The Pain Practitioner - Winter 2015

american academy of pain management

No Life Limited by Pain

The P Pain ain Pr Practitioner Winter 2015

No Life Limited By Pain 2015 THE 26TH ANNUAL MEETING

INSIDE: 2015 Annual Meeting Review, Blue Ribbon Poster Abstract Winners, Autologous Stem Cell Therapy, and more!

Get things moving with reliable and rapid relief.

RELISTOR helps provide chronic non-cancer pain patients relief from opioid-induced constipation— without compromising analgesia.1,2 • 6 out of 10 RELISTOR® (methylnaltrexone bromide) patients (n=150) had at least 3 Spontaneous Bowel Movements (SBMs) per week (P<0.001)1,2 • One-third of patients taking RELISTOR (n=150) experienced an SBM within 4 hours of their first dose (P<0.001)1 IndIcatIons RELISTOR is indicated for the treatment of opioid-induced constipation in adult patients with chronic non-cancer pain.

RELISTOR is indicated for the treatment of opioid-induced constipation in adult patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Use of RELISTOR beyond four months has not been studied.

conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom.

If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their physician.

Symptoms consistent with opioid withdrawal, Important safety InformatIon including hyperhidrosis, chills, diarrhea, RELISTOR® (methylnaltrexone bromide) abdominal pain, anxiety, and yawning have Subcutaneous Injection is contraindicated in patients with known or suspected gastrointestinal occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain obstruction and patients at increased risk of barrier may be at increased risk for opioid recurrent obstruction, due to the potential for withdrawal and/or reduced analgesia and gastrointestinal perforation. should be monitored for adequacy of analgesia Cases of gastrointestinal perforation have been and symptoms of opioid withdrawal. reported in adult patients with opioid-induced constipation and advanced illness with conditions Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for that may be associated with localized or diffuse additive effects of opioid receptor antagonism reduction of structural integrity in the wall of and increased risk of opioid withdrawal. the gastrointestinal tract (e.g., peptic ulcer RELISTOR may precipitate opioid withdrawal in disease, Ogilvie’s syndrome, diverticular disease, a fetus and should be used during pregnancy infiltrative gastrointestinal tract malignancies only if the potential benefit justifies the potential or peritoneal metastases). Take into account the risk to the fetus. In nursing mothers, a decision overall risk-benefit profile when using RELISTOR should be made to discontinue nursing or in patients with these conditions or other

discontinue the drug, taking into account the importance of the drug to the mother.

In the clinical study in adult patients with opioid-induced constipation and chronic non-cancer pain, the most common adverse reactions (≥ 1%) were abdominal pain, nausea, diarrhea, hyperhidrosis, hot flush, tremor, and chills.

In clinical studies in adult patients with opioid-induced constipation and advanced illness, the most common adverse reactions (≥ 5%) were abdominal pain, flatulence, nausea, dizziness, and diarrhea.

Please see Brief Summary of full Prescribing Information for RELISTOR on the adjacent page. references 1. Michna E, Blonsky ER, Schulman S, et al. Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with chronic nonmalignant pain: a randomized controlled study. J Pain. 2011;12(5):554-562.

2. RELISTOR® (methylnaltrexone bromide) Prescribing Information, Salix Pharmaceuticals, Inc.

Product under license from Manufactured for: Salix Pharmaceuticals, a division of Valeant Pharmaceuticals North America LLC 8510 Colonnade Center Drive, Raleigh, NC 27615 For additional information, call: 1-866-669-SLXP (7597) To report adverse events, call: 1-800-508-0024 RELISTOR is a trademark of Valeant Pharmaceuticals International, Inc. or its affiliates.

All other product/brand names are trademarks of their respective owners. ©2015 Valeant Pharmaceuticals North America LLC. All rights reserved.

Printed in USA. REL-US-0152 v.1 www.salix.com

The following is a brief summary only; see full Prescribing Information for complete product information.

INDICATIONS AND USAGE Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain RELISTOR is indicated for the treatment of opioid-induced constipation in adult patients with chronic non-cancer pain.

Opioid-Induced Constipation in Adult Patients with Advanced Illness RELISTOR is indicated for the treatment of opioid-induced constipation in adult patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient.

Limitation of use: Use of RELISTOR beyond four months has not been studied in the advanced illness population.

CONTRAINDICATIONS RELISTOR is contraindicated in patients with known or suspected gastrointestinal obstruction and patients at risk of recurrent obstruction, due to the potential for gastrointestinal perforation.

WARNINGS AND PRECAUTIONS Gastrointestinal Perforation Cases of gastrointestinal perforation have been reported in adult patients with opioid-induced constipation and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom.

Severe or Persistent Diarrhea If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.

Opioid Withdrawal Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia. Take into account the overall risk-benefit profile when using RELISTOR in such patients. Monitor for adequacy of analgesia and symptoms of opioid withdrawal in such patients.

ADVERSE REACTIONS 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 clinical practice.

Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain The safety of RELISTOR was evaluated in a double-blind, placebo-controlled trial in adult patients with opioid-induced constipation and chronic non-cancer pain receiving opioid analgesia.

This study (Study 1) included a 4-week, double-blind, placebo controlled period in which adult patients were randomized to receive RELISTOR 12 mg once daily (150 patients) or placebo (162 patients).

After 4 weeks of double-blind treatment, patients began an 8-week open-label treatment period during which RELISTOR 12 mg was administered less frequently than the recommended dosage regimen of 12 mg once daily.

Adverse reactions in adult patients with opioid-induced constipation and chronic non-cancer pain receiving RELISTOR are shown in the following table. The adverse reactions in the table below may reflect symptoms of opioid withdrawal.

Adverse Reactions* in 4-Week Double-Blind, PlaceboControlled Period of Clinical Study of RELISTOR in Adult Patients with Opioid-Induced Constipation and Chronic Non-Cancer Pain RELISTOR Placebo 12 mg once daily n = 162 n = 150 Abdominal Pain 21% 6% Nausea 9% 6% Diarrhea 6% 4% Hyperhidrosis 6% 1% Hot Flush 3% 2% Tremor 1% < 1% Chills 1% 0% * Adverse reactions occurring in ≥ 1 % of patients receiving RELISTOR 12 mg once daily and at an incidence greater than placebo.

During the 4-week double-blind period, in patients with opioid-induced constipation and chronic non-cancer pain that received RELISTOR 12 mg every other day, there was a higher incidence of adverse reactions, including nausea (12%), diarrhea (12%), vomiting (7%), tremor (3%), feeling of body temperature Adverse Reaction

change (3%), piloerection (3%), and chills (2%) as compared to daily RELISTOR dosing. Use of RELISTOR 12 mg every other day is not recommended in patients with OIC and chronic non-cancer pain. The rates of discontinuation due to adverse reactions during the double-blind period (Study 1) were higher in the RELISTOR once daily (7%) than the placebo group (3%). Abdominal pain was the most common adverse reaction resulting in discontinuation from the double-blind period in the RELISTOR once daily group (2%).

The safety of RELISTOR was also evaluated in a 48-week, open-label, uncontrolled trial in 1034 adult patients with opioid-induced constipation and chronic non-cancer pain (Study 2).

Patients were allowed to administer RELISTOR 12 mg less frequently than the recommended dosage regimen of 12 mg once daily, and took a median of 6 doses per week. A total of 624 patients (60%) completed at least 24 weeks of treatment and 477 (46%) completed the 48-week study. The adverse reactions seen in this study were similar to those observed during the 4-week double-blind period of Study 1. Additionally, in Study 2, investigators reported 4 myocardial infarctions (1 fatal), 1 stroke (fatal), 1 fatal cardiac arrest and 1 sudden death. It is not possible to establish a relationship between these events and RELISTOR. Opioid-Induced Constipation in Adult Patients with Advanced Illness The safety of RELISTOR was evaluated in two, double-blind, placebo-controlled trials in adult patients with opioid-induced constipation and advanced illness receiving palliative care: Study 3 included a single dose, double blind, placebo-controlled period, whereas Study 4 included a 14-day multiple dose, double-blind, placebo-controlled period.

