRN organizations in formulating opioid use/disorder education. Key “Take-Away” Points

1. IOM report states need for all providers to have pain training CE and assessment for licensure, certification, and recertification. 2. Chronic pain curriculum is different than acute pain training. 3. HHS/NIH National Pain Strategy Team Report serves as a template for education. 4. Advanced Practice Nursing Organizations have pledged to develop joint online training on opioid use disorder and overdose. References Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America A Blueprint for Transforming Prevention, Care, Education, and Research. Washington (DC): National Academies Press (US); 2011.ISBN-13: 978-0-309-21484-1I NIH/HHS: Draft National Pain Strategy Report: A Comprehensive Population Health-Level Strategy for Pain http://iprcc.nih.gov/docs/DraftHHSNationalPainStrategy.pdf SBN-10: 0-309-21484-X The Pain Management Task Force Report. Office of the Army Surgeon General. Providing a Standardized DoD and VHA Vision and Approach to Pain Management to Optimize the Care for Warriors and their Families. 2010 https://www.apsoc. org.au/PDF/Research/1_US-DoD-Pain-Task-Force-Final-Report-May-2010.pdf American Association of Colleges of Nursing http://www.aacn.nche.edu/

SI Joint and Low Back Pain: Manual Therapy and Clinical Management Concepts Ronald P Andrews, PT, PhD, OCS, associate professor, department of orthopaedics and rehabilitation, Division of Physical Therapy, University of New Mexico School of Medicine, Albuquerque, New Mexico.

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The SI joint has been analyzed and studied extensively from an anatomical and biomechanical standpoint. There is little doubt that it can be a pain generator and that dysfunctions do occur. Despite this, there is still little clinical direction as to how to effectively manage patients who seem to fit the parameters of SI involvement. This straight forward manual therapy approach to identification and management will benefit practitioners as another effective tool in their respective tool kits. It is a fallacy that clinicians are treating the SI joint in isolation and therefore these interventions cannot be overly focused. Clinicians are evaluating and treating the lumbopelvic complex in addition to the remainder of the human interactive kinetic chain. For example, some people function at high levels with diagnosed hip labral tears and that imaging does not stand alone. Addressing impairments throughout the lower extremities and the lumbopelvic complex, on up to the upper cervical region will facilitate the highest level of ongoing success. That labral tear may have nothing to do with the patient’s current pain complaints. Again, clinicians do not treat the image, they manage the patient. Additionally and in this vein, this presentation will include the ongoing debate regarding the pathomechanical versus the biopsychosocial models relative to chronic spinal pain. How does one integrate these models in a multidisciplinary manner to best prevent the slide into chronicity? Key “Take-Away” Points

1. Demonstration of a very basic SI joint dysfunction screen and instituting 2 - 3 trial interventions. 2. The complexity and potential interactions of the lower extremity kinetic chain relative to lumbopelvic dysfunction. 3. The concepts of movement-based pain and function management in place of discussions about specific pain generators and pin point interventions. 4. The value of early intervention and chronic pain prevention strategies will be discussed. References Dijke GAH, Snijders CJ, Stoeckart R, Stam HJ. A biomechanical model on muscle forces in the transfer of spinal load to the pelvis and legs. J Biomech. 1999;32(9):927-933. Hossain M, Nokes LD. A model of dynamic sacro-Iliac joint instability from malrecruitment of gluteus maximus and biceps femoris muscles resulting in low back pain. Med Hypotheses. 2005;65(2): 278-281. Sembrano JN, Polly DW Jr. How often is low back pain not coming from the back? Spine. 2009; 34(1):E27-32. Takasaki H, Iizawa T, Hall T, Nakamura T, Kaneko S. The influence of increasing sacroiliac joint force closure on the hip and lumbar spine extensor muscle firing pattern. Man Ther. 2009;14(5):484-489. Hansen H, Manchikanti L, Simopoulos TT, Christo PJ, et al. A systematic evaluation of the therapeutic effectiveness of sacroiliac joint interventions. Pain Physician. 2012;15:E247-E278.

Integrating Massage Therapy into the Pain Practice Nancy M. Porambo, MS, LMT, Jim Thorpe, Pennsylvania, is a trustee on the Massage Therapy Foundation and also served as National President of the American Massage Therapy Association.

A 2015 national consumer survey conducted for the American Massage Therapy Association revealed 52% of all people who received massage therapy in the previous 12 months sought massage for injury, soreness, and pain or headache relief. The same survey indicated 16% of all people surveyed had discussed the possibility of massage therapy with their health care provider. Growing consumer demand coupled with substantive research that demonstrates the efficacy of massage therapy for a variety of health issues provides compelling reasons for health care providers to integrate massage therapy into the patient’s health approach. Massage therapy can be an important part of the treatment plan for a variety of health conditions. Current research finds massage therapy effective in the relief of chronic or acute pain, stress, and anxiety, and restorative for athletic and workplace injuries. It also improves sleep and provides benefit in palliative care. Utilizing massage therapy as part of an integrated care model can help ensure patients get the appropriate care to manage both the causes and symptoms of poor health, with the goal of improving outcomes. Massage therapy employs manual manipulation of soft tissues intended to promote health and wellbeing. A variety of massage therapy techniques and approaches are used to provide relief of soft tissue pain including neuromuscular, myofascial release, trigger point therapy, and Swedish massage. Understanding the source of certain chronic soft tissue pain, such as postural abnormalities and dysfunctional gait patterns, will help determine when massage therapy will be an effective choice in the treatment plan. Massage therapists work in a variety of settings from spas to health clubs to independent practices. Many tools are available to locate a qualified massage therapist who has the skills needed for specific treatment approaches. Ideally, when the massage therapist works collaboratively with the health care provider to ensure the patient receives an individualized care plan that addresses their specific needs, optimum results can be achieved. Key “Take-Away” Points

1. Forty-six states and the District of Columbia license or otherwise regulate massage therapists, define a scope of practice, and outline minimum standards for education. 2. Massage therapy is the manual manipulation of soft tissue intended to promote health and wellbeing and fits perfectly into the biopsychosocial model for patient care. THE PAIN PRACTITIONE R

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3. Recognition of improper posture and dysfunctional gait patterns can serve to avoid long-term pain conditions. 4. Health care providers and massage therapists should collaborate to address specific issues that their patients present.

Guided Imagery for Pain Bruce F. Singer, PsyD, chief of psychology for Crossroads Centre, Antigua, and founding director of the Chronic Pain and Recovery Center at Silver Hill Hospital, New Canaan, Connecticut.

Guided imagery (GI) is a mind-body therapy based on the theory of interaction between the mind, brain, body, and behavior. Popular mind-body therapies include mindfulness meditation, yoga, tai chi, biofeedback, progressive relaxation, hypnosis, and visual imagery. In contrast to mindfulness meditation, which generally focuses on cultivating selfcompassion and paying attention to the present moment in a non-judgmental fashion, GI incorporates a trained facilitator who talks you through a mental journey. Often there is a specific target or goal to GI, such as stress reduction, pain reduction, or headache relief. Mindfulness, by contrast, is process-oriented; placing a targeted goal on the experience is generally counterproductive (i.e., attempting to use a mindfulness meditation to relax may actually produce more stress when the goal is not immediately met). This short targeted presentation on GI for pain includes a brief discussion of the literature on the efficacy of utilizing GI for both cancer and non-cancer pain, as well as for depression and anxiety. Recent research demonstrates benefits for people with osteoarthritis but mixed medium-to-long term benefits for women with fibromyalgia. There are indications GI can be helpful with cancer pain as well. One study (Alam, 2016) attempted to see if GI during surgery with local anesthesia might help reduce pain and anxiety among patients but found, instead, that while it failed to do this to a significant level, it did help reduce anxiety in the surgeons themselves. This presentation offers participants the chance to experience two separate guided imagery scripts: the “Sandbag” meditation for pain reduction (Pincus, 2009) and a short A Centerpiece of Consciousness

guided imagery for headache reduction created by this writer and entitled “Clouds.” Key “Take-Away” Points

1. Demonstrate fundamental knowledge of the utility and limits to incorporating guided imagery into treatment of acute and chronic pain. 2. Discuss how to use a simple guided meditation for headache relief. 3. Discuss the differences between mindfulness meditations and guided imagery. References Baer SM, Hoffman AC, and Sheikh AA. Healing images: connecting with inner wisdom. In: A.A. Sheikh (Ed.) Healing Images: The Role of Imagination in Health. Amityville, NY: Baywood;2003:141-176. Pincus D, Sheikh A. Imagery for Pain Relief: A Scientifically Grounded Guidebook for Clinicians. New York: Routledge;2009. Alam M, Roongpisuthipong W, Kim NA, et al. Utility of recorded guided imagery and relaxing music in reducing patient pain and anxiety, and surgeon anxiety, during cutaneous surgical procedures: A single-blinded randomized controlled clinical trial. J Am Acad Dermatol. 2016; Apr 25.

Musculoskeletal Pain: Is the Tissue the Issue? A Physical Therapy Perspective John E. Garzione, PT, DPT, owner of Chenango therapeutics, Norwich, New York.

In this presentation, I will illustrate how and when anatomical dysfunction and central nervous system hypersensitivity contributes to the development and perpetuation of chronic musculoskeletal pain. Treatments for scar tissue, trigger points, neuro compression, central nervous system mediation, biomechanical and joint dysfunction will be individually discussed. Case studies will be presented. Key “Take-Away” Points

1. Demonstrate when tissue dysfunction is the sole cause of musculoskeletal pain. 2. Discus the role of central nervous system input into the pain experience. 3. Illustrate when a person has both tissue dysfunction and prolonged central nervous system input. 4. Illustrate how to integrate treatments to address both tissue and central nervous system hypersensitivity. References

 Imagination imagery is primary type of imagery used in guided imagery  Imagery is active not passive  It may be automatic or serve conscious goals  Imagery is intricately connected to one’s experience of one’s self  Imagery allows for exploration of the past (beyond sensory and short term memory) and projection into the future

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Apkarian AV, Hashmi JA, Baliki MN. Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain. 2011;152(3 suppl):S49-S64. Nicholas MK, George SZ. Psychologically informed interventions for low back pain: an update for physical therapists. Phys Ther. 2011;91(5):765-776. Ruscheweyh R, Verneuer B, Dany K, et al. Validation of the pain sensitivity questionnaire in chronic pain patients. Pain. 2012;153(6):1210-1218. Schreiber KL, Martel MO, Shnol H, et al. Persistent pain in postmastectomy patients: comparison of psychophysical, medical, surgical, and psychosocial characteristics between patients with and without pain. Pain. 2013;154(5):660-668.

Skeptical About Neurogenx? “I read all the scientific reports I could find and I was still a skeptic. Then I saw how well some patients did... NEUROGENX is definitely a viable neuropathy treatment where other options have failed.” - Steven Weinshel, JD, MD; Board Certified in Neurological Surgery

What Is the NEUROGENX Treatment?

It is a breakthrough electromedical treatment proven to effectively alleviate the pain, tingling, burning and numbness resulting from neuropathy and chronic nerve conditions. It can successfully help resolve neuropathy symptoms and nerve pain of varying intensities in different areas of the body. NEUROGENX patients have regained improved sensation, range of motion, balance and restful sleep as well as eliminated pain and numbness. The treatment is performed with a technologically advanced medical device called the NEUROGENX 4000PRO: it is FDA-Cleared and patented as the only device of its kind. The NEUROGENX Treatment is unlike any other currently available. It is non-narcotic, nonsurgical and non-invasive. It uses a sophisticated electronic signal with a wide frequency band to successfully treat neuropathy symptoms at the cellular level, helping to restore function and feeling.

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What do patients say about treatment with Neurogenx?

