The Pain Practitioner - The Deeper Root of Pain

Integrative Pain Management for Optimal Patient Care

The Pain Practitioner October / November 2016

Can we look deeper to the root of pain?

What’s Missing from this Puzzle?

Heart Rate Variability, Chronic Pain, and Rehabilitating the Autonomic Nervous System Pain Management Groups: Remedy by the Dozens 2016 Annual Meeting Posters

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%

7%

Constipation

13%

4%

3%

Vomiting

8%

4%

<1%

MedDRA Preferred Term

Headache

8%

2%

3%

Dizziness

6%

2%

<1%

Somnolence

7%

1%

<1%

Fatigue

5%

0%

1%

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%

7%

7%

Constipation

8%

3%

1%

Vomiting

7%

5%

2%

Headache

7%

2%

3%

Dizziness

5%

2%

<1%

Somnolence

5%

1%

<1%

Drug Withdrawal Syndrome

0%

4%

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

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.

™

BELBUCA (N=1889)

BELBUCA (N=600)

Placebo (N=606)

Nausea

33%

9%

8%

Anticholinergic Drugs

Constipation

11%

4%

2%

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

7%

5%

2%

Intervention:

Headache

8%

4%

3%

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

Dizziness

6%

2%

<1%

Antiretrovirals: Nucleoside reverse transcriptase inhibitors (NRTIs)

Somnolence

6%

<1%

<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

1%

2%

5%

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

Academy of Integrative Pain Management

The Pain Practitioner OCTOBER/NOVEMBER 2016

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

9

NOTES FROM THE FIELD What’s Missing from this Puzzle?

By Bob Twillman, PhD, FAPM, Executive Director

10 MEMBERSHIP Shared Interest Groups Gather, Grow at Annual Meeting 11 ANNUALMEETING The 27th Annual Meeting: Sweet Validation for Business as Usual

By Christine Rhodes, MS PAGE 11

14 ADVOCACY The Power of a Network

By Amy Goldstein, MSW, Director of the State Pain Policy Advocacy Network 15 PROFESSIONAL DEVELOPMENT Satisfy State CME Requirements in our Pain Care Learning Center

By Debra Nelson-Hogan, Director of Professional Development 16 RESEARCH Research Recap

PAGE 14

21 Heart Rate Variability, Chronic Pain, and Rehabilitating the Autonomic Nervous System

By Raouf Gharbo, DO, and J.P. Ginsberg, PhD 27 Pain Management Groups: Remedy by the Dozens

By Karen Spurgeon Welch, MD, ABFM 31 Annual Meeting Blue Ribbon Posters

PAGE 21

www.aapainmanage.org

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 George D. Comerci, Jr, MD, FACP John Garzione, DPT Christian D. González, MD Michael Kurisu, DO, ABIHM Joseph Matthews, DDS, MSc Liaison to the Board Maggie Buckley

ACADEMY STAFF Executive Director Robert Twillman, PhD, FAPM Director of Professional Development Debra Nelson-Hogan 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 PAGE 27

And More, on the Web...

NOW AVAILABLE ONLINE! Advanced Credentialed Pain Practitioner

Curriculum Review Course Consisting of 15 courses, this 14-hour CME activity can now be taken anytime, anywhere through our online Pain Care Learning Center. https://goo.gl/vnAXvt EXPECTATION MANAGEMENT The Most Challenging Issue in Pain Management

How Christina Lewis, RN-BC, Civil Servant DOD Nurse Case Manager at Tripler Army Medical Center, approaches care for chronic pain patients who just want their pain “cured.” https://goo.gl/G5qg2Fj 2017 ANNUAL MEETING Super Early Bird Rates

Take advantage of our lowest all year for our 28th Annual Meeting taking place in San Diego, California, October 19-22, 2017! http://aipm28.eventbrite.com STAY UPDATED Get Our Free Digital Publications in Your In-Box

Sign up to receive our bi-weekly e-newsletter — packed with research about integrative pain management — and the digital edition of our print magazine, The Pain Practitioner, which features bonus pain management content. http:// goo.gl/aQXf7p 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

Editor Debra Nelson-Hogan Advertising and Sales Sheila Miller Managing Editor Cathleen Coneghen Clinical Editor Christine Rhodes, MS Art Director Peter McKinley, Pak Creative 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.

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

NOTES FROM THE FIELD

What’s Missing from this Puzzle?

By Bob Twillman, PhD, FAPM, Executive Director

Some people find working jigsaw puzzles to be a great way to spend their quiet time. Many of us who have done this recognize the frustration felt when, after finding the right places for the first 499 pieces, the 500th piece turns up missing! That sense of frustration and incompleteness is what I’ve been feeling in the wake of two recent government announcements regarding the opioid overdose crisis.

THE SURGEON GENERAL’S LETTER The first announcement came on August 25, when US Surgeon General Vivek Murthy, MD, took the unprecedented step of writing all 2.3 million prescribers in the United States, asking them to sign a pledge to change their ways when prescribing opioid analgesics. Specifically, the letter requests that prescribers: 1) educate themselves about safe and effective pain treatment, citing the CDC Guideline for Prescribing Opioids for Chronic Pain; 2) screen patients for opioid use disorder and see that evidence-based treatment is provided when needed; and 3) talk about, and treat, addiction as a chronic illness, not a moral failing.

We can all agree that more education, better screening, and approaching addiction as a medical condition are all good things.

Opposing those would be like opposing motherhood and apple pie, and I sincerely hope that every prescriber will take this advice to heart. The challenge is that, while we have here three pieces of a puzzle, there is an important fourth piece that is missing.

DEPARTMENT OF HEALTH AND HUMAN SERVICES ANNOUNCES GRANTS Six days later, the US Department of Health and Human Services (HHS) announced that it was granting $53 million to 44 states, four tribes, and the District of Columbia to support various efforts to address drug abuse. These grants fall into six categories, and cover the spectrum of public health interventions, including enhanced surveillance, primary prevention, secondary pre-

vention (increased screening and related intervention), and tertiary prevention (medicationassisted treatment for addiction).

Again, this is a nice combination of efforts, and singly and in combination, they are all laudable. But the big problem for us is the missing seventh piece of the puzzle.

THE MISSING PIECE Missing from both of these initiatives is any mention of pain treatments that are alternatives to opioids. Both efforts drive home the message that health care providers must stop prescribing so much opioid medication in order to minimize opioid abuse, addiction, and overdose. One can argue about whether or not this will be an effective intervention, but the inescapable fact is that a piece of the puzzle is missing: What are clinicians to do if they don’t prescribe opioids?

Every behavioral health specialist worth his or her salt will say that a cardinal rule is this: Never take something away without providing a replacement. The Surgeon General and HHS both are proposing that we take away opioid prescribing, without carefully specifying that doing so for someone who is benefitting from opioid therapy could be harmful, not helpful. My question for Dr. Murthy and his HHS colleagues is: Why isn’t there ANYTHING here about the use of non-opioid treatments for pain?

Where is the support for the integrative approach to pain care that the CDC guideline recommends, and that we all know is the only safe and sane way to treat pain?

THE MISSING PIECE FOUND? Just as I was despairing and once again throwing up my hands in frustration, another government agency rode to the rescue. On September 1, the National Center for Complementary and Integrative Health (NCCIH) issued a report summarizing current scientific evidence for complementary health approaches for chronic pain. This report suggests that some complementary health approaches can help patients manage some types of chronic pain.

Couple this with a report from the Army Surgeon General’s Pain Management Task Force, which recommends that six key non-pharmacologic treatments (acupuncture, yoga, chiropractic/ osteopathic manipulation, massage therapy, biofeedback, and mind-body therapies) be made available to every current and former service member with chronic pain, and you have some pretty good recommendations.

These treatments are the missing piece of the puzzle because they can replace some portion of opioid therapy, minimizing both exposure that could lead to an opioid use disorder and excessive prescribing that leaves behind unused opioids for misuse, abuse, or diversion.