The most common (≥5%) adverse reactions in adult patients with opioid-induced constipation and advanced illness receiving RELISTOR are shown in the following table.

Adverse Reactions from all Doses in Double-Blind, PlaceboControlled Clinical Studies of RELISTOR in Adult Patients with Opioid-Induced Constipation and Advanced Illness* Adverse RELISTOR Placebo Reaction n = 165 n = 123 Abdominal Pain 29% 10% Flatulence 13% 6% Nausea 12% 5% Dizziness 7% 2% Diarrhea 6% 2% * Adverse reactions occurring in ≥ 5 % of patients receiving all doses of RELISTOR (0.075, 0.15, and 0.30 mg/kg/dose) and at an incidence greater than placebo.

The rates of discontinuation due to adverse events during the double-blind placebo controlled clinical trials (Study 3 and Study 4) were comparable between RELISTOR (1%) and placebo (2%).

Postmarketing Experience The following adverse reactions have been identified during post-approval use of RELISTOR. Because they 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.

Gastrointestinal Perforation, cramping, vomiting General Disorders and Administrative Site Disorders Diaphoresis, flushing, malaise, pain. Cases of opioid withdrawal have been reported.

DRUG INTERACTIONS Other Opioid Antagonists Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.

Drugs Metabolized by Cytochrome P450 Isozymes In healthy subjects, a subcutaneous dose of 0.30 mg/kg of methylnaltrexone did not significantly affect the metabolism of dextromethorphan, a CYP2D6 substrate.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C There are no adequate and well-controlled studies with RELISTOR in pregnant women. The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood brain barrier. In animal reproduction studies, no effects on embryo-fetal development were observed with the administration of intravenous methylnaltrexone during organogenesis in rats and rabbits at doses up to 20 times and 26 times, respectively, the maximum recommended human dose (MRHD) of 0.2 mg/kg/day.

RELISTOR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers It is not known whether RELISTOR is present in human milk.

However, methylnaltrexone bromide is present in rat milk. Because of the potential for serious adverse reactions, including opioid withdrawal, in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use Safety and effectiveness of RELISTOR have not been established in pediatric patients.

In juvenile rats administered intravenous methylnaltrexone bromide for 13 weeks, adverse clinical signs such as convulsions,

tremors and labored breathing were observed, and the juvenile rats were found to be more sensitive to the adverse effects of methylnaltrexone bromide when compared to adult animals.

Juvenile dogs administered intravenous methylnaltrexone bromide for 13 weeks had a toxicity profile similar to adult dogs.

Geriatric Use In the double-blind studies, a total of 118 (14%) patients aged 65-74 years (79 methylnaltrexone bromide, 39 placebo) and a total of 108 (13%) patients aged 75 years or older (64 methylnaltrexone bromide, 44 placebo) were enrolled. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Based on pharmacokinetic data, and safety and efficacy data from controlled clinical trials, no dose adjustment based on age is recommended.

Renal Impairment No dose adjustment is required in patients with mild or moderate renal impairment. Dose reduction by one-half is recommended in patients with severe renal impairment (creatinine clearance less than 30 mL/min as estimated by Cockcroft-Gault).

Hepatic Impairment No dose adjustment is required for patients with mild or moderate hepatic impairment.

OVERDOSAGE A study of healthy volunteers noted orthostatic hypotension associated with a dose of 0.64 mg/kg administered as an intravenous bolus. Monitor for signs or symptoms of orthostatic hypotension and initiate treatment as appropriate.

If a patient on opioid therapy receives an overdose of RELISTOR, the patient should be monitored closely for potential evidence of opioid withdrawal symptoms such as chills, rhinorrhea, diaphoresis or reversal of central analgesic effect. Base treatment on the degree of opioid withdrawal symptoms, including changes in blood pressure and heart rate, and on the need for analgesia.

PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Administration Advise all patients to: • Inject RELISTOR subcutaneously in the upper arm, abdomen or thigh. Do not inject at the same spot each time (rotate injection sites).

• Safely dispose of needles by following the sharps disposal recommendations described in the RELISTOR Instructions for Use. • Be within close proximity to toilet facilities once RELISTOR is administered.

• Discontinue RELISTOR if treatment with the opioid pain medication is also discontinued.

Advise chronic non-cancer pain patients receiving RELISTOR for opioid-induced constipation to: • Discontinue all maintenance laxative therapy prior to initiation of RELISTOR. Laxative(s) can be used as needed if there is a suboptimal response to RELISTOR after three days.

• Inject one dose every day.

• Inform their healthcare provider if their opioid regimen is changed, to avoid adverse reactions, such as diarrhea.

Advise patients with advanced illness receiving RELISTOR for opioid-induced constipation to: • Inject one dose every other day, as needed, but no more frequently than one dose in a 24-hour period.

Gastrointestinal Perforation Advise patients to discontinue RELISTOR and to promptly seek medical attention if they develop unusually severe, persistent, or worsening abdominal pain.

Severe or Persistent Diarrhea Advise patients to discontinue RELISTOR if they experience severe or persistent diarrhea.

Opioid Withdrawal Advise patients that symptoms consistent with opioid withdrawal may occur while taking RELISTOR, including sweating, chills, diarrhea, abdominal pain, anxiety, and yawning.

Pregnancy Advise females of reproductive potential, who become pregnant or are planning to become pregnant that the use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the undeveloped blood brain barrier.

Nursing Advise females who are nursing against breastfeeding during treatment with RELISTOR due to the potential for opioid withdrawal in nursing infants.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

To report adverse events, a product complaint, or for additional information, call: 1-800-508-0024.

Manufactured for: Under License from:

Salix Pharmaceuticals, Inc. Raleigh, NC 27615

Progenics Pharmaceuticals, Inc. Tarrytown, NY 10591

REL-RALAB56-102014

No Life Limited by Pain

The Pain Practitioner WINTER 2015, VolumE 25, NumbER 4

Notes from the Field 4

Politics and Pain: Strange Bedfellows or Untapped Opportunity?

By Robert Twillman, PhD, FAPM, Executive Director

Academy News 6 14

Newly Credentialed Members You Should Know...

American Academy of Pain Management www.aapainmanage.org

ACADEMY BOARD OF DIRECTORS President Joanna Katzman, mD, mSPH Past President Robert A. bonakdar, mD, FAAFP Secretary Paul Christo, mD, mbA Treasurer Kevin T. Galloway, bSN, mHA, Colonel, uS Army (Retired) Directors-at-Large Alfred V. Anderson, mD, DC John Garzione, DPT Christian D. GonzĂĄlez, mD Gerald Q. Greenfield, Jr., mD W. Clay Jackson, mD, DipTh michael Kurisu, Do, AbIHm Arthur S. Roberts, DDS, mD Liaison to the Board maggie buckley Executive Director Emeritus and Director of Board Development lennie Duensing, mEd

ACADEMY STAFF AND CONSULTANTS

Features 16

No Life Limited by Pain 2015 The 26th Annual Meeting:

More Answers But Yet So Many Questions

By Christine Rhodes, MS

24

No Life Limited by Pain 2015 The 26th Annual Meeting:

Blue Ribbon Poster Abstracts

By Forest Tennant MD, DrPH and Bruce F. Singer, PsyD

36

No Life Limited by Pain 2015 The 26th Annual Meeting:

ACPP Update: New Clinical Skills Cohort Model a Success

By Lou Clark, MFA, PhD

From the Clinic 40 Autologous Stem Cell Therapy:

A Naturopathic Approach for the Treatment of Chronic Musculoskeletal Painâ&#x20AC;&#x201D;Part II of II

By Harry Adelson, ND

Commentary 44 Modulating Pain Signal Transmission:

How Targeted Nervous System Regulation Can Manage Pain without Side Effects

By Peter Behel, MA, BCB

Subscribe to The Pain Practitioner!