“I’m 61 years old and my diabetic neuropathy made my toes feel as if the skin had been sanded off with 80-grit sandpaper. During my 3rd Neurogenx treatment the muscles in my legs started tensing, flexing and moving - they came back to life! For the first time in years I could actually feel the rug under my feet!” (Todd W.) “Before I came to Neurogenx, my feet were swollen badly and I was in lots of pain. I had been suffering with neuropathy since the 1990s. It had gotten so bad that I couldn’t walk. Now the pain and swelling is all gone.” (H. Lann) “I’ve had neuropathy for 25 years, and after the first treatment I was able to move my feet and roll my toes in ways that I couldn’t since I was 40 years old. I’m grateful for this!” (W. Owen) “When I came to Neurogenx, my feet were numb and my balance was real bad….as far as the numbness is concerned, it is definitely a lot better. I can feel my feet when I walk. I can even tell cold versus hot and tile versus carpet. And I can feel my gas pedal now, which I couldn’t feel for a couple of years.” (E. Gereben)

Offer Your Patients Neuropathy and Nerve Pain Treatment with 87% Success Rate*! *87% reduction in symptoms is based on an April 2012 published medical study - you can read all the science behind the study in the Free Report. Offices following these protocols have seen similar results. Results may vary depending on age, condition, treatment compliance, genetics, diagnosis and other factors.

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Fibromyalgia: Diagnosis and Treatment of a Prototypical Mind-Body Disorder Catherine A. Vriend, PhD, chief of clinical health psychology service, department of behavioral medicine at Brooke Army Medical Center (BAMC), San Antonio, Texas.

Fibromyalgia syndrome (FMS) is a true mind-body disorder with bidirectional mechanisms that may promote its development and maintenance and account for the myriad and perplexing symptoms that patients experience. FMS symptoms respond to some medications and have some physiologically recognized underpinnings, but they are largely considered to have a substantial functional component. Like other chronic disease states, FMS appears to involve a genetic vulnerability that interacts with external and internal experiences and exposures. There is evidence of a sensory and pain processing dysfunction that includes augmentation of pain and other sensory stimuli that are then perceived as painful, failure of normal pain (and likely other sensory) inhibitory processes, and central sensitization. Deficits in cognition and deep sleep, as well as musculoskeletal pain and tenderness, and visceral hypersensitivity are accompanying features. Moreover, FMS involves an autonomic dysfunction associated with a persistently elevated sympathetic drive. The dysregulation of the autonomic nervous system generates many multi-system, “functional” symptoms, which are often major components of the overall symptom load these patients are experiencing. The diagnostic criteria do not address the autonomic dysregulation, but rather refer to some of the resulting complaints, such as headache, anxiety/depression, and irritable bowel syndrome. In actuality, dysphagia, reflux, irritable bowel syndrome, irritable bladder, cold sensitivity, uncomfortably cold hands and feet, myofascial pain disorder, night sweats, symptoms of anxiety, and panic attacks can all be caused by autonomic dysregulation. Symptoms of depression are an expected result for anyone experiencing loss of function and identity, persistent pain, Autonomic Response

Inhibitory

Affective

Failure

Response

FMS Augmented Pain Stimulus

Somato‐ Motor Response

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disturbed sleep, and negative interactions with providers. Understanding and validating these symptoms is essential to enlisting patients in any treatment program that includes behavioral modifications. These include exercise, sleep discipline, stress management, and psychotherapy to promote lifestyle change and address altered pain and sensory processing. A variety of approaches to decrease pain and increase function and wellbeing have been developed including cognitive behavioral therapy, acceptance and commitment therapy, mindfulness, emotion-focused therapy, and information therapy, which will be reviewed. Key “Take-Away” Points

1. Fibromyalgia syndrome (FMS) is not only chronic wide widespread pain. 2. A significant component of FMS is an autonomic nervous system dysfunction. 3. Failure to understand the nature of FMS prevents appropriate treatment and can even exacerbate the disorder. 4. There is a growing body of evidence that certain mindbody therapies can successfully treat FMS and there are various strategies which can greatly increase success. References Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014;311 15): 1547-1555. Kim J, Loggia ML, Cahalan CM, et al. The somatosensory link in fibromyalgia: functional connectivity of the primary somatosensory cortex is altered by sustained pain and is associated with clinical/autonomic dysfunction. Arthritis Rheum. 2015 May;67(5): 1395-1405. Perrot S, Russell IJ. More ubiquitous effects from non-pharmacologic than from pharmacologic treatments for fibromyalgia syndrome: a meta-analysis examining six core symptoms. Eur J Pain. 2014;18: 1067-1080.

Fibromyalgia Pathogenesis and Post-Traumatic Stress Disorder Jay B Higgs, MD, FACP, FACR, program director and a practicing rheumatologist at the San Antonio Military Medical Center, Fort Sam Houston, Texas.

Fibromyalgia syndrome (FMS) is a common source of pain. There is increasing interest in the intersection of fibromyalgia with post-traumatic stress disorder (PTSD). The STRONG STAR consortium offers a unique opportunity for study of FMS and PTSD in a military population. This presentation reviews the history and controversies of FMS and the rationale for considering the relationship between FMS and PTSD. Early results of the STRONG STAR epidemiologic studies show FMS prevalence of 2.9% in pre-deployment service members and 37% in service members seeking treatment for PTSD. Plans for further study of these populations will be discussed. Understanding the mutual influence of comorbid PTSD and FMS may lead to improved therapeutic strategies for each condition.

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PTSD and FMS?

PTSD

FMS

Key “Take-Away” Points

1. The long and controversial history of fibromyalgia provides important context for current research. 2. There are clinical and pathophysiologic rationales to consider fibromyalgia and post-traumatic stress disorder as comorbid conditions. 3. The STRONG STAR consortium offers a unique opportunity to study fibromyalgia and post-traumatic stress disorder in a military population. 4. The prevalence of fibromyalgia in service members with post-traumatic stress disorder is markedly higher than that of the pre-deployment population. References Perrot S. If fibromyalgia did not exist, we should have invented it. A short history of a controversial syndrome. Reumatismo. 2012;64(4):186-193. Wolfe F. Fibromyalgia wars. J Rheumatol. 2009;36(4):671-678. Liedl A, O’Donnell M, Creamer M, et al. Support for the mutual maintenance of pain and post-traumatic stress disorder symptoms. Psychol Med. 2010;40(7):1215-1223.

Workshop on Management of Amplified Pain due to Central Sensitization Using Autonomic Self-Regulation:

Heart Rate Variability Biofeedback and Mindfulness Ron Gharbo, DO, clinical faculty member at Eastern Virginia Medical School, Newport News, Virginia. JP Ginsberg, PhD, licensed clinical psychologist and neuropsychologist at the Dorn VA Medical Center, Columbia, South Carolina. Melanie Berry, MS, BCB, BCBS, FAIS, clinical director at Carolinas Biofeedback Clinic, Charlotte, North Carolina.

This workshop fosters understanding of how heart rate variability biofeedback (HRVB) and Mindfulness–Based Stress Reduction (MBSR) together empower patients with centrally sensitized pain to self-regulate and normalize sympathetic over-arousal of the autonomic nervous system (ANS) safely and comfortably. We will explain how HRVB brings about “left foot braking at the sino-atrial node,” and the empirically measurable benefits these two processes have in pain reduction. Through lecture, illustrations with data, interactive discussion, case reports, and hands-on workshop, attendees will develop familiarity with the advancing technologies and

therapies making ANS science a simple, powerful, and effective tool in the pain clinic. The course includes an exciting individual live demonstration of an HRV Biofeedback training session as well as hands-on experiences for attendees. The literature supporting HRVB as an integrative health intervention in general has grown substantially in just the past two decades. Resonant RSA, or Coherent HRV, improves physical health and emotional resilience by enlarging the range of autonomic system function driving the sympathetic-parasympathetic influences on the heart. The beneficial use of HRVB for pain management has been studied and documented by several clinical researchers. Awareness of this knowledge should propel the use of HRV parameters and HRVB for pain management assessment and treatment, as well. Durable versatile handheld commercial biofeedback devices have become easily available, making a prescription of resonant RSA 10 minutes BID and PRN a reasonable clinical Workshop practice. Management of Amplified Pain due to Central Sensitization usi Chronic pain sufferers crave being pain free, have racing Autonomic Self‐Regulation: Biofeedback and Mindfulness brain insomnia, and feel helpless due to kinesophobia (fear of movement). FearWhen we have chronic pain we ju avoidance of pain leads want it to go away. Heart Rate to catastrophizing, the Variability Biofeedback corrects single strongest predicimbalances in the autonomic ner tor of post-surgical pain. system caused by chronic pain. B Fear provokes the symlearning self‐regulation of ANS ac pathetic nervous system pain sufferers effectively control fight or flight response pain. Mindfulness ‐ paying atten while positive emotions purposefully and without judgme activate the parasympahelpful in the management of ch thetic nervous system. pain because it provides the key Engaging the positive learning to live with pain rather t emotions both volitionfearing, avoiding, or eradicating i ally and consciously to augment the amplification of HRV is another central component of HRVB. We ought not pay more attention with negative emotions to our pain, but we do. Mindfulness is “paying attention purposefully and without judgment.” Mindfulness is helpful in the management of chronic pain because instead of focusing with intense emotion, and to the exclusion of all other awareness on how badly want the pain to stop, we pay attention to our pain moment-to-moment, non-judgmentally, and even with curiosity. The key is learning to live with pain rather than fearing, avoiding, or eradicating it. This is what we call “ANS regulation.” Key “Take-Away” Points

1. HRV biofeedback and mindfulness are integrative health care techniques for self-regulation of the autonomic nervous system that are easily learned, non-invasive, non-pharmaceutical chronic pain interventions that can be can be easily THE PAIN PRACTITIONE R

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incorporated with other medical approaches to pain management. 2. HRV is a simple and quantified biomarker of physical and psychological health and disorder; HRV Coherence occurs when there is resonance throughout physiological systems. 3. Mindfulness is helpful in managing chronic pain because it enables pain patients to pay attention to pain momentto-moment and non-judgmentally rather than fearing or avoiding it. 4. A live demonstration and hands-on experience will give attendees a clear understanding of HRV biofeedback training. References Berry ME, Chapple IT, Ginsberg JP, Gleichauf KJ, Meyer J.A, Nagpal ML. Nonpharmacological intervention for chronic pain in veterans: a pilot study of heart rate variability biofeedback. 2014. http://dx.doi.org/10.7453/gahmj.2013.075. doi:10.7453/gahmj.2013.075 Kaiser RS, Mooreville M, Kannan K. Psychological Interventions for the Management of Chronic Pain: a Review of Current Evidence. Curr Pain Headache Rep. 2015;19(9):43. Zeidan F, Martucci KT, Kraft RA, Gordon NS, McHaffie JG, Coghill RC. (2011). Brain mechanisms supporting the modulation of pain by mindfulness meditation. J Neurosci. 2011;31(14):5540-5548. doi:10.1523/JNEUROSCI.5791-10.2011

Battlefield Auricular Acupuncture Col. Dean H. Hommer, MD, MBA, FAAPMR, FAANEM, chief, Department of Pain Management, San Antonio Military Center, Ft. Sam Houston, Texas.