Now we know what the missing piece looks like, but why is it missing? There are a number of reasons, including inadequate education for “traditional” clinicians about these techniques and their uses; a shortage of clinicians providing these treatments, especially in rural and other underserved areas; and reimbursement that is often absent, and frequently inadequate when it is present.

For instance, of the six modalities mentioned by the Task Force, Medicare covers only a few types of chiropractic and osteopathic manipulations, and then only for some diagnoses. It covers none of the rest, unless those mindbody therapies are taught in the course of psychotherapy.

Addressing prescription opioid abuse is a complicated and arduous task, requiring multiple approaches. While the government is stepping up, as evidenced by these recent actions, we need to keep pointing to the missing piece that is support for integrative pain care, and demanding that they help us find and install that piece.

That has been, and continues to be, the primary focus of AIPM’s policy advocacy efforts.❏

TH E PAIN PRACTITION ER

Bob Twillman, PhD, is the executive director for the Academy of Integrative Pain Management.

| VOLUME 26, NUMBER 5 |

9

MEMBERSHIP

Shared Interest Groups Gather, Grow at Annual Meeting

CONTRIBUTORS Donations support the vital work of the Academy’s policy and advocacy efforts. We would like to thank the following contributors: Avani P. Sheth, MD Donna Flynn, PA Marsha R. Stanton, PhD, RN Martin Jay Porcelli, DO Odeane A. Connor, MD Rolando Amadeo, MD Theodor Parada, MD William Edward Guptill, MD 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.

Our new Shared Interest Groups (SIGs) are up and running! We’ve had more than 100 members sign up to participate and we are open to more. This membership benefit program will enable you to connect, collaborate, and engage with other like-minded experts. Please contact Whitney O’Donnell (wodonnell@ aapainmanage.org) if you are interested in sharing your expertise and knowledge.

Shared Interest Groups are intended to create a sense of community among AIPM members around topics of mutual interest. Once established with at least 10 dues-paying members, SIGs will be supported by AIPM staff as each creates a mission statement and begins to carry out activities to achieve that mission. The AIPM will assist SIGs in recruiting new members through a variety of means, and as groups grow, the level of support provided will increase. Established SIGs can participate in AIPM programs by writing articles in The Pain Practitioner, hosting sessions or even tracks of sessions at the Annual Meeting, creating training courses and/or certificate programs, hosting webinars, and in a number of other ways. Our most sincere hope is that every AIPM member finds a “home within a home” in one or more SIGs. Here is an update on each group’s progress, following our Annual Meeting in San Antonio.

FEDERAL MEDICINE: ESTABLISHING A NETWORK OF INTEGRATIVE PAIN CARE CHAMPIONS IN MEMORY We honor the memory of the following deceased members: Andrew W. Krasuski, MD Jerry L. Franz, MD Susan Best, MD

10

Training and education for Federal Prescribers mandated by the October 2015 Presidential Memorandum addressing prescription drug abuse and heroin use were discussed in this group. The goal of this SIG is to expand awareness and participation in Federal Medicine pain management initiatives, as well as develop presentations and posters on Federal Medicine pain management studies and best practices for the 2017 AIPM Annual Meeting.

NUTRITION IN PAIN MANAGEMENT: ADEQUATE NUTRITION IS A BASIC PREMISE OF GOOD HEALTH AND PAIN RELIEF This group discussed how to make nutrition interventions in the pain clinic feasible, especially when access and coverage may not be ideal. Participants noted several novel programs, including the use of subsidized farmers’ markets, educational “field trips” to supermarkets, and an antiinflammatory diet cooking class.

A potential “nutrition toolkit,” a compilation of ways a clinic could bring nutrition education to its patients, may be a goal for this SIG. Also, participants will gather handouts, demonstrations, and other materials, and post them online so that pain clinicians can easily provide point-of-care resources.

PAIN REHABILITATION: ADVANCING NON-PHARMACOLOGICAL REHABILITATION TECHNIQUES This diverse group is focused on improving the precision of language/vocabulary (e.g., integrative medicine vs. integrative therapies, patient-centered care, non-pharmacological care, etc.) used by health care providers, researchers, government agencies, insurance companies, media, and patients. They’d like to train clinicians and systems (private and public), on how to create models of integrative pain care.

This SIG will collaborate on journal articles to address important clinical issues shared across multiple disciplines. When this group expands, it would like to offer a session at the AIPM Annual Meeting summarizing its research on cost savings, outcomes, and practical solutions to clinical challenges.

PALLIATIVE CARE: ADVANCING THE QUALITY OF LIFE FOR THOSE WITH SERIOUS, LIFE-LIMITING ILLNESS Participants in this group discussed the management of symptoms in cancer survivors, who are a different kind of chronic pain patient. These patients don’t

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fit squarely in the hospice bucket or the non-cancer chronic pain bucket. This SIG’s goal is to generate high-quality review articles for The Pain Practitioner and the planned Journal of Integrative Pain Management to help educate colleagues about best practices in palliative care.

BEHAVIORAL HEALTH: ADDRESSING MENTAL HEALTH AND SUBSTANCE USE DISORDERS The Behavioral Health SIG addressed limitations members experience when working in medical settings. Participants addressed the need to educate medical providers about reimbursement, training students on the biopsychosocial model and its implementation, conducting nurse and social worker training programs, and carrying out medication management evaluations, all geared toward behavioral health issues. Concerns related to proper and effective coding and billing for behavioral health issues in people with chronic pain also were discussed. Finally, the group discussed forming subcommittees to focus on the following functions: advocacy, legislation, education and training, and programming.

MYOFASCIAL THERAPY Spontaneously formed at the Annual Meeting, the Myofascial Therapy SIG held its initial organizational meeting. Participants discussed a range of therapies including trigger point interventions, acupuncture, chiropractic, cold lasers, LEDs, and others.

The group also talked about single-specialty clinicians who provide a range of treatments, such as dentists who treat not only TMJ disorders, but sleep apnea and other issues. The goal for this group is to offer a lecture series or hands-on workshop at the 2017 AIPM Annual Meeting. ❏

ANNUAL MEETING / EDUCATION

THE 27TH ANNUAL MEETING:

Sweet Validation for Business as Usual

By Christine Rhodes, MS

(Left), Robert Bonakdar MD, FAAP, (Center), M. Catherine Bushnell, PhD, ( Right), Seddon Savage, MD, MS

The 27th Annual Meeting of the Academy of Integrative Pain Management (AIPM, formerly the American Academy of Pain Management) was held in San Antonio against the backdrop of breathtaking Texas hill country views, reminding attendees that they are indeed on the frontier of medicine as members of the only organization that has been dedicated exclusively to integrative pain management since 1988. This year, in addition to the educational sessions, shared interest group meetings, exhibits, and professional networking, the newly released National Pain Strategy (NPS) was very much in evidence together with the Guidelines for Prescribing Opioids for Chronic Pain concurrently released by the Centers for Disease Control and Prevention (CDC) (1,2). The National Pain Strategy validates the approach to pain care that the Academy has been advocating since its inception.

On Thursday night, Academy Board of Directors President Joanna Katzman, MD, MSPH, welcomed the 2016 attendees and introduced the members of the Board. The execu-

tive director of the Academy, Bob Twillman, PhD, kicked off the meeting by introducing keynote speaker Linda L. Porter, PhD, director of NIH’s Office of Pain Policy, National Institute of Neurological Disorders and Stroke, and co-chair of the Interagency Pain Research Coordinating Committee’s (IPRCC) working group that helped to develop the report. Dr. Porter described the National Pain Strategy, the government’s first broad-ranging effort to improve how pain is perceived, assessed, and treated, as a significant step toward the ideal state of pain care. With 100 million American adults reporting chronic pain, according to the Institute of Medicine’s 2011 report, Relieving Pain in America (3), implementation of the NPS is intended to provide better pain care, while reducing the need for prescription opioids.