If you are not a member, you can still get this quarterly publication for just $50/year. Send your check to the American Academy of Pain Management, 975 morning Star Drive, Ste. A, Sonora, CA 95370

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Executive Director Robert Twillman, PhD, FAPm Director of Education and Credentialing Debra Nelson-Hogan Director of Sales, Marketing and Events Jillian manley Director of the State Pain Policy Advocacy Network (SPPAN) Amy Goldstein, mSW Researcher and Policy Analyst Katie Duensing, JD Credentialing Account Manager macKenzie Davis Website and Database Director Eric blosch Account Managers Rosemary lemay, Staci Criswell, and Sheila miller Accounting Director Kristin Taylor Education Manager Cathleen Coneghen Office Manager Karen Hebert

THE PAIN PRACTITIONER STAFF AND CONSULTANTS Editor-in-Chief Debra Nelson-Hogan Advertising and Sales Jillian manley, Sheila miller Managing Editor Cathleen Coneghen Clinical Editor Christine Rhodes, mS Art Director Amy bothwell Copy Editor Rosemary Hope The Pain Practitioner is published by the American Academy of Pain Management, 975 Morning Star Drive, Ste., A, Sonora, CA 95370, Phone 209-533-9744, Fax 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 Nelson-Hogan at dhogan@aapainmanage. org. Contact Sheila Miller at 209-533-9744 regarding advertising opportunities, media kits, and prices.

The Pain Practitioner is published by the American Academy of 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 American Academy of 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

Politics and Pain: Strange Bedfellows or Untapped Opportunity?

BY ROBERT T WILL M A N, PHD, FAPM, E XECU TI V E DIREC TOR

A

s the United States kicks off another presidential election year, I’ve been thinking quite a bit about how the pain care community might take advantage of the opportunity to advocate for a well-reasoned political agenda boosting integrative pain care.

Politicians are notorious for pandering to constituencies that can bring them the most votes, and aside from the broadest categories (e.g., groups based on gender, ethnicity, etc.), it would be hard to argue that people with pain, and those who care for them, could represent an enormous bloc of voters in 2016. After all, with statistics like the Institute of Medicine’s 100 million+ adults with chronic pain, and more recent studies showing 25-30 million Americans who experience chronic pain daily or nearly daily, not to mention their significant others and professional caregivers, it’s apparent that this bloc could even represent the majority of voters in the next presidential election.

What are the candidates saying about pain care? Well, so far, very little that is positive, and some that is negative.

Most candidates have made at least some attempt to establish general positions on resolving the “epidemic” of prescription drug abuse. In this vein, several have touted plans for increased access to medication-assisted treatment for opioid use disorders. Some, most notably Hillary Clinton, have decried the FDA’s recent approval of a labeling change for OxyContin (indicating it is safe and effective for use by people with pain in the 11- to 18- year-old range), without acknowledging that some adolescents really do have chronic pain that responds well to opioids. What is missing, though, is any discussion about increasing access to non-pharmaceutical treatments for pain. This gives us an opening to raise our voices and leverage the size of our voting bloc to further the Academy’s mission of expanding access to integrative pain care.

With all the concern about prescription drug abuse, candidates at all levels will need to propose fixes for the problem.

Undoubtedly, most of those fixes will focus on increasing access to substance abuse treatment and decreasing opioid prescribing. Those are the obvious, simple solutions, so those are the solutions that candidates will reach for. It is our obligation, on behalf of the people with pain for whom we care, to raise our hands and to ask what these candidates intend to do for people with pain as they take away one of their treatments.

Don’t get me wrong—I know that there are many people with pain who are prescribed opioids for painful conditions that don’t respond to them, and who are prescribed doses that far

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exceed the bounds of what is both safe and effective. But the fact remains that they are being prescribed opioids because their pain care clinicians recognize that they still have pain.

Take away the opioids, and the pain remains—and may be worse for some. What do candidates propose to substitute for the opioids, so that people with pain can improve their levels of functioning and/or reduce their levels of pain?

We need to be speaking up now to ensure that integrative approaches to pain care become part of the plans developed by candidates. How do we do that? We do that by assertively reaching out to local campaign representatives for national candidates, and by reaching out to local offices representing campaigns for statewide and local candidates. We do that by personally contacting candidates whenever possible, especially those who are most accessible, namely, those running for state legislatures. We go to town hall meetings for candidates, stand up, and ask them what they propose to do for the one-third of their constituents who have chronic pain. When they fumble for an answer, we offer to help them out by suggesting that they work with us to increase access to nonpharmacological treatments for pain. And we keep asking the questions until we get an acceptable answer.

People in this country are, by all apparent measures, frustrated and disgusted with the current state of the political process, and many want to respond by avoiding the whole mess. I think there are parallels between politics and health care that instruct us on the necessity to intervene strongly and quickly. The political process has developed what appears to be a chronic illness that leads to large-scale dysfunction, and we know from experience that allowing those kinds of problems to fester further will only create more dysfunction and distress. It’s time for us to step in with an intervention that moves toward restoring health—an intervention that, in the best traditions of integrative medicine, aims not just to eliminate a pathogenic process, but to enhance a salutogenic process. That intervention is to tell candidates what we want and need in order to address both of the public health crises we encounter daily.

It’s at times like these that I am reminded of an admonition I’ve heard many times: If you’re not at the table, you’re on the menu. That’s clearly true in this context, so let’s demand our seat at the table!

No Life Limited By Pain 2016 THE 27TH ANNUAL MEETING

San Antonio, TTexas exas SEPTEMBER 22-25, 2016

J W M A R R I O T T H I L L C O U N T RY

Join clinicians from from a wide variety of disciplines, to exchange ideas and expand your knowledge!

This meeting is for all clinicians interested interested in learning lear ning about an integrative approach approach to pain management.

REGISTER NOW at aapainmanage.or aapainmanage .org g or call (209) 533-9744

MAKE YOUR PLANS FOR 2016!

Register early for reduced pricing.

@aapainmanage #NoLifeLimitedByPain facebook/aapainmanage

5 REASONS TO ATTEND...

1. Learn about the best practices in integrative pain management.

2. Participate in handson and experiential sessions.

3. Connect with thought leaders, researchers, and like-minded clinicians.

4. Get updates on new technologies and techniques in pain management.

5. Find out about state and federal policies that may affect your practice.

ACADEMY NE WS

Newly Credentialed Members Open to all pain practitioners, the Academy’s Credential demonstrates that a clinician is knowledgeable about interdisciplinary/integrative pain management; has practiced in the field of pain management for at least two years; remains in good standing with federal and state regulatory agencies; has passed a rigorous exam; and is committed to ongoing education in the field of pain. The Academy welcomes the following credentialed pain practitioners who have met the Academy’s requirements and demonstrated proficiency in the management of pain.

AdvAnced cRedenTIALed PAIn PRAcTITIOneR (AcPP) Advanced diplomate Y. Lauren devoe, Md, is working at Advanced Pain Specialists of Tulsa, Oklahoma. She received her medical degree from The Queen’s University of Belfast, UK. She is board-certified in ophthalmology (FRCOphth, UK) and family medicine (ABFM, US). She is now in full-time pain management.

collins egbujuo, Md, is a family physician with a keen

interest in pain management. He is currently working with Prince Albert Parkland Health Region in Saskatchewan, Canada. His memberships include the Canadian Association of Nigerian Physicians and Dentists, SMA, the Canadian Medical Association, and the College of Family Physicians of Canada.