The purpose of this training course is to teach interested medical personnel a simple and limited acupuncture technique called battlefield acupuncture (BFA). It harnesses the power of the auricular micro-system to quickly and effectively treat a variety of pain problems commonly encountered in a busy clinical practice. Developed in 2001 by Dr. Richard Niemtzow while serving in the United States Air Force, BFA has been employed effectively across the military and the Veterans Affairs health care system to treat a broad variety of pain complaints. Although acupuncture is not a new therapeutic approach to patient care, its incorporation into traditional practice is a relatively recent phenomenon. Originating in China, acupuncture has been used as a medical treatment for more than 5,000 years. Researchers around the globe are beginning to uncover the mechanisms of acupuncture’s effectiveness. Armed with a growing understanding of chronic pain and its relation to neurotransmitters, functional MRI studies of the brain, and more detail about the local effects of acupuncture needles, these researchers are developing an evidence-based picture of how acupuncture works. While acupuncture is commonly thought of as the application of dozens of needles at various points on the trunk of the body and/or its extremities, there are subsets of acupunc-

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ture practice emphasizing more limited and focused needle application. Examples include scalp acupuncture, hand acupuncture, and ear acupuncture (auriculotherapy). There is scientific evidence indicating that there is somatotopic correspondence between regions on the ear and activities in the central nervous system—and that therapeutic benefit is derived distantly when these ear zones are treated to relieve pain and other symptoms. Key “Take-Away” Points

1. BFA can be effective for any pain. 2. BFA should not be used if the source of pain is in question. 3. BFA training does not give you the credentials to perform any other type of auricular or other acupuncture. 4. If you find BFA useful, you may find further study to attain acupuncture credentialing particularly beneficial.

The Perfect Storm: Chronic Pain, Inflammation, and Dysfunctional Sleep Art Roberts, DDS, MSc, adjunct associate professor of oral medicine in the department of oral and maxillofacial pathology, medicine, and radiology at Indiana University School of Dentistry; and adjunct faculty of anesthesiology, critical care, and pain management at The College of Medicine and Veterinary Medicine, University of Edinburgh, UK.

Altered neuromatrix status often presents clinically as dysfunctional sleep, elevated inflammatory response, and chronic pain. Understanding the multivariate factors that can influence the neuromatrix is critical to accurate diagnosis, efficacious therapy, and improved outcomes. Key “Take-Away” Points

1. Persistent microglial irritation alters pain processing. 2. Dysfunctional sleep is a common etiological agent for microglial irritation/inflammation. 3. Altered pain processing will bias normal functioning of the immune, endocrine, and circadian systems.

Obstructive Pediatric Sleep Disorders: Relationship with Growth, Cognitive Development, and Chronic Pain Juan F. Yepes DDS, MD, MPH, MS, DrPH, associate professor in the department of pediatric dentistry at Indiana University School of Dentistry and attending at Riley Children Hospital in Indianapolis, Indiana.

In this presentation, I will provide up-to-date information on the emerging field of obstructive pediatric sleep disorders and

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their relationship with growth, cognitive development, and chronic pain. I will include cases to illustrate the learning and provide a format for discussion. Key “Take-Away” Points

1. Understanding the pathophysiology of OSA in children. 2. Understanding the diagnosis of OSA in children. 3. Discussing the consequences of OSA in children.

Community-Based Integrative Treatment Programs for Veterans and Military with Post-Traumatic Stress and Chronic Pain Bob Deschner, MS, is a classically trained research chemical engineer/ chemist who spent the last 25 years investigating innovative models of the autonomic nervous system and integration of evidence-based nutritional, energy, and natural healing modalities. Dottie Goodsun, MEd, co-founder of Vet TRIIP (Team Recovery Integrative Immersion Process) integrative programs for veterans, service members, and their families living with post-traumatic stress and chronic pain, San Antonio, Texas.

This presentation lays out the theory and models behind the innovative Vet TRIIP multimodality, complementary, and integrative immersion programs for veterans living with post traumatic stress and chronic pain from a perspective of the autonomic nervous system (ANS) and polyvagal theory. It also describes the evolution of the volunteer-based Vet TRIIP programs into their current format. The presentation will include the characteristics of military post traumatic stress disorder (PTSD) and the differences and similarities between military and other types of PTSD; how the sympathetic (fight or flight response) and parasympathetic (relax, rest and digest) branches of the ANS link the brain and body responses to the human stress response, chronic stress responses such as PTSD, and chronic pain syndromes such as nociceptive, neuropathic and inflammatory pain. Then they will give examples of how new insights into the freeze response and other aspects of the ANS from the polyvagal theory developed by Stephen Porges, PhD, were used to guide their development of the Vet TRIIP Integrative Immersion Process (IIP) programs to promote relaxation, more comfort and better sleep. In addition, they will describe their observations that a state of profound relaxation may reset the veteran’s stress responses and may enhance engagement with and benefits from traditional talk therapy and medications. The Vet TRIIP integrative programs have been offered to more than 1,000 veterans in San Antonio, Texas, since January, 2012.

Key “Take-Away” Points

1.Military post-traumatic stress disorder (PTSD) differs from sexual, childhood, incidental, and repetitive PTSD by the amount of intentional stress conditioning in warrior training and the intense reinforcement that occurs during combat and war experiences versus the hormonal and developmental aspects of sexual and childhood trauma and the duration, repetition, and range of intensity of exposure for incidental trauma and repetitive trauma (compassion fatigue). 2. The two branches of the autonomic nervous system (ANS)—the fight or flight response of the sympathetic nervous system (SNS) and the relax, rest, and digest response of the parasympathetic nervous system (PNS)—play important roles in linking the stress responses of the brain and body, chronic stress responses such as PTSD as well as the intensity of and recovery from the three types of chronic pain syndromes: nociceptive, neuropathic, and inflammatory pain. 3. The polyvagal theory model offers novel insights into a third branch of the ANS which governs the freeze response, suggesting additional options for shifting traumatic memories from amygdala-based, extinction-resistant memories to hippocampus-based memories that are more easily subject to modification and reconsolidation. 4. Vet TRIIP has pioneered novel community-based, multimodality, Integrative Immersion Process (IIP) Sessions offered on a periodic basis, adapted from the full-time integrative treatment programs at Fort Bliss (the Restoration and Recovery Program, John Fortunato, PhD) and Fort Hood/ DAMC (the Warrior Combat Stress Reset Program, Jerry Wesch, PhD). The goals of the Vet TRIIP IIP Sessions are to promote relaxation, more comfort, and better sleep. Successful immersion programs create integrative synergy to induce a state of profound relaxation which may temporarily reset the veteran’s stress responses and enhance engagement with and benefits of traditional programs. References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Washington, DC American Psychiatric Publishing; 2013. National Center for PTSD, U.S. Department of Veterans Affairs. DSM-5 Criteria for PTSD. BrainlLine Military.

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http://www.brainlinemilitary.org/content/2014/06/ dsm-v-tr-criteria-for-ptsd.html 2015. Accessed July 10, 2016. VA/DoD Clinical Practice Guidelines: Management of Post-Traumatic Stress Disorder and Acute Stress Reaction. U.S. Department f Veterans Affairs. http://www.healthquality.va.gov/guidelines/MH/ ptsd/ January 26, 2016. Accessed July 9, 2016. Porges SW. The Polyvagal Theory: Neurophysiological Foundations of Emotions, Attachment, Communication, and Self-Regulation. New York City: W. W. Norton; 2011. Libretto S, Hilton L, Gordon S, Zhang W, Wesch J. Effects of integrative PTSD treatment in a military health setting. Energy Psychol J. 2015;7(2)33-44. doi:10.9769/EPJ.2015.11.1.SL Engel CC, Cordova EH, Benefec DM, et al. Randomized effectiveness trial of a brief course of acupuncture for posttraumatic stress disorder. Med Care. 2014;Dec;52(12 Suppl 5):S57-64. doi: 10.1097/MLR. 0000000000000237

Pre-meeting program:

conventional thinking about the nature of chronic pain and depression is flawed According to Dr. Gary Kaplan, conventional thinking about the nature of chronic pain and depression is essentially flawed. Although physicians continue to diagnose conditions like migraines, fibromyalgia, chronic fatigue, chronic back pain, depression, anxiety, and PTSD, a growing body of research shows that these are in fact symptoms of something else— a deep-rooted inflammation in the brain. This inflammation can affect the nervous system for months—even years— to devastating effect.

TOTAL RECOVERY by Dr. Gary Kaplan is available wherever books and e-books are sold. Or visit: www.kaplanclinic.com

Role of Microbiome and DNA testing in Pain Management (Interstitial Cystitis/ Pelvic Pain) Bryan A. White, PhD, professor of animal sciences in the Carl R. Woese Institute for Genomic Biology, and director of the Mayo Clinic and University of Illinois Strategic Alliance for Technology-Based Healthcare, Urbana, Illinois.

Patients with urologic chronic pelvic pain syndromes (UCPPS) suffer chronic pelvic pain and dramatically lower quality of life, yet diagnostic markers and effective therapies remain elusive for these costly syndromes. Interstitial cystitis/bladder pain syndrome (IC/BPS or IC) is a debilitating UCPPS condition of pelvic pain and voiding dysfunction that afflicts as many as 8 million U.S. women, for whom depression is a common co-morbidity. IC etiology remains unknown, but urothelial lesions and lamina propria mast cells are associated with patient symptoms, and no effective therapies or diagnostic markers exist. Men with chronic prostatitis/ chronic pelvic pain syndrome are similarly afflicted. Many potential UCPPS mechanisms have been studied—including infection, inflammation, neurogenic dysfunction, and

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hypothalamic-pituitary-adrenal axis dysregulation—but no mechanism is associated with more than a subset of patients. Against this enigma of UCPPS mechanisms, however, is the recent appreciation that the microbiome drives health and disease. Individual species within the microbiome have recently been associated with driving disease through altered innate or altered pharmaceutical metabolism. Despite these advances, it remains unclear whether the microbiome contributes to pain syndromes generally and to UCPPS in particular. Studies have identified an association between fungi and symptom flares, but a signature UCPPS urinary microbiome has not yet been found that is associated with baseline symptoms. In collaboration with Anthony Schaeffer, MD, and David Klumpp, PhD, at Northwestern University, we recently defined bacterial pain phenotypes in murine UTI, where transient bladder infection can elicit a spectrum of pain responses, including chronic pelvic pain. Because pelvic pain is subject to modulation via organ crosstalk, we hypothesized that the GI and/or reproductive tract microbiome modulates IC pelvic pain. We characterized vaginal and fecal flora of IC patients and controls using Human Microbiome Project protocols. Vaginal samples were unremarkable, but IC fecal microbiome samples differed significantly from those from controls. Quantitative PCR of stool DNA with speciesspecific primer pairs demonstrated significantly reduced levels of Eggerthella sinensis, Collinsella aerofaciens, Faecalibacterium prausnitzii, Odoribacter splanchnicus, and Lactonifactor longoviformis in the microbiome of IC patients. These species, deficient in IC pelvic pain (DIPP), were further evaluated by receiver-operator characteristic (ROC) analyses, and

DIPP species emerged as potential IC biomarkers. Stool metabolomic studies identified glyceraldehyde as significantly elevated in IC. Metabolomic pathway analysis identified lipid pathways, consistent with predicted metagenome functionality. Together, these findings suggest that DIPP species and metabolites may serve as candidates for novel IC biomarkers in stool. Functional changes in the IC microbiome may also serve as therapeutic targets for treating chronic pelvic pain.

When Pain is More Complicated Turn to Sierra Tucson

Key “Take-Away” Points

1. The microbiome can influence the pain phenotype. 2. Pain is subject to modulation via organ crosstalk. 3. Multi-omics studies of the microbiome can likely yield new, important insights for UCPPS. 4. The IC microbiome may serve as a therapeutic target for treating chronic pelvic pain through nutrition or probiotics.

Every patient you see presents his or her own unique challenges. Yet regardless of your best efforts, sometimes you know that he or she may need more. There may be a host of underlying issues complicating their situation and stalling them in an endless cycle that may seem unbreakable. That’s when a team approach can help. We invite you to partner with Sierra Tucson so that together your patients can undergo a transformation that delivers them back to you prepared to continue successful treatment.