In his keynote session, AIPM’s immediate past president, Robert A. Bonakdar, MD, FAAFP, director of Pain Management at Scripps Center for Integrative Medicine and assistant clinical professor at UCSD School of Medicine, addressed

the evolution of alternative pain treatments used around the world and showed how these approaches may inform and improve access and quality of US pain care. The United States has the highest use of opioids for pain and the highest rate of deaths from opioids, yet diagnostic testing and medical and surgical procedure rates are also the highest.

Morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations (4). Dr. Bonakdar noted that “the pain transformation called for by the IOM and most recently the National Pain Strategy requires not just a campaign, but an integrative, patient-centered approach to support someone whose entire existence is affected.”

As plenary speaker M. Catherine Bushnell, PhD, explained, chronic pain has consequences that go far beyond the pain itself, with patients showing anxiety, depression, and cognitive deficits. Moreover, brain imaging studies show that chronic

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ANNUAL MEETING / EDUCATION

pain causes alterations in brain anatomy and function. Through her work as scientific director, Division of Intramural Research, and senior investigator, Pain and Integrative Neuroscience Branch (PAIN), at the National Center for Complementary and Integrative Health, Dr. Bushnell and her colleagues have shown how these effects can be prevented or reversed by environmental factors.

We know, for example, that such lifestyle factors as increased exercise and decreased stress are important in improving patients’ experience of pain. Now, research shows that such practices can actually change the brain, and yoga specifically has been shown to protect against age-related grey matter loss and increase pain tolerance. Such findings provide the scientific evidence for what many AIPM members have long known and advocated for their patients.

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CHRONIC PAIN AND ADDICTION However, no discussion of chronic pain can take place without also discussing opioid prescribing practices and addiction. Indeed, the National Pain Strategy provides a path to reducing the need for prescription

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opioids and their safer use. Seddon Savage, MD, MS, medical director of the Chronic Pain and Recovery Center at Silver Hill Hospital and noted advocate in pain medicine and addiction, presented an overview of the intersection between chronic pain treatment and addiction. She described several of the mechanisms whereby opioids could actually facilitate pain, including opioid-induced hyperalgesia, withdrawal-mediated pain, and pain caused when patients feel such relief that they increase their activities. Interestingly, she also speculated whether opioid addiction could increase an individual’s perception of pain to satisfy a craving for opioids as well as reinforce the condition of chronic pain. Finally, she presented research showing the long-term benefits of a treatment approach for patients with chronic pain and addiction.

With the increasing recognition that opioid abuse is indeed an epidemic, and that nearly 35% of patients with chronic pain have some type of substance use disorder (5), Michael Sprintz, DO, founder of the Sprintz Center for Pain and Dependency, called for clinicians to acknowledge the “elephant in the room” by not shying away from treating pain but also understanding the neurobiology of addictive disease. He encouraged clinicians to step out of their comfort zones by learning to identify patients with a potential substance use dis-

ANNUAL MEETING / EDUCATION

Linda L. Porter, PhD

order and adopting an integrative approach to pain management.

Key to an integrative approach are providing structure for patients, in the way of aggressively managing their care and involving their family members in treatment, and communicating with other health care providers to form a network of referral partners who can provide more comprehensive pain and addiction care, as well as provide behavioral health and other non-pharmacological health services. He mentioned that it is important to find colleagues who accept insurance, a point that is seldom discussed but is central to the opioid epidemic.

Dr. Bonakdar also highlighted the shortsightedness of insurers in his presentation when he gave several examples of health systems that are adopting the use of comprehensive biopsychosocial self-management programs that incorporate treatments such as acupuncture and massage to the benefit of patients and payers.

While the undercurrent of the National Pain Strategy was strong and ran throughout the meeting sessions, many presenters did what has always been done at the American Academy of Pain Management annual meetings, and that is, talk about various integrative treatments for chronic pain. From myofascial pain to complex regional pain syndrome, to phantom limb pain, to migraine, to fibromyalgia, all presenters acknowledged the complex interrelationship of physiologic, psychologic, and social factors involved in these conditions’ causes and treatment. Attendees also had the opportunity to attend early morning movement and meditation sessions. A new feature this year was “Short Shots: 30-Minute, Targeted Sessions,” giving the busy attendee quick doses of learning on such topics as diet and nutrition, yoga, and massage. And, of course, no annual meeting is complete without the

exhibitors and their products and services. As always, there was ample time for attendees to tour the exhibit hall, as well as attend the President’s Reception and the Exhibitors’ Receptions. Poster abstracts were also on display, and the award-winning abstracts are presented on page beginning on page 31. ❏ Christine Rhodes has an MS in nutrition and is a medical writer based in New York City. Besides serving as clinical editor of The Pain Practitioner, she is a Certified Holistic Health Coach, American Association of Drugless Practitioners.

References 1.

2.

3.

4.

5.

National Pain Strategy. A Comprehensive Population Health-Level Strategy for Pain. https://iprcc.nih.gov/docs/HHSNational_Pain_Strategy.pdf. Accessed October 3, 2016.

Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016.

JAMA. 2016;315(15):1624-1645.

Institute of Medicine. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. IOM Committee on Advancing Pain Research, Care, and Education Board on Health Sciences Policy. 2011.

Murray CJ, Atkinson C, Bhalla K, et al. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA. 2013;310(6):591-608.

Boscarino JA, Rukstalis MR, Hoffman SN, et al. Prevalence of prescription opioid-use disorder among chronic pain patients: comparison of the DSM-5 vs. DSM-4 diagnostic criteria.

J Addict Dis. 2011;30(3):185-194.

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ADVOCACY

The Power of a Network

By Amy Goldstein, MSW, Director of the State Pain Policy Advocacy Network

Amy Goldstein, MSW, as the inaugural Director of the State Pain Policy Advocacy Network (SPPAN) for the American Academy of Pain Management, has developed a collective vision to shape person-centered pain policies. Bringing her demonstrated success in the policy and advocacy arena, she continues to cultivate effective alliances among advocacy leaders, create needed resources to educate and promote action on timely state and federal policies relevant to pain care, and lead a team to implement SPPAN’s policy priorities.

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FINDING HIDDEN TREASURES TO ADVANCE INTEGRATIVE PAIN CARE

What does a hopeful future for accessible and affordable integrative pain care look like and what policy changes can get us there? Depending on whom you ask, answers might range from “Advocating will get us there” to “Zero chance for better policies” and anything in between. Here at the State Pain Policy Advocacy Network (SPPAN), a project of the Academy of Integrative Pain Management, we remain optimistic and focused on our goals to support a better landscape for integrative pain care policy. Nimbly, we listen to and learn from a wide variety of stakeholders and adjust our strategies for greatest impact, always aiming for the ultimate goal of ensuring that patients have access to the optimal treatment or treatments for their individual conditions.

SIFTING FOR STRATEGIES At a local farmstead over the summer, I watched my sons’ delight as the water washed over their bucket of sand at the “rock mine” to reveal hidden gemstones. In a similar way, SPPAN brings people and ideas together and, through robust discussion, we sift through many challenges to find hidden—or obvious—treasures or opportunities that will advance our policy priorities. We then facilitate collective action to implement them.

In August, SPPAN convened its Leadership Advisory Council members and other invited content experts for our 4th annual strategic planning meeting. We offer our sincerest thanks to the American Academy of Family Physicians, one of our partners, for sharing their meeting space in Overland Park, Kansas, for these important discussions.

Two dozen leaders came together for a networking dinner followed by a day-and-a-half of meetings to discuss their shared policy priorities, combining clinical, policy, and legal expertise that represented the perspectives of physicians, nurses, pharmacists, integrative health care practitioners, people living with chronic pain, palliative care and cancer, and more.

Several hours were slated to discuss improving access to integrative pain care, our highest policy priority.