Henry G. dela Torre, Md, obtained his de-

gree from the Cebu Institute of Medicine, Cebu City, Philippines, in 1973. In 2002, he completed acupuncture training through the University of Los Angeles-Helms Medical Institute. He is actively practicing in DuBois, Pennsylvania, in general medicine, acupuncture, detoxification, and pain management while he visits nursing homes and schools.

Bruce Mccrea, dc, FnP, dAAPM, has com-

bined medicine, chiropractic, acupuncture, therapy, rehab, massage, traction, and nutrition for pain relief and family medicine for more than 25 years.

Barry d. Glasser, Md, is board certified

in internal medicine at Medical One in Brigantine, New Jersey. He is the medical director at John Brooks Recovery Center.

He is a member of the Medical Society of New Jersey and fellow of the American Board of Addiction Medicine. He is currently enrolled in acupuncture courses at Harvard Medical School.

GeneRAL cRedenTIALed PAIn PRAcTITIOneR (GcPP) diplomate Bradley A. Urie, Md, completed his anes-

thesiology residency training at Detroit Medical Center/Wayne State University.

He completed his pain fellowship in Buffalo, New York, under the tutelage of Oscar A. De Leon Casasola, MD, president of the American Society of Regional Anesthesia and Pain Medicine. Dr. Urie has been treating pain exclusively for seven years and has opened his own pain clinic, Pinnacle Pain Management, in Layton, Utah.

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Fellow Karen Beabout, PA, graduated from the physician assistant program at Louisiana State University Health Sciences Center in 2010 after serving in the US Air Force. She has spent four years working in interventional pain management and is a strong advocate for utilizing a multidisciplinary approach in treating patients with chronic pain. She finds it very gratifying and counts it a privilege to work in a field that offers help to patients with such a desperate need. In her spare time she enjoys cycling and long-distance running.

clinical Associate Stephanie Bourque, dPh, has been a licensed pharmacist

for 21 years. She is a clinical staff pharmacist at Williamson Medical Center in Franklin, Tennessee, where she is part of the palliative care team. She also collects, monitors, and reports adverse drug reactions to the pharmacy and therapeutics committee on a quarterly basis.

ACADEMY NE WS

Thank you to our Corporate Council Members!

American Academy of Pain Management Corporate CounCil MeMbership Contact sheila Miller (smiller@aapainmanage.org) or Jillian Manley (jmanley@aapainmanage.org) (209) 533-9744 to become a Corporate Council Member today!

Announcing

our new online

PA P Ain cA cAre le eA Arning center – Free F For or MeMbers!

Me bers!

accredited education. anytime you want. whenever you want.

The Academy’s new online learning management center provides on-going education for those caring for people with chronic pain. All programs are accredited for continuing education and include: • Audiovisual presentations from leading experts in the field of pain management.

• Written educational activities that are theoretical and practical.

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• The ability to print your accreditation certificate and access your continuing education history at any time.

Go to education.aapainmanaGe.orG to Get started today!

T H E PA I N P R AC T I T I O N E R

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HYSINGLAâ&#x201E;˘ ER:

The first and only once-daily hydrocodone with abuse-deterrent properties and no acetaminophen acetaminophen

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; AND CYTOCHROME P450 3A4 INTERACTION Addiction, Abuse, and Misuse HYSINGLA ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patientâ&#x20AC;&#x2122;s risk prior to prescribing HYSINGLA 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 HYSINGLA ER. Monitor for respiratory depression, especially during initiation of HYSINGLA ER or following a dose increase.

Instruct patients to swallow HYSINGLA ER tablets whole; crushing, chewing, or dissolving HYSINGLA ER tablets can cause rapid release and absorption of a potentially fatal dose of hydrocodone [see Warnings and Precautions (5.2)].

Accidental Ingestion Accidental ingestion of even one dose of HYSINGLA ER, especially by children, can result in

a fatal overdose of hydrocodone [see Warnings and Precautions (5.2)].

Neonatal Opioid Withdrawal Syndrome Prolonged use of HYSINGLA 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 HYSINGLA ER with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone 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 hydrocodone plasma concentration.

Monitor patients receiving HYSINGLA ER and any CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.11), Drug Interactions (7.1), and Clinical Pharmacology (12.3)].

Please see Additional Warnings and Precautions on the following pages.

Please read Brief Summary of Full Prescribing Information on the following pages, including Boxed Warning.

Hysingla ER: The same opioid molecule your hydrocodone patients are familiar with

• •

One tablet daily provides 24 hours of hydrocodone delivery Formulated with properties intended to make the tablet more difficult to misuse and abuse – The in vitro data demonstrate that Hysingla ER has physical and chemical properties that are expected to deter intranasal and intravenous abuse. The data from the clinical abuse potential studies, along with support from the in vitro data, also indicate that Hysingla ER has physicochemical properties that are expected to reduce intranasal abuse and oral abuse when chewed – However, abuse of Hysingla ER by the intravenous, intranasal, and oral routes is still possible

• • •

– With parenteral abuse, the inactive ingredients in Hysingla ER can result in death, local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury Proven effective in a clinical trial Contains no acetaminophen Flexibility of 7 dosage strengths: 20, 30, 40, 60, 80, 100, and 120 mg tablets – The starting dose for patients who are not opioid tolerant is Hysingla ER 20 mg orally every 24 hours.

Opioid-tolerant patients are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid. Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression

INDICATIONS AND USAGE Hysingla ER (hydrocodone bitartrate) 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 Hysingla 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.

• Hysingla ER is not indicated as an as-needed analgesic.

CONTRAINDICATIONS • Hysingla ER is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment, known or suspected paralytic ileus and gastrointestinal obstruction, hypersensitivity to any component of Hysingla ER or the active ingredient, hydrocodone bitartrate.

WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse • Hysingla ER contains hydrocodone, a Schedule II controlled substance. Hysingla ER exposes users to the risks of opioid addiction, abuse, and misuse.

As extended-release products such as Hysingla 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 hydrocodone present. Addiction can occur at recommended doses and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing

For more information, visit HysinglaER.com

Hysingla ER, and monitor all patients during therapy for the development of these behaviors or conditions.

Abuse or misuse of Hysingla ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the hydrocodone and can result in overdose and death.

Dosage and Administration • Hysingla ER tablets must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth.

Crushing, chewing, or dissolving Hysingla ER tablets will result in uncontrolled delivery of hydrocodone and can lead to overdose or death.

Titration and Maintenance of Therapy • Continually re-evaluate patients receiving Hysingla ER to assess the maintenance of pain control and the relative incidence of adverse reactions as well as monitoring for the development of addiction, abuse, or misuse.

hydrocodone reengineered

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

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

Interactions with Central Nervous System Depressants • Hypotension, profound sedation, coma, respiratory depression, or death may result if Hysingla ER is used concomitantly with other CNS depressants, including alcohol or illicit drugs that can cause CNS depression.

Start with a lower Hysingla ER dose than usual (i.e., 20-30% less), monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant.

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

Use in Patients with Head Injury and Increased Intracranial Pressure • Monitor patients closely who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or impaired consciousness). Opioids may obscure the clinical course in a patient with a head injury. Avoid the use of Hysingla ER in patients with impaired consciousness or coma.

Hypotensive Effect • Hysingla ER may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. Monitor patients during dose initiation or titration. In patients with circulatory shock, Hysingla ER

may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of Hysingla ER in patients with circulatory shock.