References Rudick CN, Billips BK, Pavlov VI, Yaggie RE, Schaeffer AJ, Klumpp DJ. Host-pathogen interactions mediating pain of urinary tract infection. J Infect Dis. 2010;201(8):1240-1249. Malykhina AP. Neural mechanisms of pelvic organ cross-sensitization. Neuroscience. 2007;149(3):660-672. Braundmeier-Fleming A, Russell N, Yang W, et al. 2016. Stool-based biomarkers of interstitial cystitis/bladder pain syndrome. Sci Rep. 2016;6:26083.

Call to learn more about our Pain Recovery Program including: • Residential approach with 3-6 week stay • Full physical and psychological assessment • Functional restoration program • Psychological and emotional support • Safe medication and non-medication strategies • Pain management education • Experienced, full-time, dedicated team • Board-certified Physiatrist • Dedicated Counselor • Physical Therapist

Annual Clinical Meeting September 21-25, 2016 The only clinical meeting dedicated exclusively to integrative pain management For more information, go to meeting.aapainmanage.org

• Integrative therapies

844-215-1400

• Lifestyle skills building • 24-hour support

SierraTucson.com

Sierra Tucson is accredited by The Joint Commission and licensed as both a special hospital and a behavioral health residential treatment center.

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2016 Meeting EXHIBITOR LISTINGS 1st Providers Choice Booth #400 www.1stproviderschoice.com Pain Management EMR and Practice Management Software. Physical Medicine and Pain providers are saving a lot of clinical documentation time by having Pain Management specific EMR Software and a Pain Management specific Patient Portal. Stop by the booth for your demonstration and details on the show special. Adapt Pharma Booth #307 www.adaptpharma.com Adapt Pharma is an innovative small business focused on developing cutting-edge treatments for patients with special medical conditions. Our product, NARCAN® Nasal Spray, is the first and only FDA-approved nasal naloxone that requires no assembly, no specialized training, and is needle-free. Please visit www. narcannasalspray.com for more details and full prescribing information. Admera Health Booth #418 www.admerahealth.com Admera Health is a CLIA-certified CAPaccredited laboratory, utilizing next-generation sequencing technology to advance the field of personalized medicine. Our expertise includes pharmacogenomics testing. Test results are delivered to physicians and patients in a distilled and manageable report, giving them the relevant information to make more informed treatment decisions. Aeon Global Health Booth #411 www.aeonglobalhealth.com Aeon Global Health’s mission is to lead a revolution in prevention, diagnosis, and treatment of diseases by providing health care providers with clinically actionable information that promotes patient centric, personalized medical care. Our services include cancer genomics, pharmacogenomics, toxicology, cystic fibrosis, and health technology applications. AIS PainCare Booth #501 www.aispaincare.com AIS Pain Care is the industry leader in injectable medications for patients with implanted intrathecal pain pumps. Founded in 1998 and serving over 16,000 pump patients from our state-of-the-art pharmacy and clean room at AIS headquarters in Jackson, Mississippi, AIS is USP 797 compliant and licensed to provide medications to all 50 states.

American Screening Booth #421 www.americanscreening.com American Screening, LLC is an ISO 13485 point-of-care manufacturer/distributor specializing in FDA, OTC/CLIA waived rapid drug test cups and dips, selling worldwide to 27 countries. We also sell saliva drug tests, alcohol, HCG, H. Pylori, Strep A, Flu A/B, FOB, Chlamydia, HIV, HBV, and HCV. sales@americanscreeningcorp.com Phone: 1(866)526-2873 Aprima Medical Software Booth #413 www.aprima.com Aprima offers innovative EHR, PM, and RCM solutions for pain management practices. Aprima auto-learns treatment plans for your most common patient complaints, making it easy to document procedures and injections. Electronic prescribing, including controlled substances, drives efficiency for providers and patients alike. For more info, please visit us at www.aprima.com. Aspen Medical Products Booth #313 www.aspenmp.com Aspen Medical Products is a leader in the development of innovative spinal bracing for post-trauma stabilization, pre-and-post surgical stabilization, pain management, and longterm patient care. Aspen Medical Products offers multiple orthotic options that provide unsurpassed motion restriction, superior comfort, and an economic advantage, encouraging better patient compliance. AVAZZIA Booth #507 www.epmfour.com Avazzia, Inc. designs and manufactures portable microcurrent medical devices for pain relief without drugs or surgery. Not all microcurrent is the same; Avazzia technology produces unique multi-phase, high-voltage, microcurrent, pulses for effectiveness. Professional and patient devices are US FDA-cleared and available internationally to help reduce dependence on opioids. Boiron Booth #417 www.boironusa.com Boiron, world leader in homeopathic medicines, is an $852 million public company with 3,700 employees and distribution in 59 countries. It is best known for Oscillococcinum®, a top-selling flu medicine, and its Arnicare® line of pain relievers.

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Bull Publishing Booth #410 www.bullpub.com Just released: The Opioid-Free Pain Relief Kit: 10 Simple Steps to Ease Your Pain by Dr. Beth Darnall, pain psychologist, Stanford University. This brief book teaches patients how to self-manage pain so they need less medication. Visit our table for a free review copy while supplies last. Includes relaxation CD. Carolina Liquid Chemistries Corp Booth #213 www.carolinachemistries.com Carolina Liquid Chemistries provides instruments, reagents, and service contracts for your drug testing screens for all size laboratories. Along with refurbished Olympus analyzers and reagents, CLC offers newer, technologically advanced analyzers: the CLC6410, CLC1600, and CLC800. CLC is an established FDAregistered, ISO-certified, and veteran-owned company with its own service organization, customer training center, and no charge support hotline to support its valued customers. Celluma - BioPhotas, Inc. Booth #406 www.biophotas.com BioPhotas, Inc. manufacturers the Celluma series of award-winning, FDA-cleared LED devices used to treat skin, muscle, and joint conditions including acne, wrinkles, and pain. Celluma is affordable, portable, and handsfree. The series consists of the flag-ship Celluma PRO, the stand-mounted Celluma ELITE, and the Celluma LITE for home use. Chart Logic, Inc. Booth #516 www.chartlogic.com ChartLogic offers a full ambulatory EHR suite, including EMR, practice management, e-Rx, patient portal, as well as offering complete medical billing services. Pain management specialists choose ChartLogic for its proprietary command-and-control methodology that allows users to create notes fast and efficiently. Start saving time and money today! Clarity Research Booth #522 www.crsciences.com Clarity Science is a leading international scientific research organization that performs rigorous research in the field of health care across a myriad of therapeutic areas. We conduct IRBapproved clinical research studies in the areas of pain management, scar and burn treatment, allergy, toxicology, GERD and more.

The education you need, when you want it.

• AIPM’s Pain Care Learning Center offers comprehensive on-demand integrative pain management education. • CME/CEU for physicians, nurses and psychologists with additional accreditations being added as available. • Basic content free for AIPM members and at a nominal fee for nonmembers. New programs are offered monthly!

Two current specialty programs are now offered: The 27th Annual Meeting Sessions Beginning in November you will be able access the meeting content online! Meeting attendees will receive a code after the meeting to access the programs as part of their registration fee for up to one year. If you did not attend the meeting, you can purchase individual courses for $29/hr. for members and $31/hr. for non-members. There are also options to purchase bundled courses at a lower price. for details, Visit: education.aapainmanage.org

To get started, go to: education.aapainmanage.org

Curriculum Review Course

or For more information: contact Cathleen Coneghen at cconeghen@aapainmanage.org

This thorough, 14-hour program, based on the curriculum for the Advanced Credentialed Pain Practitioner (ACPP) program, identifies and discusses the fundamental concepts and key topics needed to successfully evaluate and treat patients with chronic pain. for details, Visit: education.aapainmanage.org

Save $150 if you sign up for the online course and the ACPP exam at the same time. for details, Visit: aapainmanage.org, or call (209) 288-2205

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Complete Medical Services Booth #408 www.completemedicalservices.com Complete Medical Services, your C-Arm expert with 18 years of experience refurbishing OEC brings you Best Valued C-Arm in the market, ZEN-7000. The ZEN-7000 by Genoray offers a NEW C-Arm with more robust features without the premium price. ZEN-7000 comes with 30FPS, complete digital system, and flat screen monitors with excellent image quality and much more. Confirm BioSciences Booth #301 www.ConfirmBiosciences.com Confirm BioSciences offers a full range of drug and alcohol test kits for urine, saliva, and hair testing as well as laboratory services. Our industry best customer service and value-focused solutions are here to support all of your drug testing needs. ConTEXT MEDIA HEALTH www.contextmediahealth.com ContextMedia:Health is the leading provider of digital education solutions at the point of care. ContextMedia:Health’s comprehensive suite of products, including the Waiting Room TV, Exam Room Tablet, Patient Wifi and Digital Exam Room Wallboard, drives a more robust dialogue between physicians and patients to improve patient health outcomes. Depomed Booth #212 www.depomed.com Depomed is a leading specialty pharmaceutical company focused on enhancing the lives of the patients, families, physicians, providers, and payers. Depomed commercializes six innovative products for pain- and neurology- related disorders including indications of mild-to-severe acute pain, moderate to severe chronic pain, neuropathic pain, migraine, and breakthrough cancer pain. Designs for Health Booth #216 www.designsforhealth.com Designs for Health is a family-owned professional brand, offered exclusively to health care

professionals and their patients. For 25 years, we have been the health care professional’s trusted source for research-backed nutritional products of superior quality. By providing comprehensive support through our product line, clinical education, and practice development programs, we maximize the potential for successful patient treatment outcomes. Doctors Supplement Store Booth #304 www.doctorssupplementstore.com Doctors Supplement Store offers the easiest and most profitable way to get the supplements you recommend into your patients’ hands. We set up your personalized web store, patients order online or call toll-free, and we take care of the rest. Fast, FREE and easy set-up! Over 175 professional brands available. Dolor Technologies, LLC Booth #419 www.sphenocath.com Dolor Technologies is the inventor of the patented SphenoCath® device, a first of its kind FDA-registered nasal catheter used to administer anesthetics for SPG/PPG/trigeminal nerve blocks which have been shown to be effective in treating migraine, cluster, trigeminal neuralgia, and other TAC (trigeminal autonomic cephalgia) and atypical facial pain syndromes. Dr. First Booth #318 www.drfirst.com DrFirst pioneers software solutions and services that provide real-time access to patient data, improve communication and collaboration at the point of care and across the patient’s circle of caregivers, and enhance the doctor’s clinical view of the patient to help drive better health outcomes. Dr. Fuji/ACIGI Booth #222 www.fujichair.com Dr. Fuji Cyber-Relax massage equipment is the fruit of further evolution of intelligent pneumatic and mechanical technology designed to partner with medical and health professionals in their clinical stress management.

DrugScan Booth #404 www.DrugScan.com Drugscan® is one of only a few nationally CAPaccredited and SAMHSA-certified toxicology laboratories. Drugscan® is a leader in clinical and forensic toxicology, medication monitoring, and drug detection laboratory services. Our mission is to keep everyone in the patient care continuum safe and compliant with all regulations; providing clients with advanced technology, accurate results, and superior customer service! Erchonia Corporation Booth #217 www.erchonia.com Erchonia is the global leader in low level laser health care applications. Over the last 16 years Erchonia has researched and developed with the world’s leading physicians to advance the science of lasers. Erchonia lasers are proven through rigorous Level 1 clinical trials to prove their efficacy. Genova Diagnostics Booth #319 www.gdx.net Genova Diagnostics is a leading clinical laboratory applying systems-based testing approaches to the diagnosis, treatment, and prevention of complex chronic disease. Genova specializes in clinical laboratory services with actionable information. Gensco Laboratories, LLC Booth #423 www.genscolabs.com GF Health Products, Inc. Booth # 202 www.Grahamfield.com GF Health Products is proud to feature our Hausted® Stretchers, Surgical and Specialty Chairs, Lumex® Clincial Recliners, and E & J® transport and specialty wheelchairs—products known throughout the world for quality, comfort, and durability.