To ensure all participants were working from the same baseline of information, we first discussed what integrative pain care is, what is happening in the integrative care “space,” trends in health policy, action related to relevant state and federal bills, and related laws that affect daily practice. Then we pivoted to a draft of a new bill that our SPPAN team created to advance access to care, asking our expert participants to critically analyze every line. This robust discussion uncovered numerous opportunities to improve the approach we will be taking to create new policies that advance integrative pain care. In addition to this topic, our packed agenda included discussions about pain management practice guidelines, prescription monitoring programs, overdose reversal, public safety, network adequacy, and relevant federal issues such as the National Pain Strategy and the Comprehensive Addiction and Recovery Act of 2016 (CARA).

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SPPAN is uniquely positioned to listen closely to both a diverse group of people living with pain and a wide range of health care practitioners and policy experts. With our eye on outcomes in 2017, we are working behind the scenes to consider what combination of policy activities will be most effective to connect the dots for the millions of people living with serious pain. The gold standard for caring for someone with pain has, at its core, a thorough assessment, identified goals, and ongoing communication between the patient and practitioner to identify risks and benefits to achieve the best course of action. This multimodal approach for personalized care requires that a wide range of treatments are affordable and accessible to patients and understood by clinicians. The conversations being heard around our country are finally showing us that many lawmakers have realized that pain management does not equal opioid prescribing—and further, that policies must change so that an integrative, multimodal approach becomes the standard of care AIPM and SPPAN have always known it to be. The devil is in the details, as they say, as we must identify where we can agree with many stakeholders and balance that with an outcome that will truly help people get what they need to live a healthier, higher functioning quality of life. Stay tuned for an update, as our strategies for 2017 are refined and tweaked for maximum impact.

WE’RE IN THIS TOGETHER SPPAN and AIPM are committed to working with others to influence pain policies that result in the ability to deliver, and receive, integrative, multimodal pain care. We want to hear from you and learn more about what you are experiencing in your state. Reach out to the SPPAN Director, Amy Goldstein, at agoldstein@aapainmanage.org. And visit our website for timely and relevant information at www.sppan.aapainmanage.org. ❏

PROFESSIONAL DEVELOPMENT

Satisfy State CME Requirements in our Pain Care Learning Center

By Debra Nelson-Hogan, Director of Professional Development

Many of you need to take a specified number of continuing education courses in order to maintain your license or to continue to prescribe controlled substances.

The AIPM has a growing library of online courses that comply with many of those CME requirements. One excellent option is to take the online Curriculum Review Course—14 hours of accredited education that was developed in 2015 to help those who were planning on taking the Advanced Credentialed Pain Practitioner exam. The program, which is centered on a thorough and comprehensive curriculum, is designed to create a knowledge base for primary care practitioners who spend a significant portion of clinical time treating commonly encountered pain conditions, but who may not be practicing at a fellowship-trained level. It is also an outstanding review of pain management for those who are currently in the field.

The Curriculum was compiled by George D. Comerci, Jr., MD, FACP, professor of internal medicine in the department of internal medicine at the University of New Mexico (UNM) School of Medicine, Brian M. Shelley, MD, director of Albuquerque Independent Medical Services, LLC, and clinical associate professor of the UNM department of family and community medicine, and Daniel J. Duhigg, DO, MBA, assistant professor of psychiatry at UNM and director of the UNM Fellowship in Addiction Psychiatry. Content for the curriculum was provided by leaders in the pain field.

The content for the online course is detailed and thorough and consists of the following: The Basics of Pain Management This overview includes the epidemiology of chronic pain in the United States, a discussion of the principal anatomic divisions of the nervous system involved in nociception, and

the physiologic mechanisms involved with nociception from receptor to cerebral cortex.

Pain Assessment This section includes the general principles of physical examination of the musculoskeletal and neurological systems, key anatomic features of body regions that require physical examination, and specific musculoskeletal and neurological exam maneuvers that enhance disease detection. It also includes sections on imaging, electrodiagnosis, and a detailed discussion on the benefits of the patient-centered interview.

Psychology of Pain This module describes the basic components of the mental status exam, screening and assessment tools for depressive disorders and anxiety disorders, and somatic symptom and related disorders. It also includes non-pharmacologic and pharmacologic treatments for depressive and anxiety disorders and a review of patients with co-morbid chronic pain and substance use disorders.

Pain States Specific segments focus on common pain disorders, including headache (primary, secondary, cranial neuralgias, ominous headaches, and temporomandibular dysfunction), fibromyalgia, complex regional pain syndrome, pelvic pain, myofascial pain and pain involving the axial spine. Discussion of these conditions includes their clinical features and treatment options.

Pharmacotherapy There are specific sections for non-opioid medications, opioid therapies, and supplements, botanicals, and nutraceuticals.

The non-opioid medications include the various categories of non-opiate pain medications, and the indications, safe usage, and contraindications of a prototypical medication from each category of non-opiate pain medications. There are specific sections on anti-spasticity medications, anti-spasmodic medications, topical medications, and other medications for pain. The serotonin syndrome and Beers Criteria are also covered.

The module on opioid therapy includes a review of opioid pharmacology and a discussion of common opioids. It includes

• Who is at Risk for Opioid Addiction: How do I know?, Daniel Duhigg, DO • The Future of Pain Management: The Role of Self-Care and Integrative Collaboration, Wayne Jonas, MD

The section on supplements, botanicals, and nutraceuticals covers the evidence supporting the use of several common analgesic dietary supplements and their the safety and quality.

Interventional Techniques This segment covers the procedure of trigger point injections and the evidence for spinal interventions.

Integrative Treatment Modalities This program discusses several integrative treatment modalities, including the evidence for using acupuncture to treat various chronic pain conditions, the benefits of mindfulnessbased stress reduction, and the evidence for using Tai Chi to treat fibromyalgia.

Unique Populations This section covers the specifics of treating pediatric and geriatric patients.

Self-Care This program reviews different self-care activities for both the patient and the practitioner.

Regulatory Issues This program gives a good overview of the key regulatory issues in pain management and includes a discussion of the four types of regulatory policy with examples of each one. It details the requirements under federal law for prescribing and dispensing controlled substances and describes the role of controlled substance agreements in the context of chronic pain management. It also covers the purposes and key characteristics of prescription drug monitoring programs (PDMPs).

Ethics of Pain Treatment This presentation discusses the core concepts of beneficence, non-malfeasance, autonomy, standard of decisional capacity, and the ethical dilemmas commonly encountered in chronic pain management.

Interdisciplinary Chronic Pain Management (ICPM) Team This session defines Interdisciplinary Chronic Pain Management (ICPM), the structure of the ICPM team, and the benefits of ICPM.

Registration

OTHER POPULAR COURSES IN THE PAIN CARE LEARNING CENTER INCLUDE: • A Comprehensive Overview of Complex Regional Pain Syndrome, Philip Getson, DO

clinically significant opioid side-effects, potentially lethal combinations, indications of opioids, and guideline-based use of opioids.

• Is it Myofascial Pain, Fibromyalgia, Migraine, or Chronic Widespread Pain: A Differential Diagnosis, Joanna Katzman, MD, MPH • Trusting Your Patients: Objectivity and Subjectivity in Health and Health Care, Peter Moskovitz, MD

This 14-hour program is designed for physicians, nurse practitioners, and physician assistants as well as other clinicians who treat chronic pain.

Registration for AIPM members is $1,500 and for non-members is $1,750. For more information, visit education.aapainmanage. org, email credentialing@aapainmanage.org, or call 209-288-2205.

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RESEARCH / CURRENTS

Research Recap Every other week, Currents, the AIPM’s e-newsletter, publishes research and guidelines on issues related to chronic pain. You can subscribe to Currents and the digital version of The Pain Practitioner from this link: http://blog.aapainmanage.org/ notifications-the-pain-practitioner/.

Below are the research highlights from Currents.