Gastrointestinal Obstruction, Dysphagia, and Choking • Use caution when prescribing Hysingla ER for patients who have difficulty swallowing, or have underlying gastrointestinal disorders that may predispose them to obstruction, dysphagia, or choking. Consider use of an alternative analgesic in these patients.

Decreased Bowel Motility • Hysingla ER is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus.

Monitor for decreased bowel motility in post-operative patients receiving opioids. The administration of Hysingla ER may obscure the diagnosis or clinical course in patients with acute abdominal conditions.

Hydrocodone may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis.

Cytochrome P450 3A4 Inhibitors and Inducers • Concomitant use of CYP3A4 inhibitors may prolong opioid effects. Use with CYP3A4 inducers may cause lack of efficacy or development of withdrawal symptoms. If co-administration is necessary, evaluate patients frequently and consider dose adjustments until stable drug effects are achieved.

Driving and Operating Machinery • Hysingla ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.

Interaction with Mixed Agonist/Antagonist Opioid Analgesics • Avoid the use of mixed agonist/antagonist analgesics in patients who have received or are receiving Hysingla ER, as they may reduce the analgesic effect and/or precipitate withdrawal.

QTc Interval Prolongation • QTc prolongation has been observed following daily doses of 160 mg of Hysingla ER. Avoid use in patients with congenital QTc syndrome. This observation should be considered in making clinical decisions regarding patient monitoring when prescribing Hysingla ER in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that are known to prolong QTc interval. In patients who develop QTc prolongation, consider reducing the dose.

ADVERSE REACTIONS • Most common treatment-emergent adverse reactions (≥5%) reported by patients treated with Hysingla ER in the clinical trials were constipation, nausea, vomiting, fatigue, upper respiratory tract infection, dizziness, headache, and somnolence.

Please see Additional Warnings and Precautions on the preceding pages.

Please read Brief Summary of Full Prescribing Information on the following pages, including Boxed Warning.

©2015 Purdue Pharma L.P., Stamford, CT 06901-3431 B9935-A 4/15

BRIEF SUMMARY OF PRESCRIBING INFORMATION (For complete details please see the Full Prescribing Information and Medication Guide.)

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFETHREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; AND CYTOCHROME P450 3A4 INTERACTION Addiction, Abuse, and Misuse HYSINGLA™ 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 HYSINGLA 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 HYSINGLA ER. Monitor for respiratory depression, especially during initiation of HYSINGLA ER or following a dose increase. Instruct patients to swallow HYSINGLA ER tablets whole; crushing, chewing, or dissolving HYSINGLA ER tablets can cause rapid release and absorption of a potentially fatal dose of hydrocodone [see Warnings and Precautions (5.2)].

Accidental Ingestion Accidental ingestion of even one dose of HYSINGLA ER, especially by children, can result in a fatal overdose of hydrocodone [see Warnings and Precautions (5.2)].

Neonatal Opioid Withdrawal Syndrome Prolonged use of HYSINGLA 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 HYSINGLA ER with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone 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 hydrocodone plasma concentration. Monitor patients receiving HYSINGLA ER and any CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.11), Drug Interactions (7.1), and Clinical Pharmacology (12.3)].

4 CONTRAINDICATIONS HYSINGLA ER is contraindicated in patients with: • Significant respiratory depression • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment • Known or suspected paralytic ileus and gastrointestinal obstruction • Hypersensitivity to any component of HYSINGLA ER or the active ingredient, hydrocodone bitartrate 5 WARNINGS AND PRECAUTIONS 5.1 Addiction, Abuse, and Misuse HYSINGLA ER contains hydrocodone, a Schedule II controlled substance.

As an opioid, HYSINGLA ER exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9.1)]. As extended-release products such as HYSINGLA 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 hydrocodone present. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed HYSINGLA ER and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing HYSINGLA ER, and monitor all patients receiving HYSINGLA ER for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol addiction or abuse) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the prescribing of HYSINGLA ER for the proper management of pain in any given patient. Abuse or misuse of HYSINGLA ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the hydrocodone and can result in overdose and death [see Drug Abuse and Dependence (9.1), and Overdosage (10)]. Opioid agonists are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing HYSINGLA 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 modified-release opioids, even when used as recommended. Respiratory depression from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death.

Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10.2)]. 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 HYSINGLA ER, the risk is greatest during the initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with HYSINGLA ER and following dose increases. To reduce the risk of respiratory depression, proper dosing and titration of HYSINGLA ER are essential [see Dosage and Administration (2.1, 2.2)]. Overestimating the HYSINGLA ER dose when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental ingestion of even one dose of HYSINGLA ER, especially by children, can result in respiratory depression and death due to an overdose of hydrocodone.

5.3 Neonatal Opioid Withdrawal Syndrome Prolonged use of HYSINGLA 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 requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight.

The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.

5.4 Interactions with Central Nervous System Depressants Hypotension, profound sedation, coma, respiratory depression, and death may result if HYSINGLA ER is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of HYSINGLA ER in a patient taking a CNS depressant, assess the duration 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 HYSINGLA ER is made, start with a lower HYSINGLA ER dose than usual (i.e., 20-30% less), monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant [see Drug Interactions (7.2)]. 5.5 Use in Elderly, Cachectic, and Debilitated Patients Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Monitor such patients closely, particularly when initiating and titrating HYSINGLA ER and when HYSINGLA ER is given concomitantly with other drugs that depress respiration [see Warnings and Precautions (5.2)]. 5.6 Use in Patients with Chronic Pulmonary Disease Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression for respiratory depression, particularly when initiating therapy and titrating with HYSINGLA ER, as in these patients, even usual therapeutic doses of HYSINGLA ER may decrease respiratory drive to the point of apnea [see Warnings and Precautions (5.2)]. Consider the use of alternative non-opioid analgesics in these patients if possible. 5.7 Use in Patients with Head Injury and Increased Intracranial Pressure In the presence of head injury, intracranial lesions or a preexisting increase in intracranial pressure, the possible respiratory depressant effects of opioid analgesics and their potential to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO2 retention) may be markedly exaggerated. Furthermore, opioid analgesics can produce effects on pupillary response and consciousness, which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries. Monitor patients closely who may be susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of a patient with a head injury. Avoid the use of HYSINGLA ER in patients with impaired consciousness or coma. 5.8 Hypotensive Effect HYSINGLA ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an added risk to individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone. Monitor these patients for signs of hypotension after initiating or titrating the dose of HYSINGLA ER. In patients with circulatory shock, HYSINGLA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of HYSINGLA ER in patients with circulatory shock. 5.9 Gastrointestinal Obstruction, Dysphagia, and Choking In the clinical studies with specific instructions to take HYSINGLA ER with adequate water to swallow the tablet, 11 out of 2476 subjects reported difficulty swallowing HYSINGLA ER. These reports included esophageal obstruction, dysphagia, and choking, one of which had required medical intervention to remove the tablet [see Adverse Reactions (6)]. Instruct patients not to pre-soak, lick, or otherwise wet HYSINGLA ER tablets prior to placing in the mouth, and to take one tablet at a time with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)].

(17)] Patients with underlying gastrointestinal disorders such as esophageal cancer or colon cancer with a small gastrointestinal lumen are at greater risk of developing these complications. Consider use of an alternative analgesic in patients who have difficulty swallowing and patients at risk for underlying gastrointestinal disorders resulting in a small gastrointestinal lumen. 5.10 Decreased Bowel Motility HYSINGLA ER is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. Opioids diminish propulsive peristaltic waves in the gastrointestinal tract and decrease bowel motility. Monitor for decreased bowel motility in post-operative patients receiving opioids.