ITelagen® redefines Healthcare IT for pain management practices by providing PainCare™ for NextGen® EHR, a fully integrated technology, uniquely designed to meet the documentation needs of pain management physicians. Paincare™ is part of a total solution including unlimited onsite & remote technical support for all staff, implementation, and secure hosting of patient data.

Booth #511

Visit the AIPM Info Booth in the Exhibit Hall to learn about: The Pain Care Learning Center • Credentialing The Pain Practitioner • Currents SPPAN • CME/CEU

| T H E PA I N PRACTITION ER | A U G U S T / S E P T E M B E R 2 0 1 6

2 016 M EE T I N G E X H I B I TO R L I S T I N G S

Pain Management Drug Screening with easy, non-invasive collections Oral Fluid Testing

provides an option for detecting recent usage with samples swabbed directly from the mouth

Hair Testing

offers a three-month timeframe for checking longterm lifestyle choices for new or at-risk patients

Visit us at Booth # 323 ● www.omeglabs.net ● 1-800-665-5569

Booth #411

MedTest provides tailored solutions that address the clinical laboratory’s challenges of improving quality, while reducing costs. MedTest Ensembles provide: Consulting, Scalable Instrumentation, Reagents (Chemistry, Hematology, Drugs of Abuse Screening and Confirmation), Installation, Training, Support, and On-Site Service. Its solutions span the continuum from simple to highly complex labs.

www.Medtest.com BOOTH #503

Booth 501

+ 2:11 50 Safety6,000 in Numbers… 24/7 1,300 Learn More about Ours in San Antonio

400+ TM

™

eon Global Health’s mission is to lead a revolution in prevention, diagnosis, and treatment of diseases by providing healthcare providers with clinically actionable information that promotes patient centric, personalized medical care. We offer innovative solutions in the areas of Cancer Genomics, Toxicology, Pharmacogenomics, and Health Technology Applications. To learn more, ask your doctor or visit aeonglobalhealth.com

Patient Safety. First!

Excellence in Standard of Care

USP <797>

www.aispaincare.com

THINK

OUTSIDE THE BOTTLE

ENTER TO WIN an Amazon Fire TV Stick COME SEE US AT BOOTH #512 800.266.6969 | www.vqorthocare.com Amazon and Fire are trademarks of Amazon.com, Inc. or its afﬁliates. Amazon devices are given away on behalf of VQ OrthoCare. Amazon is not a sponsor of this event

A novel device for SPG / PPG/ Trigeminal blocks

SphenoCath® is a registered trademark of Dolor Technologies, LLC

See us at booth # 419 THE PAIN PRACTITIONE R

| VOLUME 26, NUMBER 4 |

2 7 t h a n n u a l M E E T I N G s p e c i a l s e c ti o n

Hemosure, Inc. Booth #306 www.hemosure.com Hemosure is recognized worldwide in immunological fecal occult blood testing, also known as iFOB or FIT testing. Colorectal cancer, when discovered in the early stages, is the most preventable and curable of all cancers. Hemosure is dedicated and focused on educating physicians and patients on this subject. HORIBA Medical Booth #223 www.horiba.com/medical The HORIBA Group of companies provides an array of systems for applications from standard chemistry through to the testing of drugs of abuse within the IVD market. Proven quality and trustworthy performance have established confidence in the HORIBA Brand. The HORIBA Medical division distributes chemistry and hematology systems in the U.S. Infinite Therapeutics Booth #317 www.infinitymassagechairs.com The Infinity Riage features the most advanced 3D massage technology on the market and an L-shaped roller track to deliver unmatched stress relief. Users can also control the chair from their Apple or Android devices with the Infinity Riage app. The 3D Infinity Riage provides the ultimate massage every time. Itelagen Booth #511 www.itelagen.com ITelagen® redefines health care IT for pain management practices by providing PainCare™ for NextGen® EHR, a fully integrated technology, uniquely designed to meet the documentation needs of pain management physicians. Paincare™ is part of a total solution including unlimited onsite and remote technical support for all staff, implementation, and secure hosting of patient data. The Joint Commission Booth #509 www.jointcommission.org Accrediting over 2,100 ambulatory care organizations, The Joint Commission can help you reduce risk and create a culture of excellence that illustrates your commitment to safe, high quality care. Learn how accreditation offers access to proven, customized solutions to improve patient safety. Visit booth #509, call (630) 792-5286, visit www.jointcommission. org/AHC. K-Laser Booth #311 www.K-laser.com Built upon a solid foundation of research and development, K-Laser has earned world-wide recognition for its Class IV Laser Therapy treatments that accelerate wound healing, decrease inflammation, and increase joint flexibility with no known side effects. The K-Laser development team is dedicated to offering the

most advanced technologies, with a neverending dedication to innovation.

trials, and in clinical trials. Console or portable models; anywhere treatment is needed.

LightForce Therapy Lasers by LiteCure Medical Booth #316 www.lightforcelasers.com LightForce Therapy Lasers by LiteCure Medical are the most advanced deep tissue therapy lasers available. Committed to innovation and science, LiteCure Medical is constantly conducting scientific studies and providing educational opportunities. Get your patients back in action with the therapeutic power of LightForce Deep Tissue Therapy Lasers.

Nervomatrix Corp Booth#303 www.nervomatrix.com The Soleve is a novel, computerized, noninvasive back and neck pain treatment medical device. The system is fully automated, first, locating the most painful trigger points and then treating each and every trigger point with dense electrical stimulation for two minutes per point. The entire diagnosis and treatment takes less than 30 minutes and the protocol suggests a series of six treatments per patient.

Linden Care Booth #402 www.lindencare.com Linden Care is committed to providing the highest level of pharmacy services through collaborative relationships with patients, physicians, caregivers, and pharmaceutical manufacturing partners.

Neurogenx Booth #520 www.neurogenx.com

Medical Pillars Diagnostics Booth #505 www.medicalpillars.com Medical Pillars Diagnostics specializes in painspecific biomarkers that provide comprehensive insight and treatment suggestions for integrative and functional pain specialists. With compliant financial models for doctors, Medical Pillars is an all-around solution that helps optimize clinical outcomes and provides a new and lucrative revenue stream for your practice. Medtest Booth #503 www.Medtest.com MedTest provides tailored solutions that address the clinical laboratory’s challenges of improving quality, while reducing costs. MedTest ensembles provide: consulting, scalable instrumentation, reagents (chemistry, hematology, drugs of abuse screening and confirmation), installation, training, support, and on-site service. Its solutions span the continuum from simple to highly complex labs. Micro Distributing Booth #310 www.micro-distributing.com Micro Distributing (MD) is a leading provider of drug and alcohol point-of-care test products and laboratory services. We offer 15 CLIA waived drugs of abuse in test cup and dip card device formats, in addition to certified laboratory partners for a comprehensive solution to all your testing needs. Multi Radiance Medical Booth #205 www.multiradiance.com Multi Radiance manufactures FDA-cleared super pulsed lasers, for drug-free pain relief. Our LaserStim™ allows the practitioner to identify an area and automatically deliver the dose. MR4 Lasers are the only therapeutic lasers validated in-vitro, in-vivo, in laboratory

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Omega Laboratories Booth #323 www.omegalabs.net Omega Laboratories is the industry leader in hair and oral fluid testing for drugs of abuse. Omega offers a variety of panel options, seamless data integration, competitive pricing, superior client service, and the fastest turnaround time in the industry. Omega’s services are used by physicians, clinics, and insurance companies worldwide. Pain Medicine News Booth #422 www.PainMedicineNews.com Pain Medicine News (PMN) is designed to meet the needs of physicians involved in managing pain and is mailed to 45,179 pain-treating physicians. PMN offers extensive coverage of pain-related presentations at major clinical meetings, presents in-depth clinical reviews written by thought leaders, as well as cuttingedge practice management articles. Pernix Therapeutics Booth #300 www.pernixtx.com Pernix Therapeutics is a specialty pharmaceutical business with a focus on acquiring, developing, and commercializing prescription drugs primarily for the U.S. market. Pernix targets underserved therapeutic areas such as CNS, including neurology and pain management, and has an interest in expanding into additional specialty segments. To learn more visit www.pernixtx.com. PharmBlue, LLC Booth #412 www.pharmblue.com PharmBlue is a national specialty pharmacy, providing services to individuals with chronic conditions taking multiple medications, and the clinicians who serve them. PharmBlue has enrolled members throughout the country, filling pharmacy needs with special focus on the needs of HIV/AIDS, hepatitis C, behavioral health, chronic pain, and substance abuse patients.

2 0 1 6 meeti n g E X H I B I T O R L I S T I N G S

Physician Owned Surgery Centers Booth #510 Physician Owned Surgery Centers (POSC) owns and operates multispecialty and profitable ambulatory surgery centers in partnership with physicians. We also acquire centers for the purpose of expanding/restructuring them. Physicians Angels Booth #200 www.physiciansangels.com Physicians Angels is the country’s leading provider of Virtual Medical Scribe services. Our Virtual Scribes provide clinics and hospitals with real-time EHR data management that allows doctors to remain productive and focus on patient care, not on data care. Practical Pain Management Booth #309 www.practicalpainmanagement.com Practical Pain Management (PPM), in its 16th year, is the nation’s premier teaching journal for more than 40,000 pain practitioners. PPM provides the tools, information, and resources to help HCPs treat their chronic pain patients and to navigate the ever-shifting landscape of pain management. PPM articles are authored by leading clinicians from across the country. Precision Diagnostics Booth #203 www.precisiondxlab.com Precision Diagnostics is an innovative specialty medication adherence and substance abuse monitoring company employing industryleading clinical laboratory technology and robotic automation to ensure accuracy. Precision Diagnostics specializes in quantitative confirmation urine drug testing designed to monitor patients on chronic opioid therapy that can help improve patient compliance and help protect your practice. Quest Diagnostics Booth #322 www.questdiagnostics.com Quest Diagnostics empowers people to take action to improve health outcomes. Derived from the world’s largest database of clinical lab results, our diagnostic insights reveal new avenues to identify and treat disease, inspire healthy behaviors, and improve health care management. We serve half of the physicians and hospitals in the United States. Rebel Herbs Booth #302 www.rebelherbs.com The Rebel Herbs brand of herbal products is “not for ordinary mortals.” A full line of powerful formulas, superstar single herb powders, and Herbal Vapors, available only through health care professionals. The Rebel Herbs product line is made exclusively from herbs and spices that come from our certified organic farms.

Sevocity Electronic Health Records Booth #305 www.Sevocity.com Sevocity EHR is a fully functional, customizable EHR that is easy to learn, easy to use, and affordable. Sevocity is designed to respect your time—to help you quickly and accurately document and run your practice or clinic. For more information, visit www.sevocity.com. Si-Bone, Inc. Booth #416 www.si-bone.com SI-BONE, Inc. is the leading sacroiliac (SI) joint medical device company dedicated to the development of tools for diagnosing and treating patients with low back issues related to SI joint disorders. The company is manufacturing and marketing a minimally invasive surgical (MIS) technique for the treatment of SI joint pathology. StreamlineMD Booth #420 www.streamlinemd.com StreamlineMD is a certified provider of electronic health record (EMR), practice management (PM), and billing solutions. The company offers its services principally to independent physician practices focused on pain management and related specialties. The StreamlineMD EHR contains fully developed clinical content for interventional pain management including more than 50 procedures. In addition, StreamlineMD is one of the few EMR products that is EPCS certified, allowing physicians to transmit controlled substances electronically. Surgenex Booth #308 www.surgenex.com Surgenex® is the producer and distributor of the highest quality of amniotic membrane tissue allograft in the industry. Our products are used for a wide variety of clinical applications including pain management and wound care. Surgenex has developed innovative processes and safety protocols, which deliver the highest tissue viability and safety standards. TEVA CNS Booth #401 www.tevausa.com Teva Pharmaceuticals is a leading global pharmaceutical company with a focus in pain care. With a diverse portfolio and pipeline of products to help advance treatments in pain management, Teva is committed to supporting responsible pain care that meets the needs of people living with pain as well as health care professionals. Therapath Neuropathology Booth #518 www.therapath.com Therapath provides specialty neuropathology testing. Diagnostic services include epidermal nerve fiber density testing, sweat gland nerve fiber density testing, muscle biopsy analysis, and peripheral nerve biopsy analysis.