EFFECTS OF LONG- AND SHORTTERM INTERDISCIPLINARY TREATMENT APPROACHES IN WOMEN WITH FIBROMYALGIA: A RANDOMIZED CONTROLLED TRIAL.

Both long- and short-term interdisciplinary treatments were effective in reducing the severity of some symptoms and disease activity in patients with fibromyalgia. The short-term program well meets the needs of women with fibromyalgia, particularly in relation to pain and health status as measured using the Fibromyalgia Impact Questionnaire (FIQ); however, a long-term program may be beneficial in reducing fatigue and improving physical function to a higher extent.

Read more: http://link.springer.com/ article/10.1007/s00296-016-3473-8

FACTOR STRUCTURE OF THE ARTHRITIS-RELATED HEALTH BELIEF INSTRUMENT IN ETHNICALLY DIVERSE COMMUNITY-DWELLING OLDER ADULTS WITH CHRONIC PAIN.

Nonpharmacological treatment of chronic pain in older people can be effective, but attitudes and adherence to use of this treatment may differ by ethnicity. This study supports that a modified 14-item instrument based on the modified Health Belief Model—the arthritisrelated health belief instrument (AHBI)—can be used across ethnically diverse older adults. Read more: http://link.springer.com/article/10.100 7%2Fs10900-014-9898-7

TOUCH PERCEPTION ALTERED

BY CHRONIC PAIN AND BY OPIOID BLOCKADE.

Based on observations in animal studies, these researchers studied the role of endogenous opioids in perception of affective touch in healthy adults and in patients with fibromyalgia. The study administered naloxone to patients and healthy controls to directly observe the consequences of µ-opioid blockade on the perceived pleasantness and intensity of touch. A differential effect of opioid blockade on touch perception in healthy subjects and

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pain patients was found. In healthy individuals, opioid blockade showed a trend toward increased ratings of touch pleasantness, while in chronic pain patients it significantly decreased ratings of touch intensity.

These findings suggest a role for endogenous opioids in touch processing, and provide further evidence for altered opioid functioning in chronic pain patients. For a free link to the full text, go to: http://www.ncbi.nlm.nih. gov/pmc/articles/PMC4785385/

personal reflections of participants, establishing new ways of working requires negotiating space and place to practice, role clarification, and frequent and effective modes of formal and informal communication to nurture the development of trust and mutual respect, which are vital to success. Read more: http:// www.ncbi.nlm.nih.gov/pmc/articles/ PMC4736701/

Studies also show that the use of pain assessment tools appropriate to a child’s age and cognitive development play a vital role in improving pain assessment documentation, prompting nurses to provide pain medication. This quality improvement project was conducted to improve nurses’ assessment and management of children’s pain in an emergency department. Read more: https://www.unboundmedicine.com/ medline/citation/27019942/Pediatric_Pain_Management:_An_Evidence_Based_Approach_

prescribers of opioid analgesics, and surgical tooth extraction is one of the most frequently performed dental procedures. This JAMA research letter examines the frequency of opioid prescriptions filled within seven days of extraction among Medicaid patients. Link: http://jama.jamanetwork. com/article.aspx?articleid=2503505

TEN YEARS OF OPIOID PRESCRIBING DATA AFTER EVIDENCE SUGGESTS THAT NURSES’ SURGICAL EXTRACTION OF TEETH LACK OF KNOWLEDGE ABOUT PAIN There is little information available ASSESSMENT IN CHILDREN on nationwide patterns of opioid prescribing following tooth extracCONTRIBUTES TO INADEQUATE tion. Dentists are among the leading PAIN MANAGEMENT.

LONGITUDINAL EVIDENCE OF A NON-LENGTH-DEPENDENT DISTAL AXONOPATHY.

Peripheral neuropathy typically follows a length-dependent pattern, leading the researchers to hypothesize that patients with small fiber neuropathy (SFN) would lose intraepidermal nerve fibers at the distal leg more quickly than at more proximal thigh sites. In this longitudinal, case-control study, patients diagnosed as having SFN underwent additional evaluation at tertiary outpatient neurology clinics. The study showed epidermal nerve fibers were lost at similar rates in proximal and distal sites, suggesting that SFN is a non-length-dependent terminal axonopathy. Read more: http:// archneur.jamanetwork.com/article. aspx?articleid=2511289#tab1

EXPLORING INTERPROFESSIONAL COLLABORATION DURING THE INTEGRATION OF DIABETES TEAMS INTO PRIMARY CARE. Findings provide insight into how health care professionals who have not traditionally worked together in primary care are collaborating to integrate health services essential for optimal diabetes management.

Based on the experiences and

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SPINAL PAIN: CURRENT UNDERSTANDING, TRENDS, AND THE FUTURE OF CARE.

This commissioned review paper offers a summary of current understanding of nonmalignant spinal pain, particularly persistent pain. Spinal pain can be a complex problem, requiring management that addresses both the physical and psychosocial components of the pain experience.

The authors propose a model of care that includes the necessary components of care services that would address the multidimensional nature of spinal pain. Emerging care services that tailor care to the individual person with pain seem to achieve better outcomes and greater consumer satisfaction with care, while most likely containing costs. However, the authors recommend that any model of care and care framework should be developed on the basis of a multidisciplinary approach to care, with the scaffold being the principles of evidence-based practice. Importantly, the authors propose that any care services recommended in new models or frameworks be matched with available resources and services— this matching they promote as the fourth principle of evidence-based practice. Ongoing research will be necessary to offer insight into clinical outcomes of complex interventions, while practice-based research would uncover consumer needs and workforce capacity. Link: http://www.ncbi. nlm.nih.gov/pubmed/26604815

BIOFEEDBACK

Heart Rate Variability, Chronic Pain, and Rehabilitating the Autonomic Nervous System

A

BY RAOUF GHARBO, DO, AND J.P. GINSBERG, PHD

ssessments of heart rate variability (HRV), or the variability of the interval between consecutive heartbeats, have emerged as a powerful and easily measured biomarker of brain-body disorders, including some forms of chronic pain(1). Results of our pilot study of HRV biofeedback (HRVB) show its promise as a treatment for non-malignant pain in veterans (2) and have led to an early Phase I VA-funded randomized, controlled trial. In addition, preliminary data for HRVB as a treatment for cancer pain are promising.

HRV is not random or background noise. Research on HRV began in the 1960s when electronic signal processing facilitated its measurement and analysis. In the 1980s, we learned that mortality was five times greater in myocardial infarction patients with the lowest HRV than in patients with moderate HRV (3). We now know that HRV is a predictor of future health issues besides pain, including cardiac and cardiovascular disease; asthma; diabetes; stress, anxiety, post-traumatic stress disorder (PTSD), and depression; concussive brain injury; autonomic nervous system (ANS) dysfunction disorders like postural tachycardia syndrome (POTS); and sudden infant death (4,5).

Respiratory Sinus Arrhythmia The HRV rhythm of low to high interbeat intervals occurring in synchrony with the respiratory cycle is known as respiratory sinus arrhythmia (RSA). RSA is actually a healthy arrhythmia.

The amplitude of RSA, and therefore HRV, is maximized during resonance breathing, which occurs at approximately six breaths per minute in most people. Along with sufficient sleep and appropriate exercise, inducing resonant RSA may be an extremely beneficial health modifier (6). Since first being studied in Soviet Cosmonauts in the 1980s, and echoed in current literature by Paul Lehrer (7), resonant breathing has proved to be the most validated technique for optimizing HRV. Resonant breathing is a central component of HRVB. When a large diaphragmatic muscular excursion is in sync with the heart muscle we see a harmonious and amplified HRV rhythm called coherence. Coherence is the most efficient state for recovery from

stress. As the heart muscle efficiently coasts in sync off its secondary pump, resting heart rate will lower. The greater the influence the diaphragm has on the heart rhythm, the greater the HRV, and the greater an individualâ&#x20AC;&#x2122;s physical and emotional health and resilience.