The administration of HYSINGLA ER may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Hydrocodone may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis. 5.11 Cytochrome P450 3A4 Inhibitors and Inducers Since the CYP3A4 isoenzyme plays a major role in the metabolism of HYSINGLA ER, drugs that alter CYP3A4 activity may cause changes in clearance of hydrocodone which could lead to changes

in hydrocodone plasma concentrations. The clinical results with CYP3A4 inhibitors show an increase in hydrocodone plasma concentrations and possibly increased or prolonged opioid effects, which could be more pronounced with concomitant use of CYP3A4 inhibitors. The expected clinical result with CYP3A4 inducers is a decrease in hydrocodone plasma concentrations, lack of efficacy or, possibly, development of an abstinence syndrome in a patient who had developed physical dependence to hydrocodone. If co-administration is necessary, caution is advised when initiating HYSINGLA ER treatment in patients currently taking, or discontinuing, CYP3A4 inhibitors or inducers. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved [see Drug Interactions (7.1)]. 5.12 Driving and Operating Machinery HYSINGLA ER may impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Peak blood levels of hydrocodone may occur 14 – 16 hours (range 6 – 30 hours) after initial dosing of HYSINGLA ER tablet administration. Blood levels of hydrocodone, in some patients, may be high at the end of 24 hours after repeated-dose administration. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of HYSINGLA ER and know how they will react to the medication [see Clinical Pharmacology (12.3)]. 5.13 Interaction with Mixed Agonist/Antagonist Opioid Analgesics Avoid the use of mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) in patients who have received, or are receiving, a course of therapy with a full opioid agonist analgesic, including HYSINGLA ER. In these patients, mixed agonist/antagonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms. 5.14 QTc Interval Prolongation QTc prolongation has been observed with HYSINGLA ER following daily doses of 160 mg [see Clinical Pharmacology (12.2)]. This observation should be considered in making clinical decisions regarding patient monitoring when prescribing HYSINGLA ER in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that are known to prolong the QTc interval. HYSINGLA ER should be avoided in patients with congenital long QT syndrome. In patients who develop QTc prolongation, consider reducing the dose by 33 – 50%, or changing to an alternate analgesic.

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 (5.4)] • Hypotensive Effects [see Warnings and Precautions (5.8)] • Gastrointestinal Effects [see Warnings and Precautions (5.9, 5.10)] 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 1,827 patients were treated with HYSINGLA ER in controlled and open-label chronic pain clinical trials. Five hundred patients were treated for 6 months and 364 patients were treated for 12 months. The clinical trial population consisted of opioid-naïve and opioid-experienced patients with persistent moderate to severe chronic pain. The common adverse reactions (≥2%) reported by patients in clinical trials comparing HYSINGLA ER (20-120 mg/day) with placebo are shown in Table 2 below: Table 2: Adverse Reactions Reported in ≥2% of Patients during the Open-Label Titration Period and Double-Blind Treatment Period: Opioid-Naïve and Opioid-Experienced Patients Open-label Titration Period MedDRA Preferred Term

Double-blind Treatment Period

(N=905) (%)

Placebo (N=292) (%)

HYSINGLA ER (N=296) (%)

Nausea Constipation

16 9

5 2

8 3

Vomiting Dizziness

7 7

3 2

6 3

Headache Somnolence

7 5

2 1

2 1

Fatigue Pruritus

4 3

1 <1

1 0

Tinnitus Insomnia

2 2

1 2

2 3

Decreased appetite Influenza

1 1

1 1

2 3

The adverse reactions seen in controlled and open-label chronic pain studies are presented below in the following manner: most common (≥5%), common (≥1% to <5%), and less common (<1%).

The most common adverse reactions (≥5%) reported by patients treated with HYSINGLA ER in the chronic pain clinical trials were constipation, nausea, vomiting, fatigue, upper respiratory tract infection, dizziness, headache, somnolence.

The common (≥1% to <5%) adverse events reported by patients treated with HYSINGLA ER in the chronic pain clinical trials organized by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class were: Ear and labyrinth disorders tinnitus Gastrointestinal disorders abdominal pain, abdominal pain upper, diarrhea, dry mouth, dyspepsia, gastroesophageal reflux disease General disorders and administration chest pain, chills, edema site conditions peripheral, pain, pyrexia

Infections and infestations

Injury, poisoning and procedural complications Metabolism and nutrition disorders Musculoskeletal and connective tissue disorders

bronchitis, gastroenteritis, gastroenteritis viral, influenza, nasopharyngitis, sinusitis, urinary tract infection fall, muscle strain

decreased appetite arthralgia, back pain, muscle spasms, musculoskeletal pain, myalgia, pain in extremity Nervous system disorders lethargy, migraine, sedation Psychiatric disorders anxiety, depression, insomnia Respiratory, thoracic and mediastinal cough, nasal congestion, disorders oropharyngeal pain Skin and subcutaneous tissue disorders hyperhidrosis, pruritus, rash Vascular disorders hot flush, hypertension Other less common adverse reactions that were seen in <1% of the patients in the HYSINGLA ER chronic pain clinical trials include the following in alphabetical order: abdominal discomfort, abdominal distention, agitation, asthenia, choking, confusional state, depressed mood, drug hypersensitivity, drug withdrawal syndrome, dysphagia, dyspnea, esophageal obstruction, flushing, hypogonadism, hypotension, hypoxia, irritability, libido decreased, malaise, mental impairment, mood altered, muscle twitching, edema, orthostatic hypotension, palpitations, presyncope, retching, syncope, thinking abnormal, thirst, tremor, and urinary retention.

7 DRUG INTERACTIONS 7.1 Drugs Affecting Cytochrome P450 Isoenzymes Inhibitors of CYP3A4 Co-administration of HYSINGLA ER with ketoconazole, a strong CYP3A4 inhibitor, significantly increased the plasma concentrations of hydrocodone. Inhibition of CYP3A4 activity by inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may prolong opioid effects. Caution is advised when initiating therapy with, currently taking, or discontinuing CYP3A4 inhibitors. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved [see Clinical Pharmacology (12.3)]. Inducers of CYP3A4 CYP3A4 inducers may induce the metabolism of hydrocodone and, therefore, may cause increased clearance of the drug which could lead to a decrease in hydrocodone plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who had developed physical dependence to hydrocodone. If co-administration with HYSINGLA ER is necessary, monitor for signs of opioid withdrawal and consider dose adjustments until stable drug effects are achieved [see Clinical Pharmacology (12.3)]. 7.2 Central Nervous System Depressants The concomitant use of HYSINGLA ER with other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol can increase the risk of respiratory depression, profound sedation, coma and death. Monitor patients receiving CNS depressants and HYSINGLA ER for signs of respiratory depression, sedation and hypotension. When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced [see Warnings and Precautions (5.4)].