Thorne Research, Inc. Booth #515 www.thorne.com Thorne Research sets the standard for manufacturing quality nutritional supplements available through health care practitioners. In addition to foundational supplements, Thorne Research offers products to address nutritional deficiencies in cancer patients and those with cardiovascular disease, for support of pain management, a product line for athletes, and related practice management programs. US Pain Foundation Booth #210 www.uspainfoundation.org U.S. Pain Foundation is a 501(c) 3 non-profit organization dedicated to serving those who live with pain conditions and their care providers. Our mission is to educate, connect, inform, and empower those living with pain while also advocating on behalf of the entire pain community. The Valletta Group Booth #320 www.thevallettagroup.com The Valletta Group has provided superior physician billing results since 2004. The Valletta Group provides fully transparent data, relevant reporting, meticulous follow-up of insurance claims, and a highly redundant process of accurately completing transactions to minimize errors, maximize revenues, and provide a clear picture of a practice’s financial health. Vitamix Booth #312 www.vitamix.com Improving the vitality of people’s lives and liberating the world from conventional food and beverage preparation boundaries. VQ OrthoCare Booth #512 www.vqorthocare.com Founded in 1989, based in Irvine, California, VQ OrthoCare, a leading provider of noninvasive medical solutions focused on bone, joint, and soft-tissue conditions. Including in-home patient fitting of braces and medical devices, physician and patient support; with brand names such as BioniCare®, Avid™ IF 2, OActive® 2, Catalyst-Propel™OA, Catalyst-Elite™ and Catalyst-Propel™. Wolters Kluwer Booth #201 www.wolterskluwer.com Wolters Kluwer is a leading publisher of medical, health, and science publications. We offer an extensive selection of medical books, journals, and electronic media for doctors, nurses, specialized clinicians, and students. Please visit booth 201 to browse our comprehensive product line.

THE PAIN PRACTITIONE R

| VOLUME 26, NUMBER 4 |

For patients who need consistent analgesia plus tolerability, now you can help them

Experience living on film A different way to transition from short-acting to long-acting opioid therapy BELBUCA™ is the first and only Schedule III long-acting opioid that uses novel buccal film technology to deliver buprenorphine for appropriate patients living with chronic pain1*

About BELBUCA™ *BELBUCA™ (buprenorphine) buccal film is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Limitations of Use • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with long-acting opioid formulations, reserve BELBUCA™ for use in patients for whom alternative treatment options (eg, non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. • BELBUCA™ is not indicated as an as-needed (prn) analgesic.

IMPORTANT SAFETY INFORMATION about BELBUCA™ WARNING: ADDICTION, ABUSE, and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; and NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse BELBUCA™ exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing BELBUCA™, and monitor patients regularly for the development of these behaviors or conditions. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of BELBUCA™. Monitor for respiratory depression, especially during initiation of BELBUCA™ or following a dose increase. Misuse or abuse of BELBUCA™ by chewing, swallowing, snorting, or injecting buprenorphine

CONTRAINDICATIONS BELBUCA™ is contraindicated in patients with: • Significant respiratory depression • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment • Known or suspected gastrointestinal obstruction, including paralytic ileus • Hypersensitivity (eg, anaphylaxis) to buprenorphine

extracted from the buccal film will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death. Accidental Exposure Accidental exposure to even one dose of BELBUCA™, especially by children, can result in a fatal overdose of buprenorphine. Neonatal Opioid Withdrawal Syndrome Prolonged use of BELBUCA™ during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse • BELBUCA™ contains buprenorphine, a Schedule III controlled substance. As an opioid, BELBUCA™ exposes users to the risks of addiction, abuse, and misuse.

Reference: 1. BELBUCA™ (Prescribing Information). Malvern, PA: Endo Pharmaceuticals Inc; December 2015.

Find out how to transition appropriate patients onto long-acting BELBUCA™ at BELBUCAfilm.com

A different path forward • Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing BELBUCA™, and monitor all patients receiving BELBUCA™ for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed BELBUCA™, but use in such patients necessitates intensive counseling about the risks and proper use of BELBUCA™, along with intensive monitoring for signs of addiction, abuse, or misuse. • Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed BELBUCA™ and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused. • Abuse or misuse of BELBUCA™ by swallowing may cause choking, overdose, and death. • Opioid agonists such as BELBUCA™ are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Strategies to reduce the risk include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug. • Contact a local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Life-Threatening Respiratory Depression • Serious, life-threatening, or fatal respiratory depression has been reported with the use of buprenorphine, even when used as recommended. Respiratory depression, from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status. • While serious, life-threatening or fatal respiratory depression can occur at any time during the use of BELBUCA™, the risk is greatest during initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with BELBUCA™ and following dose increases. • To reduce the risk of respiratory depression, proper dosing and titration of BELBUCA™ are essential. Overestimating the dose of BELBUCA™ when converting patients from another opioid product may result in fatal overdose with the first dose. • Accidental exposure to BELBUCA™, especially in children, can result in respiratory depression and death due to an overdose of buprenorphine ADVERSE REACTIONS • The most common adverse reactions (≥5%) reported by patients treated with BELBUCA™ in the clinical trials were nausea, constipation, headache, vomiting, fatigue, dizziness, somnolence, diarrhea, dry mouth, and upper respiratory tract infection.

Please see Brief Summary of full Prescribing Information on accompanying pages. Please see additional Important Safety Information and full Prescribing Information at BELBUCA.com/physician. Rx Only BELBUCA™ is trademark of Endo International plc or one of its affiliates. © 2016 Endo Pharmaceuticals Inc. All rights reserved. Malvern, PA 19355 BL-04375/March 2016 BELBUCA.com 1-800-462-ENDO (3636)

BRIEF SUMMARY OF PRESCRIBING INFORMATION

For complete details please see the full Prescribing Information and Medication Guide.

WARNING: ADDICTION, ABUSE, and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; and NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse BELBUCA™ exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing BELBUCA™, and monitor patients regularly for the development of these behaviors or conditions. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of BELBUCA™. Monitor for respiratory depression, especially during initiation of BELBUCA™ or following a dose increase. Misuse or abuse of BELBUCA™ by chewing, swallowing, snorting, or injecting buprenorphine extracted from the buccal film will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death. Accidental Exposure Accidental exposure to even one dose of BELBUCA™, especially by children, can result in a fatal overdose of buprenorphine. Neonatal Opioid Withdrawal Syndrome Prolonged use of BELBUCA™ during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. 1 INDICATIONS AND USAGE BELBUCA™ is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Limitations of Use • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with long-acting opioid formulations, reserve BELBUCA™ for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release options) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. • BELBUCA™ is not indicated as an as-needed (prn) analgesic. 4 CONTRAINDICATIONS BELBUCA™ is contradicted in patients with: • Significant respiratory depression [see Warnings and Precautions (5.2)] • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.6)] • Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.13)] • Hypersensitivity (e.g., anaphylaxis) to buprenorphine [see Warnings and Precautions (5.12), and Adverse Reactions (6)] 5 WARNINGS AND PRECAUTIONS 5.1 Addiction, Abuse, and Misuse BELBUCA™ contains buprenorphine, a Schedule III controlled substance. As an opioid, BELBUCA™ exposes users to the risks of addiction, abuse, and misuse. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing BELBUCA™ and monitor all patients receiving BELBUCA™ for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed BELBUCA™, but use in such patients necessitates intensive counseling about the risks and proper use of BELBUCA™, along with intensive monitoring for signs of addiction, abuse, or misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed BELBUCA™. Addiction can occur at recommended dosages and if the drug is misused or abused [see Drug Abuse and Dependence (9)]. Abuse or misuse of BELBUCA™ by swallowing may cause choking, overdose, and death [see Overdosage (10)]. Opioid agonists such as buprenorphine are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing BELBUCA™. Strategies to reduce the risk include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 5.2 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of buprenorphine, even when used as recommended. Respiratory depression, from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening or fatal respiratory depression can occur at any time during the use of BELBUCA™, the risk is greatest during initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with BELBUCA™ and following dose increases. To reduce the risk of respiratory depression, proper dosing and titration of BELBUCA™ are essential [see Dosage and Administration (2.3)]. Overestimating the dose of BELBUCA™ when converting patients from another opioid product may result in fatal overdose with the first dose. Accidental exposure to BELBUCA™, especially in children, might result in respiratory depression and death due to an overdose of buprenorphine. 5.3 Neonatal Opioid Withdrawal Syndrome Prolonged use of BELBUCA™ during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, failure to gain weight; and there have been reports of convulsions, apnea, respiratory depression, and bradycardia. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn [see Use in Specific Populations (8.1)]. 5.4 Risks due to Interactions with Central Nervous System Depressants Hypotension, profound sedation, coma or respiratory depression may result if BELBUCA™ is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of BELBUCA™ in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of alcohol or illicit drugs that cause CNS depression. If the decision to begin BELBUCA™ is made, start with a lower dosage of BELBUCA™, monitor patients for signs of sedation, respiratory depression, and hypotension, and consider using a lower dosage of the concomitant CNS depressant [see Drug Interactions (7)]. 5.5 Risk of Life-Threatening Respiratory Depression in Elderly, Cachectic, and Debilitated Patients Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Monitor such patients closely, particularly when initiating and titrating BELBUCA™ and when BELBUCA™ is given concomitantly with other drugs that depress respiration [see Warnings and Precautions (5.2)]. 5.6 Risk of Apnea in Patients with Chronic Pulmonary Disease The use of BELBUCA™ in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated. BELBUCA™-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive, including apnea, even at recommended dosages of BELBUCA™ [see Warnings and Precautions (5.2)]. Therefore, closely monitor these patients, especially when initiating and titrating BELBUCA™. Alternatively, consider the use of alternative non-opioid analgesics in these patients. 5.7 QTc Prolongation BELBUCA™ has been observed to prolong the QTc interval in some subjects participating in clinical trials. Consider these observations in clinical decisions when prescribing BELBUCA™ to patients with hypokalemia, hypomagnesemia, or clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia. Periodic electrocardiographic (ECG) monitoring is recommended in these patients. Avoid the use of BELBUCA™ in patients with a history of Long QT Syndrome or an immediate family member with this condition or those taking Class IA antiarrhythmic medications (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, dofetilide), or other medications that prolong the QT interval [see Dosage and Administration (2.3), Adverse Reactions (6.1), and Clinical Pharmacology (12.2)].