Studies conducted in the past two decades have shown that resonant RSA or coherent HRV improve health by increasing the impact of autonomic system function on sympathetic-parasympathetic influences on the heart (8-10). The beneficial use of HRVB for pain management has been studied and documented by several clinical researchers (1113), which should propel the use of HRV for both pain management assessment and treatment.

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We now know that HRV is a predictor of future health issues besides pain, including cardiac and cardiovascular disease; asthma; diabetes; stress, anxiety, posttraumatic stress disorder (PTSD), and depression; concussive brain injury; autonomic nervous system (ANS) dysfunction disorders like postural tachycardia syndrome (POTS); and sudden infant death.

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BIOFEEDBACK

Versatile handheld commercial biofeedback devices have become easily available, and prescribing resonant RSA for 10 minutes twice daily and more often if needed is a reasonable clinical practice for health. Adding coherent HRV prior to sleep improves cardiorespiratory resting function and, consequently, sleep quality (14).

Often we find that chronic pain sufferers crave being pain free, have racing brain insomnia, and develop helplessness from unremitting kinesophobia (fear of movement). A habit of resonant breathing twice daily and more often if needed seems to provide a calming period of RSA that enables pain sufferers to reduce the ruminations that lead catastrophizing, which research shows is a powerful predictor of postsurgical pain (15,16). Shifting emotion to a positive emotion like gratitude regardless of breathing rate or HRV coherence can be a difficult skill to learn, but can be done with biofeedback and good coaching (17)..

In the clinical setting, we use a car racing analogy to teach increased self regulation of the ANS and fear-avoidance behaviors. As a professional Formula 1 driver speeds into a curve they will engage left foot braking for immediate control while maintaining some gas to maintain speed. We can maximize the (parasympathetic) relaxation response braking system with resonant RSA breathing during life’s unpredictable (sympathetic) twists and turns. Awareness under stress improves with both arms of the ANS fully engaged. Rather than avoiding stress and fear, one realizes it is as necessary for arousal during hairpin turns as it is for managing unhealthy habits. Eventually, one will have to make a second choice to enter a peaceful recovery pit stop. Often, that means easing off the gas pedal in some manner.

Introducing a habit of engaging ANS Left Foot Braking under duress is the beginning for making healthy choices.

The science of defining a low-resource, reproducible ANS rehabilitation method is emerging (18). HRV assessment and biofeedback will become foundational elements for individualized multimodal integrative ANS rehabilitation pain management plans. ❏ Raouf (Ron) Gharbo DO,

is a physical medicine and rehabilitation and integrative pain management specialist, neuromuscular electrophysiologist, and assistant clinical professor at Eastern Virginia Medical School, Newport News, Virginia.

J.P. (Jack) Ginsberg, PhD, is a licensed clinical psychologist/neuropsychologist and principal investigator at the Dorn VA Medical Center, Columbia, South Carolina.

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References 1.

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3.

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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

PAIN MANAGEMENT GROUPS: REMEDY BY THE DOZENS

Pain Management Groups: Remedy by the Dozens

BY KAREN SPURGEON WELCH, MD, ABFM

W

e are no strangers to pain in todayâ&#x20AC;&#x2122;s medical climate. An estimated 1.5 billion people are suffering from chronic pain worldwide (1). National costs for pain exceed costs for cardiovascular disease, cancer, and diabetes combined, with societal costs totaling an astonishing approximately $600 billion annually in the United States. As patient demand for pain care rises, so does expenditure, along with unfortunate narcotic morbidity and mortality. Many of us are finding that group medical visits (GMVs) can help counter this crisis.

Group visits provide a much-needed solution in pain management and are growing in popularity for good reason. This format is a viable way to deliver therapies that can otherwise outgrow a 20-minute encounter. As Bonakdar, Sukiennik, et al., point out in Integrative Pain Management, many exciting non-opioid options for pain management exist (1), and GMVs provide space for education along with a whole-person approach that is optimal to deliver these remedies.

Therapies such as mindfulness, guided imagery, yoga, and tai chi are easily taught as part of a group visit. Delivery in a group setting normalizes such novel practices and encourages patients to

adopt behaviors that are outside of their comfort zone. These therapies call for action on the part of the patient, and the group setting can be a forum for exploring motivation and finding creative solutions to any barriers. Many facilitators employ tools such as motivational interviewing to guide participants in moving forward.

Pain is strongly impacted by co-morbid conditions such as anxiety and depression. As one can imagine, adverse mood intensifies pain and increased pain leads to poor mood in a brutal cycle.

These conditions are ideal for group management. Education about mood and mood management is largely generalizable. Importantly, group support in itself serves as a therapeutic remedy by alleviating common contributors including isolation and loneliness.

Consider Jim, a middle-aged man with chronic back pain. His primary doctor has asked him to cut back on narcotics. He doesnâ&#x20AC;&#x2122;t know anything else that works and desperately needs to manage his pain so he can keep his job and support his family. He is no longer able muster through the pain. He feels depressed and is frankly embarrassed to talk about his mood. Jim attends a group visit and is surprised to know that others have similar problems. He learns new ways to cope with pain. Hearing others talk about how pain affects mood and vice versa causes him to examine his own mood TH E PAIN PRACTITION ER

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Skeptical About Neurogenx?

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NEUROGENX is definitely a viable neuropathy treatment where other options have failed.”

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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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“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.

PAIN MANAGEMENT GROUPS: REMEDY BY THE DOZENS

in a new light. He leaves his visits feeling more informed, connected, and empowered.

As a family physician specializing in integrative and behavioral approaches at University of Texas Medical Branch-Health, I co-facilitate group visits for anxiety and stress management. Jim is a typical patient in our sessions. Patients like the approach and let us know by their turnout and feedback. I find this to be both a pleasurable and uniquely effective way to provide care. Patients often help each other in ways that I alone could not. Questions arise in a group setting spontaneously, and the group discussion leads to clarification for all. I am amazed in every session by the level of support provided between members and how this mutual support promotes healing.

Providers are experimenting with different models to best fit a given population. Integrative Pain Management chapter authors Geller, Truong, and Trowbridge describe a unique model for GMVs known as the Empowerment Model (EM), which is a useful forum for pain management (1). This type of GMV focuses on building relationships and trying new things and uses an open visit model, one that does not have predefined curriculum and allows for participants coming and going as desired.

An open visit model increases accessibility to those with transportation or other barriers who could not otherwise commit to a predetermined number of sessions.

Money talks, and as it turns out, group visits boast a desirable effect on the bottom line. While increasing patient and provider satisfaction, group visits are also proving to decrease overall health care spending and provide a way to deliver billable care to a room full of people in a span of two to three hours. Group medical visits are a savvy business model.

Pain management is a growing challenge in health care from perspectives of need, health care expenditures, and adverse effects of our most common therapies. We are in need of new ways to deliver safe and effective therapies. Consider treating yourself and your patients to a group medical visit as an innovative way to remedy pain by the dozens. ❏

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.

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 • Integrative therapies

Reference 1.

When Pain is More Complicated Turn to Sierra Tucson

Bonakdar R, Sukiennik AW. Integrative Pain Management. Weil Integrative Medicine Library. New York, NY: Oxford University Press; 2016.

Karen Spurgeon Welch, MD, ABFM, is a fellow in integrative medicine and behavioral health and clinical instructor in family medicine at the University of Texas Medical Branch at Galveston.

• Lifestyle skills building • 24-hour support

844-215-1400 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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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!

To get started, go to: education.aapainmanage.org OR FOR MORE INFORMATION: CONTACT CATHLEEN CONEGHEN AT CCONEGHEN@AAPAINMANAGE.ORG

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.

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CURRICULUM REVIEW COURSE 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.

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Save $150 if you sign up for the online course and the ACPP exam at the same time.