7.3 Interactions with Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) and partial agonist analgesics (buprenorphine) may reduce the analgesic effect of HYSINGLA ER or precipitate withdrawal symptoms in these patients. Avoid the use of mixed agonist/antagonist and partial agonist analgesics in patients receiving HYSINGLA ER. 7.4 MAO Inhibitors HYSINGLA ER is not recommended for use in patients who have received MAO inhibitors within 14 days, because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

No specific interaction between hydrocodone and MAO inhibitors has been observed, but caution in the use of any opioid in patients taking this class of drugs is appropriate. 7.5 Anticholinergics Anticholinergics or other drugs with anticholinergic activity when used concurrently with opioid analgesics may increase the risk of urinary retention or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention and constipation in addition to respiratory and central nervous system depression when HYSINGLA ER is used concurrently with anticholinergic drugs. 7.6 Strong Laxatives Concomitant use of HYSINGLA ER with strong laxatives (e.g., lactulose), that rapidly increase gastrointestinal motility, may decrease hydrocodone absorption and result in decreased hydrocodone plasma levels. If HYSINGLA ER is used in these patients, closely monitor for the development of adverse events as well as changing analgesic requirements.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C Risk Summary There are no adequate and well-controlled studies of HYSINGLA ER use during pregnancy. Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. In animal reproduction studies with hydrocodone in rats and rabbits no embryotoxicity or teratogenicity was observed. However, reduced pup survival rates, reduced fetal/pup body weights, and delayed ossification were observed at doses causing maternal toxicity. In all of the studies conducted, the exposures in animals were less than the human exposure (see Animal Data). HYSINGLA ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Clinical Considerations Fetal/neonatal adverse reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Observe newborns for symptoms of neonatal opioid withdrawal syndrome, such as poor feeding, diarrhea, irritability, tremor, rigidity, and seizures, and manage accordingly [see Warnings and Precautions (5.3)]. Data Animal Data No evidence of embryotoxicity or teratogenicity was observed after oral administration of hydrocodone throughout the period of organogenesis in rats and rabbits at doses up to 30 mg/kg/day (approximately 0.1 and 0.3-fold, respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons).

However, in these studies, reduced fetal body weights and delayed ossification were observed in rat at 30 mg/kg/day and reduced fetal body weights were observed in in rabbit at 30 mg/kg/day (approximately 0.1 and 0.3fold, respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons). In a pre- and post-natal development study pregnant rats were administered oral hydrocodone throughout the period of gestation and lactation. At a dose of 30 mg/kg/day decreased pup viability, pup survival indices, litter size and pup body weight were observed. This dose is approximately 0.1-fold the human hydrocodone dose of 120 mg/ day based on AUC exposure comparisons. 8.2 Labor and Delivery Opioids cross the placenta and may produce respiratory depression in neonates.

HYSINGLA ER is not recommended for use in women immediately prior to and during labor, when use of shorter acting analgesics or other analgesic techniques are more appropriate. HYSINGLA ER may 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. 8.3 Nursing Mothers Hydrocodone is present in human milk.

Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue HYSINGLA ER, taking into account the importance of the drug to the mother.

Infants exposed to HYSINGLA ER through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. 8.4 Pediatric Use The safety and effectiveness of HYSINGLA ER in pediatric patients have not been established. Accidental ingestion of a single dose of HYSINGLA ER in children can result in a fatal overdose of hydrocodone [see Warnings and Precautions (5.2)].

(5.2)] HYSINGLA ER gradually forms a viscous hydrogel (i.e., a gelatinous mass) when exposed to water or other fluids. Pediatric patients may be at increased risk of esophageal obstruction, dysphagia, and choking because of a smaller gastrointestinal lumen if they ingest HYSINGLA ER [see Warnings and Precautions (5.9)]. 8.5 Geriatric Use In a controlled pharmacokinetic study, elderly subjects (greater than 65 years) compared to young adults had similar plasma concentrations of hydrocodone [see Clinical Pharmacology (12.3)]. Of the 1827 subjects exposed to HYSINGLA ER in the pooled chronic pain studies, 241 (13%) were age 65 and older (including those age 75 and older), while 42 (2%) were age 75 and older.

In clinical trials with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were seen in the elderly patients who received HYSINGLA ER. Hydrocodone may cause confusion and oversedation in the elderly. In addition, because of the greater frequency of decreased hepatic, renal, or cardiac function, concomitant disease and concomitant use of CNS active medications, start elderly patients on low doses of HYSINGLA ER and monitor closely for adverse events such as respiratory depression, sedation, and confusion. 8.6 Hepatic Impairment No adjustment in starting dose with HYSINGLA ER is required in patients with mild or moderate hepatic impairment. Patients with severe hepatic impairment may have higher plasma concentrations than those with normal hepatic function. Initiate therapy with 1/2 the initial dose of HYSINGLA ER in patients with severe hepatic impairment and monitor closely for adverse events such as respiratory depression [see Clinical Pharmacology (12.3)].

8.7 Renal Impairment No dose adjustment is needed in patients with mild renal impairment. Patients with moderate or severe renal impairment or end stage renal disease have higher plasma concentrations than those with normal renal function. Initiate therapy with 1/2 the initial dose of HYSINGLA ER in these patients and monitor closely for adverse events such as respiratory depression [see Clinical Pharmacology (12.3)].

9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance HYSINGLA ER contains hydrocodone bitartrate, a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone. HYSINGLA ER can be abused and is subject to misuse, abuse, addiction and criminal diversion. The high drug content in the extended-release formulation adds to the risk of adverse outcomes from abuse and misuse. 9.2 Abuse All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited to the following examples: the use of a prescription or over-the-counter drug to get “high,” or the use of steroids for performance enhancement and muscle build up. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and include: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “Drug-seeking” behavior is very common to addicts and drug abusers. Drug seeking tactics include, but are not limited to, emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated claims of “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers, people with untreated addiction, and criminals seeking drugs to sell. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction. HYSINGLA ER can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures

that help to limit abuse of opioid drugs. Abuse may occur by taking intact tablets in quantities greater than prescribed or without legitimate purpose, by crushing and chewing or snorting the crushed formulation, or by injecting a solution made from the crushed formulation. The risk is increased with concurrent use of HYSINGLA ER with alcohol or other central nervous system depressants. Risks Specific to Abuse of HYSINGLA ER HYSINGLA ER is for oral use only. Abuse of HYSINGLA ER poses a risk of overdose and death.. Taking cut, broken, chewed, crushed, or dissolved HYSINGLA ER increases the risk of overdose and death. With parenteral abuse, the inactive ingredients in HYSINGLA ER can result in death, local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury. Parenteral drug abuse is commonly associated with transmission of infectious diseases, such as hepatitis and HIV. Abuse Deterrence Studies Summary The in vitro data demonstrate that HYSINGLA ER has physical and chemical properties that are expected to deter intranasal and intravenous abuse. The data from the clinical abuse potential studies, along with support from the in vitro data, also indicate that HYSINGLA ER has physicochemical properties that are expected to reduce intranasal abuse and oral abuse when chewed. However, abuse of HYSINGLA ER by the intravenous, intranasal, and oral routes is still possible. Additional data, including epidemiological data, when available, may provide further information on the impact of HYSINGLA ER on the abuse liability of the drug. Accordingly, this section may be updated in the future as appropriate. HYSINGLA ER contains hydrocodone, 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, oxycodone, and oxymorphone. HYSINGLA 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)]. 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. HYSINGLA ER should be discontinued by a gradual downward titration [see Dosage and Administration (2.6)]. If HYSINGLA ER is abruptly discontinued in a physically dependent patient, an abstinence syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms [see Warnings and Precautions (5.3) and Use in Specific Populations (8.3)].

10 OVERDOSAGE 10.1 Symptoms Acute overdosage with opioids is often characterized by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, sometimes, pulmonary edema, bradycardia, hypotension, and death.

Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations [see Clinical Pharmacology (12.2)]. 10.2 Treatment In the treatment of HYSINGLA ER overdosage, primary attention should be given to the re-establishment of a patent airway and institution of assisted or controlled ventilation. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques. The opioid antagonist naloxone hydrochloride is a specific antidote against respiratory depression that may result from opioid overdosage. Nalmefene is an alternative opioid antagonist, which may be administered as a specific antidote to respiratory depression resulting from opioid overdose. Since the duration of action of HYSINGLA ER may exceed that of the antagonist, keep the patient under continued surveillance and administer repeated doses of the antagonist according to the antagonist labeling, as needed, to maintain adequate respiration. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression.