5.8 Severe Hypotension BELBUCA™ may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions (7)]. Monitor these patients for signs of hypotension after initiating or titrating the dose of BELBUCA™. In patients with circulatory shock, BELBUCA™ may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of BELBUCA™ in patients with circulatory shock. 5.9 Risks of Use in Patients with Head Injury or Increased Intracranial Pressure In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), BELBUCA™ may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with BELBUCA™. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of BELBUCA™ in patients with impaired consciousness or coma. 5.10 Hepatotoxicity Cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving sublingual formulations of buprenorphine for the treatment of opioid dependence, both in clinical trials and in post-marketing adverse events reports. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy. In many cases, the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant usage of other potentially hepatotoxic drugs, and ongoing injection drug abuse may have played a causative or contributory role. For patients at increased risk of hepatoxicity (e.g., patients with a history of excessive alcohol intake, intravenous drug abuse or liver disease), obtain baseline liver enzyme levels and monitor periodically during treatment with BELBUCA™. 5.11 Risk of Overdose in Patients With Moderate to Severe Hepatic Impairment In a pharmacokinetic study in subjects dosed with buprenorphine sublingual tablets, buprenorphine plasma levels were found to be higher and the half-life was found to be longer in subjects with moderate and severe hepatic impairment, but not in subjects with mild hepatic impairment. For patients with severe hepatic impairment, a dose adjustment is recommended, and patients with moderate or severe hepatic impairment should be monitored for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine [see Dosage and Administration (2.5), Use in Specific Populations (8.6)]. 5.12 Anaphylactic/Allergic Reactions Cases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in post-marketing experience. The most common signs and symptoms include rashes, hives, and pruritus. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. BELBUCA™ is contraindicated in patients with a history of hypersensitivity to buprenorphine. 5.13 Risk of Use in Patients with Gastrointestinal Conditions BELBUCA™ is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. BELBUCA™ may cause spasm of the sphincter of Oddi. Opioids may cause increases in the serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. 5.14 Increased Risk of Seizures in Patients with Seizure Disorders Buprenorphine may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during BELBUCA™ therapy. 5.15 Risks of Use in Cancer Patients with Oral Mucositis Cancer patients with oral mucositis may absorb buprenorphine more rapidly than intended and are likely to experience higher plasma levels of the opioid. For patients with known or suspected mucositis, a dose reduction is recommended. Monitor these patients carefully for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)]. 5.16 Risks of Driving and Operating Machinery BELBUCA™ may impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to side effects of BELBUCA™ and know how they will react to the medication. 6 ADVERSE REACTIONS The following serious adverse reactions described elsewhere in the labeling include: • Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] • Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3)] • Interactions with other CNS Depressants [see Warnings and Precautions (5.4)] • QTc Prolongation [see Warnings and Precautions (5.7)] • Severe Hypotension [see Warnings and Precautions (5.8)] • Anaphylactic/Allergic Reactions [see Warnings and Precautions (5.12)] • Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.13)] • Seizures [see Warnings and Precautions (5.14)] 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 2,127 patients were treated with BELBUCA™ in controlled and open-label chronic pain trials. There were 504 patients treated for approximately six months and 253 patients treated for approximately one year. The clinical trial population consisted of patients with chronic moderate-to-severe pain. The most common serious adverse drug reactions (all ≤ 0.2%) occurring during clinical trials with BELBUCA™ were: cellulitis, pneumonia, ileus, atrial fibrillation, coronary artery disease, cerebrovascular accident, syncope, transient ischemic attack, chest pain, non-cardiac chest pain, ankle fracture, cholecystitis, osteoarthritis, and dehydration. The most common adverse events (≥ 2%) leading to discontinuation were nausea, vomiting, and liver function test abnormality. The most common adverse events (≥ 5%) reported by opioid naïve, opioid experienced, and overall patients exposed to BELBUCA™ in clinical trials and compared against placebo are shown in Tables 2, 3 and 4: Table 2: Adverse Events Reported in ≥5% of Patients during the Open-Label Titration Phase and Double-Blind Treatment Phase of Controlled Studies: Opioid-Naïve Patients Open-Label Titration Phase

Double-Blind Treatment Phase

BELBUCA™ (N=749)

BELBUCA™ (N=229)

Placebo (N=232)

Nausea

50%

10%

Constipation

13%

Vomiting

<1%

MedDRA Preferred Term

Headache

Dizziness

<1%

Somnolence

<1%

Fatigue

Table 3: Adverse Events Reported in ≥5% of Patients during the Open-Label Titration Phase and Double-Blind Treatment Phase of Controlled Studies: Opioid-Experienced Patients Open-Label Titration Phase BELBUCA (N=810)

BELBUCA (N=254)

Placebo (N=256)

17%

Constipation

Vomiting

Headache

Dizziness

<1%

Somnolence

<1%

Drug Withdrawal Syndrome

10%

™

Table 4: Adverse Events Reported in ≥5% of Patients during the Open-Label Titration Phase and Double-Blind Treatment Phase of Controlled Studies Open-Label Titration Phase MedDRA Preferred Term

Double-Blind Treatment Phase

™

BELBUCA (N=1889)

BELBUCA (N=600) ™

Placebo (N=606)

If concomitant use is necessary, consider increasing the BELBUCA™ dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider BELBUCA™ dosage reduction and monitor for signs of respiratory depression.

Double-Blind Treatment Phase

Nausea

MedDRA Preferred Term

™

Intervention:

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact:

May reduce the analgesic effect of BELBUCA™ and/or precipitate withdrawal symptoms.

Intervention:

Avoid concomitant use.

Examples:

butorphanol, nalbuphine, pentazocine

Muscle Relaxants Clinical Impact:

Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

Intervention:

Monitor patients receiving muscle relaxants and BELBUCA™ for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of BELBUCA™ and/or the muscle relaxant as necessary.

Diuretics Clinical Impact:

Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.

Intervention:

Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Nausea

33%

Anticholinergic Drugs

Constipation

11%

Clinical Impact:

The concomitant use of opioid analgesics, including buprenorphine, and anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

Vomiting

Intervention:

Headache

Monitor patients for signs of urinary retention or reduced gastric motility when BELBUCA™ is used concomitantly with anticholinergic drugs.

Dizziness

<1%

Antiretrovirals: Nucleoside reverse transcriptase inhibitors (NRTIs)

Somnolence

<1%

Clinical Impact:

Nucleoside reverse transcriptase inhibitors (NRTIs) do not appear to induce or inhibit the P450 enzyme pathway, thus no interactions with buprenorphine are expected.

Drug Withdrawal Syndrome

Intervention:

None

The most common (≥ 5%), common (≥ 1% to < 5%), and least common (< 1%) adverse reactions reported by patients taking BELBUCA™ in the controlled and open-label clinical studies are presented below: Most common adverse reactions (≥ 5%): nausea, constipation, headache, vomiting, fatigue, dizziness, somnolence, diarrhea, dry mouth, and upper respiratory tract infection. Common (≥ 1% to < 5%) adverse reactions (organized by MedDRA [Medical Dictionary for Regulatory Activities] System Organ Class): Blood and lymphatic system disorders: anemia Gastrointestinal disorders: abdominal pain General disorders and administration site conditions: peripheral edema, pyrexia, drug withdrawal syndrome Infections and infestations: urinary tract infection, nasopharyngitis, sinusitis, bronchitis, gastroenteritis Injury, poisoning, and procedural complications: contusion, fall Metabolism and nutrition disorders: decreased appetite Musculoskeletal and connective tissue disorders: muscle spasms, back pain Psychiatric disorders: anxiety, insomnia, depression Respiratory, thoracic and mediastinal disorders: oropharyngeal pain, sinus congestion Skin and subcutaneous tissue disorders: hyperhidrosis, pruritus, rash Vascular disorders: hot flush, hypertension Least common (<1%) adverse reactions: Abdominal discomfort, acute sinusitis, dyspepsia, toothache, asthenia, chills, cellulitis, tooth abscess, excoriation, laceration, aspartate aminotransferase increased, blood pressure increased, blood testosterone decreased, electrocardiogram QT prolonged, liver function test abnormal, musculoskeletal pain, neck pain, hypoesthesia, lethargy, migraine, tremor, cough, dyspnea, nasal congestion, rhinorrhea 7 DRUG INTERACTIONS Table 5 includes clinically significant drug interactions with BELBUCA™. Benzodiazepines Clinical Impact:

There have been a number of reports regarding coma and death associated with the misuse and abuse of the combination of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection of crushed buprenorphine tablets. Preclinical studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists.

Intervention:

Closely monitor patients with concurrent use of BELBUCA™ and benzodiazepines. Warn patients that it is extremely dangerous to self-administer benzodiazepines while taking BELBUCA™, and warn patients to use benzodiazepines concurrently with BELBUCA™ only as directed by their physician.

Central Nervous System (CNS) Depressants Clinical Impact:

Due to additive pharmacologic effects, the concomitant use of CNS depressants can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.

Intervention:

Consider dose reduction of one or both drugs. Monitor patients for signs of respiratory depression, sedation, and hypotension [see Warnings and Precautions (5.4)].

Examples:

Alcohol, anxiolytics, general anesthetics, hypnotics, neuroleptics, phenothiazines, sedatives, tranquilizers, other opioids.

Inhibitors of CYP3A4 Clinical Impact:

The concomitant use of buprenorphine and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of BELBUCA™ is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the buprenorphine plasma concentration will decrease [see Clinical Pharmacology (12.3)], potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to buprenorphine.

Intervention:

If concomitant use is necessary, consider dosage reduction of BELBUCA™ until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the BELBUCA™ dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

CYP3A4 Inducers Clinical Impact:

The concomitant use of buprenorphine and CYP3A4 inducers can decrease the plasma concentration of buprenorphine [see Clinical Pharmacology (12.3)], potentially resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the buprenorphine plasma concentration will increase [see Clinical Pharmacology (12.3)], which could increase or prolong both therapeutic effects and adverse reactions and may cause serious respiratory depression.

Antiretrovirals: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Clinical Impact:

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized principally by CYP3A4. Efavirenz, nevirapine, and etravirine are known CYP3A inducers, whereas delaviridine is a CYP3A inhibitor. Significant pharmacokinetic interactions between NNRTIs (e.g., efavirenz and delavirdine) and buprenorphine have been shown in clinical studies, but these pharmacokinetic interactions did not result in any significant pharmacodynamic effects.

Intervention:

Patients who are on chronic BELBUCA™ treatment should have their dose monitored if NNRTIs are added to their treatment regimen.

Examples:

efavirenz, nevirapine, etravirine, delavirdine

Antiretrovirals: Protease inhibitors (PIs) Clinical Impact:

Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects. Other PIs with CYP3A4 inhibitory activity (atazanavir and atazanavir/ritonavir) resulted in elevated levels of buprenorphine and norbuprenorphine, and patients in one study reported increased sedation. Symptoms of opioid excess have been found in postmarketing reports of patients receiving buprenorphine and atazanavir with and without ritonavir concomitantly.

Intervention:

Monitor patients taking BELBUCA™ and atazanavir with and without ritonavir, and dose reduction of BELBUCA™ may be warranted.