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2016 ANNUAL MEETING POSTERS Judges at the 27th Annual Clinical Meeting in San Antonio selected the blue ribbon posters from each of the following three categories: Original clinical research, basic science/review/case study, and student/fellow/ resident. They also identified posters worthy of an honorable mention. All are presented below: Blue Ribbon in Original Research Integrative Medical Group Visits: a Randomized Controlled Trial in Underserved Chronic Pain Patients Author and Presenter: Paula Gardiner, MD, MPH Background: Integrative medical group visits (IMGV) are a nineweek medical group for patients with chronic pain and depression.

It combines evidence-based integrative medicine techniques with a group medical visit to reduce pain and depressive symptoms. This randomized control trial took place in Boston.

Objective: To report the findings of the study from baseline to nine weeks.

Methods: Patients completed demographics questionnaires with trained RAs at baseline and nine weeks. The primary outcome measures include the Brief Pain Inventory (BPI) and Patient Health Questionnaire were also collected at nine weeks. Descriptive statistics and two-sided T tests will be used.

Results: Currently there are six completed cohorts and one in progress to end in August 2016. 107 participants have been recruited to this RCT to date. Most are female (86%), Black (60%), have some college education, are on sick leave or disability (47%), and make under $20,000 per year. Eighty-six percent of participants use a pain medication with 59% using opioids. The average pain score is 7 on a 1 to 10 scale. For the poster, we will report on the changes in pain and depression from baseline to nine weeks.

Conclusions: Participants in this RCT belong to a population that does not often get access to integrative medicine. The IMGV model could potentially allow for greater access to integrative medicine techniques and reduction of pain and depression.

References: n/a Disclosure: Study is supported by PCORI.

this moment to improve their situation. Nevertheless patients need to practice radical acceptance, learn new behaviors in all relevant contexts, and be more motivated to change. Patients may not have caused all of their problems, but they have the responsibility to solve them. Chronic pain patients often present with psychological and somatic issues that require supplemental therapies to traditional pain management. Emotion regulation, acceptance, and dialectical thinking are important factors associated with the development of issues related to persistent pain, usually varied anxiety, and depressive symptoms (2,3). DBT has proven effective in the treatment of complex emotional issues and in developing skills that could benefit patients suffering from pain related psychological distress. DBT is a therapy modality created in the US that offers a more structured and practical approach than Acceptance and Commitment Therapy (ACT) to working with acceptance and emotion regulation issues. Nevertheless, the use of ACT for pain management issues has been more widely researched, while the use of DBT has rarely been explored.

Objective: To propose the feasibility and acceptance of using Dialectical Behavioral Therapy to help patients alleviate distress and manage the emotions related to their chronic pain. The objectives of the proposition are to increase awareness of emotions, wellness, and life satisfaction as related to pain; to achieve learning of mindfulness methods and applications; and to promote acceptance and wellbeing as defined by DBT principles and theoretical underpinnings.

Methods: Conceptual/theoretical proposal Results: A defined intervention plan delineating a modified version of DBT for treating patients with pain management-related issues.

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Blue Ribbon in Basic Science/Review/Case Study

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Dialectical Behavioral Therapy (DBT) as a Tool to Help Manage Psychological and Emotional Aspects of Chronic Pain

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Presenter: Adriana Dyurich, MS, LPC-Intern; and Veena Prasad, MS

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Authors: Adriana Dyurich, MS, LPC-Intern; Veena Prasad, MS; A.R. Prasad, PhD, MD Background: Dialectical Behavioral Therapy (DBT) is a third wave cognitive-behavioral approach that incorporates mindfulness meditation and dialectics to the therapeutic process (1). DBT aims to help clients gain insight and skills to manage their thoughts, emotions, and behaviors through four skills training modules: mindfulness, interpersonal effectiveness, emotion regulation, and distress tolerance. DBT was created to treat patients with borderline personality disorder and suicidal tendencies. It assumes the lives of individuals suffering from suicidal borderline disorders are unbearable as they are currently being lived, and patients are doing the best they can in

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2016 ANNUAL MEETING POSTERS Conclusions: Dialectical Behavior Therapy (DBT) may be an effective supplemental therapy for people presenting psychological and emotional distress related to pain. Applying dialectic thinking to pain management, accepting the moment for what it is while simultaneously working toward positive change, might result in increased levels of wellbeing and pain management.

References: 1.

2.

3.

Linehan, M. DBT Skills Training Manual (second edition). New York, NY: Guilford Press; 2015.

Barrett, D. Paintracking: Your Personal Guide to Improving Life with Chronic Pain. Amherst, NY: Prometheus Books; 2012.

Linton, S. J. Applying dialectical behavior therapy to chronic pain: A case study. Scand J of Pain. 2010; 1: 50-54.

Disclosure: n/a

Blue Ribbon in Student/Fellow/Resident Embedding Palliative Care in a Cancer Center: Maximizing Pain Management Presenter: Michael Wozny, MD Authors: Michael Wozny, MD; Greg Mullinax, MD; W. Clay Jackson, MD Background: The West Cancer Center, a major provider of oncologic services to patients in the MidSouth, sought to improve the quality of pain management within their patient population, as well as to more fully integrate care. An embedded palliative care clinic was begun as a pilot program to achieve these ends.

Objective: To assess the progress of the pilot project, as well as describe plans for future innovation and research.

28

| T HE PA I N P R AC TI TI O NE R | O C T O B E R / N O V E M B E R 2 0 1 6

Methods: We conducted a review of clinical and administrative activity of the clinic, including reviewing charts and billing records from September 2014 to August 2016.

Results: We found that the clinic was highly successful in recruiting patients and elevating patient and family satisfaction (metrics pending).

We instituted protocols for automated referrals, ensured best practices for management of controlled substances, and worked to integrate various arms of the cancer center into patient care, including navigation, care support, physical therapy, nutritional support, psychologic services, and lymphedema therapy.

Conclusions: Embedded palliative care teams can be highly effective in transforming care within establishing centers of excellence in oncology, but require robust support from clinical and administrative leaders. Having proven our model is effective in episodic clinical care, we next seek to implement changes in care required by the Oncologic Care Model for a broad panel of selected patients.

References: n/a Disclosure: Dr. Jackson: Speakersâ&#x20AC;&#x2122; Bureau, Sunovion; Shareholder, Aspire Healthcare

Honorable Mentions in Original Research Improving Outcomes in Chronic Pain: Integrative Health Group Visits Presenter: Tiffiny Diers, MD Authors: Tiffiny Diers, MD; Susan McDonald, MA; Chris White, MD, JD; Sian Cotton, PhD; Nancy Elder, MD; Tony Leonard, PhD; Amy Short, MS; Jack Kues, PhD; Jill Boone, PharmD

2016 ANNUAL MEETING POSTERS

Background: Integrative health group visits (IHGV) incorporate self-management support, integrative health modalities, and medical care. While group visits and integrative modalities have been shown to improve pain-related outcomes among individuals with chronic non-malignant pain (CNMP), limited data is available on a combination approach.

IHGV conducted by an interprofessional team emphasize patient skill development and empower patients to be active participants in their own health care while encouraging social support among group members.

Support your patients between visits ORIGINAL MCKENZIE® LUMBAR ROLLS & SUPPORTS CORRECT POSTURE WHILE SITTING OR SLEEPING

Objective: To examine the effects of a monthly, six-session IHGV for individuals with CNMP in three urban primary care practices on changes in health outcomes.

Methods: Sixty-three participants with CNMP divided into two cohorts of three groups each were enrolled in two-hour-long, monthly IHGV over six months. A new integrative health modality was introduced at each visit, with an emphasis on developing skills for home practice.

Each visit included group activities and discussion and individual visits with a primary care physician. Health outcomes including pain (BPI), pain disability (PDI), anxiety (GAD- 7), patient activation (PAM), and depression (PHQ-9) were assessed pre- and post-intervention using validated instruments. Focus groups including participants, providers, staff, and support people were conducted. A Patient-Family Advisory Council guided program was implemented.

Results: Of the 63 enrolled participants, 36 (62% African American, 81% female) completed pre-post surveys at six-months. From pre- to post-six-month intervention, there were significant improvements (paired two-tailed t-test) in pain interference with enjoyment of life (P = .02), self-care (P = .02), and life support activities (P = .05).

Patient activation significantly improved (P = .003), specifically in maintaining positive lifestyle changes (P = .05). There were significant improvements in depression (P = .0002) and anxiety (P= .03).

Improvements in feeling down/hopeless (P= .04), sleep (P < .0001), tiredness (P = .001), concentration (P = .02), ability to move (P = .02), ability to relax (P = .03), restlessness (P = .05), irritability (P = .05), and fearfulness (P = .04) were also present. Focus group findings included providers expressing that this model helped them understand their patients and patients feeling more like “partners in their care” rather than “patients.”

Conclusions: IHGV may be feasible and clinically efficacious in busy academic heath practices, especially for improving mental health in CNMP patients. Both patients and providers recognized benefit from this model. Future studies should utilize larger sample sizes and assess impact of varying content and meeting frequency on pain-related outcomes to optimize dosing while minimizing logistical barriers to patients and practices.

References: n/a Disclosure: Funding: Pfizer Independent Grants for Learning & Change (IGLC) 10359049; 2013PA2.

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Outcomes Associated with a Workers Compensation Population who Participated in a Functional Restoration Program Presenter: Michael Sullivan, PT, MSPT Authors: Michelle Zenda, DPT; Mark Johnson, PhD; Michael Gates, PhD Background: Given the current common practice of administering opioids to manage pain, and the growing awareness that opioids are contraindicated for long-term chronic pain management, there is a need to increase knowledge and competency in alternative interventions. Greater competency is needed to address the psychosocial sequelae that is often comorbid with chronic pain. There is a need for a model of pain management that addresses fear of movement/pain and the necessity for movement in functional restoration.

Objective: To understand an interdisciplinary model as an alternative to traditional pharmacological treatment. Measurable Learning Objectives: 1. To gain the ability to identify key variables of diagnostic considerations that merit an interdisciplinary approach for managing chronic pain. 2. To identify appropriate pre and post assessment tools to quantify outcomes associated with functional improvement and quality of life improvement.

Methods: Pre and post assessment data was collected over an 18-month period from 158 patients who completed a six-week interdisciplinary program focused on functional restoration. Psychological measures included: Patient Health Questionnaire (PHQ-9) [Depression measure], GAD-7 [Anxiety measure], Brief Pain Inventory [Pain Intensity and Pain Interference Measures] (BPI), and the Chronic Pain Coping Inventory [Illness vs. Wellness Focused Coping] (CPCI).

Results: Paired samples statistics of pre-post mean score changes revealed that there was statistically significant improvement (P = < .001) for this population (N = 158) on all metrics except for the “pacing” and “seeking social support” behaviors in the CPCI inventory.

Conclusions: An interdisciplinary functional restoration program is an effective model of pain management. Patients demonstrated improved physical functioning including walking, strength, reduced fear of

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movement, reduced disability, improved ADL function; as well as reductions in anxiety, depression, pain intensity, pain interference; as well as decreased illness-focused coping behaviors and increased wellness-focused coping behaviors.

References: n/a

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Disclosure: n/a

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Comprehensive Inpatient Treatment for Patients with Chronic Non-Cancer Pain and Co-Occurring Substance Use Disorder

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Presenter: Peter Przekop, DO, PhD

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| T HE PA I N P R AC TI TI O NE R | O C T O B E R / N O V E M B E R 2 0 1 6

Authors: Peter Przekop, DO, PhD; Mark Haviland, PhD; Allison Przekop, DO; Keiji Oda, MPH Background: Patients with chronic non-cancer pain (CNCP) and substance use disorder (SUD) are complex and difficult to treat. Presently, there are no protocols available to guide treatment. Novel treatment approaches that have potential for successful treatment are needed. Without such efforts, these patients will become more ill and relapse.

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Objective: To evaluate a multimodal inpatient treatment program to treat patients with CNCP and SUD.

to infusion, daily one-hour sessions during the four-day infusion, and eight one-hour follow-up sessions.

Methods: Patients were enrolled in a 45-day, inpatient chronic pain program at the Betty Ford Center. Data were collected from 2013 to 2015. 122 of 150 patients who consented provided complete data.

Patients were evaluated on days 1-5, 30, and 45. The treating physician and staff were blinded to patients’ responses. Assessments were: Beck Depression Inventory-II, Brief Pain Inventory, McGill pain questionnaire, and patient portion of the West Haven-Yale Multidimensional Pain Inventory. Treatment consisted of 15 hours/week of group process and education, external and internal qigong, osteopathic manual medicine, and qigong-based mindfulness. Patients also received 20 hours per week of recovery-based SUD treatment. A mixed model analysis was used to evaluate treatment progress (above listed measures). Each mixed model included time as categorical (the three time points), age and gender as fixed effects, and patient as a random effect (randomintercept model). If the time main effect was significant (P < .05), TukeyKramer post-hoc tests were used for multiple comparisons. Results were plotted using adjusted means with 95% confidence intervals. All analyses were conducted using SAS version 9.4.

Results: Decrease in subjective pain rating by 50%; PTSD Checklist (PCL) Score decreased from 74 (severe) to 25 (subclinical); Patient was subclinical for PTSD by hospital day number three; patient no longer oxygen dependent. Patient maintained results for two years.

Results: Results were consistently similar across all measures (total and subscale scores). Patients showed marked improvement in depression and pain ratings, and these improvements were robust and statistically significant.

Conclusions: This case provides preliminary support for use of ketamine and psychotherapy yielding rapid reduction in PTSD and chronic pain symptom severity. These findings may lead to additional novel approaches to combining pharmacologic and psychotherapeutic treatments for patients with this co-occurring condition.

References: 1.

2.

3.

Sigtermans MJ, van Hilten JJ, Bauer MC, et al. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. 2009;145(3):304-311.

Feder A, Parides MK, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial.

JAMA Psychiatry. 2014;71(6):681-68.

Foa EB, Keane TM, Friedman MJ, Cohen JA. Effective Treatments for PTSD: Practice Guidelines from the International Society for Traumatic Stress Studies. 2nd ed. New York:Guilford Press; 2008.

Disclosure: n/a

Conclusions: The findings are sufficiently encouraging to warrant further evaluation of the protocol and to plan both comparative studies and studies beyond patients’ 45-day inpatient stay.

References: n/a Disclosure: n/a

Ketamine and Psychotherapy for CRPS/PTSD: A Two-year Follow-up.

Presenter: Benjamin Keizer, PhD Authors: Benjamin Keizer, PhD; Justin Boge, DO Background: Intravenous infusion of ketamine hydrochloride has been demonstrated as effective for treating various chronic pain syndromes, especially CRPS (1). Recently ketamine infusion has shown to be a potential treatment for posttraumatic stress disorder (2). The current gold standard for treating PTSD is psychotherapy (3). We report physical and psychological measures for a treatment that combines psychotherapy with a ketamine infusion for a patient with co-occurring chronic pain and PTSD.

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Objective: To present a case study for a patient who received this treatment with a two-year follow-up.

Methods: A 33-year-old female with past medical history significant for left lower extremity CRPS, Reynaud’s syndrome, bronchiectasis with right upper lobectomy (oxygen dependent since 2008), and PTSD secondary to late adolescent sexual assault. Patient completed 14-day taper off 75 mcg/hr/72 hrs fentanyl patch and oral hydromorphone (32 mg daily dose) prior to infusion. Medical management consisted of continuous subanesthetic ketamine infusion. Psychiatric treatment consisted of a one-hour evidence-based psychotherapy session prior

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