Examples:

atazanavir, ritonavir

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of BELBUCA™ or buprenorphine in pregnant women. Limited published data on use of buprenorphine, the active ingredient in BELBUCA™, in pregnancy, have not shown an increased risk of major malformations. In animal reproduction studies, embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis via the oral route of administration at doses approximately 53 to 11 times the maximum recommended human dose (MRHD), respectively. In pre- and post-natal development studies in rats, dystocia was observed after treatment with buprenorphine via the IM route of administration at a dose approximately 27 times the MRHD, and increased neonatal death was observed after treatment via the oral, IM, and SC routes of administration at doses approximately 4, 3, and 0.5 times the MRHD, respectively. No teratogenic effects were observed in rats treated with buprenorphine via the oral, IM, and IV routes of administration during organogenesis at doses approximately 853, 27, and 4 times the MRHD, respectively, or in rabbits treated with buprenorphine via the oral, SC, and IV routes of administration at doses approximately 267, 53, and 9 times the MRHD, respectively. However, in a few studies, some events such as acephalus, omphalocele, and skeletal abnormalities were observed but these findings were not clearly treatment-related [see Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Observe newborns for symptoms of neonatal opioid withdrawal syndrome, including poor feeding, diarrhea, irritability, tremor, rigidity, and seizures, and manage accordingly [see Warnings and Precautions (5.3)]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist such as naloxone must be available for reversal of opioid-induced respiratory depression in the neonate. BELBUCA™ is not recommended for use in women immediately prior to labor, when shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including BELBUCA™, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Data Animal Data Buprenorphine administration during organogenesis was not teratogenic in rats or rabbits after intramuscular (IM) or subcutaneous (SC) doses up to 5 mg/kg/day (estimated exposure was approximately 27 and 53 times, respectively, the maximum recommended human dose (MRHD) for buccal BELBUCA™ of 1.8 mg on a mg/m2 basis), after IV doses up to 0.8 mg/kg/day (estimated exposure was approximately 4 and 9 times, respectively, the MRHD), or after oral doses up to 160 mg/kg/day in rats (estimated exposure was approximately 853 times the MRHD) and 25 mg/kg/day in rabbits (estimated exposure was approximately 267 times the MRHD). Significant increases in skeletal abnormalities (e.g., extra thoracic vertebra or thoraco-lumbar ribs) were noted in rats after SC administration of 1 mg/kg/day and up (estimated exposure was approximately 5 times the MRHD), but were not observed at oral doses up to 160 mg/kg/day (estimated exposure was approximately 853 times the MRHD. Increases in skeletal abnormalities in rabbits after IM administration of 5 mg/kg/day (estimated exposure was approximately 53 times the MRHD) or oral administration of 1 mg/kg/day or greater estimated exposure was approximately 11 times the MRHD) were not statistically significant. In rabbits, buprenorphine produced statistically significant pre-implantation losses at oral doses of 1 mg/kg/day or greater (estimated exposure was approximately 11 times the MRHD) and post-implantation losses that were statistically significant at IV doses of 0.2 mg/kg/day or greater (estimated exposure was approximately 2 times the MRHD). Dystocia was noted in pregnant rats treated intramuscularly with buprenorphine 5 mg/kg/day (approximately 27 times the MRHD). Fertility, peri- and post-natal development studies with buprenorphine in rats indicated increases in neonatal mortality after oral doses of 0.8 mg/kg/day and up (approximately 4 times the MRHD), after IM doses of 0.5 mg/kg/day and up (approximately 3 times the MRHD), and after SC doses of 0.1 mg/kg/day and up (approximately 0.5 times the MRHD). Delays in the occurrence of righting reflex and startle response were noted in rat pups at an oral dose of 80 mg/kg/day (approximately 427 times the MRHD).

8.2 Lactation Risk Summary Based on two studies in 13 lactating women being treated for opioid dependence and their breastfed infants, buprenorphine and its metabolite norbuprenorphine are present in low levels in human milk and infant urine, and available data have not shown adverse reactions in breastfed infants [see Data]. There are no data on the effects of BELBUCA™ on milk production. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with BELBUCA™. Clinical Considerations Infants exposed to BELBUCA™ through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of buprenorphine is stopped or when breast-feeding is stopped. Data Based on limited data from a study of six lactating women being treated for opioid dependence who were taking a median oral dose of buprenorphine of 0.29 mg/kg/day 5-8 days after delivery, breast milk contained a median infant dose of 0.42 mcg/kg/day of buprenorphine and 0.33 mcg/kg/day of norbuprenorphine, which are equal to 0.2% and 0.12% of the maternal weight-adjusted dose. The median concentrations of buprenorphine and norbuprenorphine in infant urine were 1.0 nmol/L and 2.3 nmol/L, respectively. Based on limited data from a study of seven lactating women being treated for opioid dependence who were taking a median oral dose of buprenorphine of 7 mg/day an average of 1.12 months after delivery, the mean milk concentrations of buprenorphine and norbuprenorphine were 3.65 mcg/L and 1.94 mcg/L, respectively. Based on the limited data from this study, and assuming milk consumption of 150 mL/kg/day, an exclusively breastfed infant would receive an estimated mean of 0.55 mcg/kg/day of buprenorphine and 0.29 mcg/kg/day of norbuprenorphine, which are 0.38% and 0.18% of the maternal weight-adjusted dose. No adverse reactions were observed in the infants in these two studies. 8.4 Pediatric Use The safety and efficacy of BELBUCA™ have not been established in pediatric patients. 8.5 Geriatric Use Of the total number of patients that were treated with BELBUCA™ in controlled and open-label chronic pain trials (2,127), 340 patients were 65 years and older. Of those, 49 patients were aged 75 years and older. The incidences of selected BELBUCA™-related adverse effects were higher in older subjects. No notable differences in pharmacokinetics were observed from population pharmacokinetic analysis in subjects aged 65 compared to younger subjects. Other reported clinical experience with buprenorphine has not identified differences in responses between the elderly and younger patients. Although specific dose adjustments on the basis of advanced age are not required for pharmacokinetic reasons, use caution in the elderly population to ensure safe use [see Clinical Pharmacology (12.3)]. 8.6 Hepatic Impairment BELBUCA™ has not been evaluated in patients with severe hepatic impairment. The effects of hepatic impairment on the pharmacokinetics of buprenorphine were evaluated in a pharmacokinetic study. Buprenorphine is extensively metabolized in the liver and buprenorphine plasma levels were found to be higher and the half-life was found to be longer in subjects with moderate and severe hepatic impairment, but not in subjects with mild hepatic impairment. Given that increased buprenorphine plasma levels are associated with a greater risk of toxicity and overdose, a dosage reduction in patients with severe hepatic impairment (i.e., Child-Pugh C) is recommended [see Dosage and Administration (2.5)]. Monitor patients with severe hepatic impairment for signs and symptoms of overdose. A dosage reduction in patients with moderate hepatic impairment (Child-Pugh B) is not needed, however, monitor these patients for signs and symptoms of toxicity or overdose. A dosage reduction in patients with mild hepatic impairment (Child-Pugh A) is not needed [see Dosage and Administration (2.5), Warnings and Precautions (5.11) and Clinical Pharmacology (12.3)]. 8.7 Renal Impairment No differences in buprenorphine pharmacokinetics were observed between 9 dialysis-dependent patients and 6 patients with normal renal function following IV administration of 0.3 mg buprenorphine. 9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance BELBUCA™ contains buprenorphine hydrochloride, a Schedule III controlled substance with an abuse potential similar to other Schedule III opioids. BELBUCA™ can be abused and is subject to misuse, abuse, addiction, and criminal diversion [see Warnings and Precautions (5.1)]. 9.2 Abuse All patients treated with opioids, including BELBUCA™, require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carry the risk of addiction, even under appropriate medical use. Prescription drug abuse is the intentional, non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating health care providers(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all persons with substance use disorders. In addition, abuse of opioids can occur in the absence of true addiction. BELBUCA™, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to reduce abuse of opioid drugs. Risks Specific to Abuse of BELBUCA™ BELBUCA™ is intended for buccal use only. Abuse of BELBUCA™ poses a risk of overdose and death. This risk is increased with concurrent abuse of BELBUCA™ with alcohol and other substances, including other opioids and benzodiazepines [see Warnings and Precautions (5.4), Drug Interactions (7)]. Intentional compromise of the buccal film might result in the uncontrolled delivery of buprenorphine and pose a significant risk to the abuser that could result in overdose and death [see Warnings and Precautions (5.1)]. Abuse may occur by applying the buccal film in the absence of legitimate purpose, or by swallowing, snorting, or injecting buprenorphine extracted from the buccal film. 9.3 Dependence Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs and may develop at different rates for different effects. Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, or mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. BELBUCA™ should not be abruptly discontinued [see Dosage and Administration (2.4)]. If BELBUCA™ is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, or diarrhea or increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1)]. 10 OVERDOSAGE Clinical Presentation Acute overdosage with BELBUCA™ is manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations.

Treatment of Overdose In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema, as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques. Naloxone may not be effective in reversing any respiratory depression produced by buprenorphine. High doses of naloxone, 10-35 mg/70 kg, may be of limited value in the management of buprenorphine overdose. The onset of naloxone effect may be delayed by 30 minutes or more. Doxapram hydrochloride (a respiratory stimulant) has also been used. Because the duration of reversal would be expected to be less than the duration of action of buprenorphine from BELBUCA™, carefully monitor the patient until spontaneous respiration is reliably re-established. Even in the face of improvement, continued medical monitoring is required for at least 24 hours because of the possibility of extended effects of buprenorphine. In an individual physically dependent on opioids, administration of an opioid receptor antagonist may precipitate an acute withdrawal. The severity of the withdrawal produced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient with an opioid antagonist, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist. 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide) Addiction, Abuse, and Misuse Inform patients that the use of BELBUCA™, even when taken as recommended, can result in addiction, abuse, and misuse, which could lead to overdose and death [see Warnings and Precautions (5.1)]. Instruct patients not to share BELBUCA™ with others and to take steps to protect BELBUCA™ from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting BELBUCA™ or when the dose is increased and that it can occur even at recommended doses [see Warnings and Precautions (5.2)]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop. Accidental Exposure Inform patients that accidental exposure, especially in children, may result in respiratory depression or death [see Warnings and Precautions (5.2)]. Instruct patients to take steps to store BELBUCA™ securely and to dispose of unused BELBUCA™ by opening unused packages and flushing the film down the toilet. Interaction with Alcohol and other CNS Depressants Inform patients that potentially serious additive effects may occur if BELBUCA™ is used with alcohol or other CNS depressants and not to use such drugs unless supervised by a health care provider [see Warnings and Precautions (5.4)]. Interaction with Benzodiazepines Warn patients that it is extremely dangerous to self-administer benzodiazepines while taking BELBUCA™, and warn patients to use benzodiazepines concurrently with BELBUCA™ only as directed by their physician [see Drug Interactions (7)]. Hypotension Inform patients that BELBUCA™ may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [see Warnings and Precautions (5.12)]. Constipation Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Warnings and Precautions (5.13)]. Driving or Operating Heavy Machinery Inform patients that BELBUCA™ may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see Warnings and Precautions (5.16)]. Anaphylaxis Inform patients that anaphylaxis has been reported with ingredients contained in BELBUCA™. Advise patients how to recognize such a reaction and when to seek medical attention [see Warnings and Precautions (5.12)]. Pregnancy Neonatal Opioid Withdrawal Syndrome Inform female patients of reproductive potential that prolonged use of BELBUCA™ during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see Warnings and Precautions (5.3), Use in Specific Populations (8.1)]. Embryofetal Toxicity Advise female patients that BELBUCA™ can cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)]. Lactation Advise patients that breastfeeding is not recommended during treatment with BELBUCA™ [see Use in Specific Populations (8.2)]. Important Administration Instructions Instruct patients how to properly use BELBUCA™, including the following: 1. To carefully follow instructions for the application of BELBUCA™ and to avoid eating or drinking until it dissolves. 2. To apply BELBUCA™ once daily, or every twelve (12) hours at the same time or times each day. 3. To avoid applying BELBUCA™ to areas of the mouth with any open sores or lesions. 4. To not use BELBUCA™ if the pouch seal is broken or the buccal film is cut, damaged, or changed in any way. Disposal Instruct patients to dispose of BELBUCA™ as soon as it is no longer needed. To dispose of unused BELBUCA™ film, inform the patient to: 1. Remove all BELBUCA™ films from their foil packages. 2. Drop the BELBUCA™ films into toilet and flush. 3. Discard foil packaging in trash. Instruct patients not to flush BELBUCA™ down the toilet in the foil packages or cartons [see Dosage and Administration (2.8)]. Healthcare professionals can telephone Endo Pharmaceuticals (1-800-462-3636) for information on this product.

Distributed by: Endo Pharmaceuticals Inc. Malvern, PA 19355 © 2016 Endo Pharmaceuticals Inc. All rights reserved. This brief summary is based on BELBUCA™ Prescribing Information, Revised 12/2015. BL-04375/March 2016

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