Administer opioid antagonists cautiously to persons who are known, or suspected to be, physically dependent on HYSINGLA ER. In such cases, an abrupt or complete reversal of opioid effects may precipitate an acute abstinence syndrome. In an individual physically dependent on opioids, administration of the usual dose of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal syndrome 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, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.

CAUTION DEA FORM REQUIRED Healthcare professionals can telephone Purdue Pharma’s Medical Services Department (1-888-726-7535) for information on this product.

Purdue Pharma L.P. Stamford, CT 06901-3431 ©2015, Purdue Pharma L.P. U.S. Patent Numbers: 6,488,963; 6,733,783; 8,309,060; 8,361,499; 8,529,948; 8,551,520; 8,647,667 and 8,808,740.

This brief summary is based on Hysingla ER Prescribing Information 303511-0C, Revised 02/2015 (A)

100+ million people have chronic pain.

They want the most up-to-date and compassionate care available.

Show them you can provide it.

The American Academy of Pain Management offers Two TyPes of advanced education for clinicians who care for people with pain.

Choose the program that is right for you:

the general credentialed pain practitioner (gcpp)

the aDvanceD credentialed pain practitioner (acpp)

This general knowledge test, open to all clinicians who care for people with pain, is intended to evaluate the practitionerâ&#x20AC;&#x2122;s knowledge of pain management principles.

For MDs and DOs only, this program is designed to allow prescribers to demonstrate a superior level of knowledge, particularly about pharmacology.

NEW! streamlined credentialing application process!

Our new eligibility criteria make it easier than ever to apply to become credentialed: applicants must have two years of clinical experience and a valid clinical license without restrictions.

The application process is the same for both programs.

To apply, simply send us: 1. The application form 2. A copy of your clinical license 3. Your CV

DownloaD the application from the acaDemy website www.aapainmanage.org/credentialing anD begin toDay! email: credentialing@aapainmanage.org or call: (209) 288-2205

ACADEMY NE WS + RESOURCES

You Should Know...

The Academy Elects New Board Officers The Academy is pleased to announce the following: Joanna katzman, md, msph, has been named president of the Board of directors. dr. katzman, an associate professor in neurology, is the director of the university of new mexico pain Center and co-director of the unm project eCho Chronic pain program, which received the 2011 American pain society Clinical Centers of excellence Award. kevin Galloway, Bsn, mhA, is treasurer. A senior project manager at the defense and veterans Center for Integrative pain management (dvCIpm) in rockville, maryland, he recently retired from the united states Army after a distinguished 27-year career as an Army nurse Corps officer.

paul Christo, md, mBA, is secretary. dr. Christo is a board certified, harvard-trained anesthesiologist and hopkins-trained pain medicine specialist. he directed the multidisciplinary pain fellowship program at The Johns hopkins hospital for eight years, and directed the Blaustein Treatment Center at hopkins for five years.

The State Pain Policy Advocacy Network (SPPAN) The mission of SPPAN is to promote person-centered care for people affected by pain through advancing effective pain policy.

To achieve that goal, we strive to coordinate collective action whenever possible by focusing on three things: providing information, making connections, and taking action. With most legislative sessions convening in January, we want to share with you some ways that SPPAN has been, and will continue to be, working to improve pain policy for you and your patients and how you can get involved in advocating for improved pain policies during 2016.

we’ve Been workInG AlonGsIde numerous pArTners on our no. 1 polICy prIorITy: ACCess To, And reImBursemenT for, InTeGrATIve pAIn CAre.

14

Get Informed During 2015, SPPAN tracked roughly 1,300 bills and 700 regulations related to pain management, and we expect that 2016 will be just as busy. However, we do more than merely track—we analyze, summarize, discuss with experts, develop solutions, alert other advocates, and contact policymakers. When an issue is incredibly important and timely, we inform you, our Academy members, so that you can get involved. We hope that you do, as your expert opinions are vital for legislators and regulators to hear as they consider

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various pain-related policies.

If you would like to receive regular updates from SPPAN on important policy and advocacy opportunities, or if there is another way that we can help to inform your policy and advocacy efforts, be sure to contact us!

Get Connected As a network of leaders representing a variety of health care and consumer organizations and individuals, SPPAN was founded on the notion that we can achieve more working together than separately.

To that end, we have been working alongside numerous partners on our No. 1 policy priority: access to, and reimbursement for, integrative pain care.

In the coming year, SPPAN’s director will be joining the steering committee of the Coalition for Patients’ Rights and Provider Non-Discrimination in order to establish legislative and/or regulatory enforcement of the Affordable Care Act’s Section 2706, the vital provider non-discrimination provision, consistent with Congressional intent. The first target state for this important effort is Minnesota.

If you are a part of a local or national policy and advocacy effort that may be able to work alongside SPPAN, please let us know so that we may

continue to expand our network of committed and passionate advocates.

Take Action!

While we do our utmost to simplify taking action by reaching out to advocates with summaries, analyses, and pre-written letters that are easily submitted to policymakers, we are often asked how a busy health care practitioner or person living with pain can become more involved in shaping policy. Last September, we were able to help one such aspiring advocate by sending her to participate in an advocate training event put together by the National Patient Advocate Foundation (at which SPPAN staff members Amy Goldstein and Katie Duensing were trainers).

This year, with that training to fuel her, that same advocate will be taking part in the above-mentioned Coalition for Patient Rights and Provider Non-Discrimination.

If you or one of your pATIenTs would lIke To leArn how To GeT Involved In polICy And AdvoCACy efforTs, vIsIT us onlIne AT sppAn.AApAInmAnAGe.orG, or ConTACT Amy GoldsTeIn, sppAn dIreCTor, AT AGoldsTeIn@AApAInmAnAGe.orG.

ACADEMY NE WS + RESOURCES

AcAdemy lAunches All-new, Online PAin cAre leArning center

Academy Contributors Donations to the American Academy of Pain Management (the Academy) support the vital work of the Academy’s policy and advocacy efforts—efforts aimed at ensuring that people with pain have access to the care they need and deserve.

The Academy’s commitment to this work is evidenced by the fact that it is the only pain management organization in the US with a dedicated in-house policy/advocacy team, which is guided by Bob Twillman, PhD—one of the nation’s most respected pain policy leaders. Dr. Twillman carries the Academy’s positions on key issues to policy makers on both the state and federal levels. The Academy’s growing state advocacy efforts are led by Amy Goldstein, MSW, State Pain Policy Advocacy Network (SPPAN) director.

The Academy recently launched an online learning management center dedicated to providing education on caring for people with chronic pain. This new section of our website contains audiovisual presentations and written educational activities that are accredited for continuing education. This on-demand system provides members access to accredited education and allows users to print certificates and access their continuing education history at any time.

Go To eDUcATIoN.AAPAINMANAGe.orG To AcceSS The ProGrAMS ToDAy.

Credentialing Application Process Now Streamlined

We would like to thank the following contributors for their donations in support of the Academy’s policy and advocacy effort.

Andrew MAciAk, dc, ccrd, dAAPM, dABFe Anne V. XAVier, Md AVAni P. Sheth, Md cAndido r. MArtinez-MAnguAl, Md cAthryn y. hu, Phd, oMd, lAc dAniel Shu-eng chen, Md denniS Quincy McMAnuS, Md doMinic u. chiBueze, Md dr. John J. delFino, dMd eric k. willMArth, Phd gregory Pierce, Md JAMeS F. hooPer, Md kenneth A. leVin, Md MArk Brown, Md MichAel A. PAlMer, Md

In Memory PAul A. deVore, Md, cMd dAVid A. Stone, do leoPold liSS, Md AlBert ridloVSki, Md kiAnnA StewArt, PA-c williAM J. StAlcuP, do

nick J. reinA, Md roBert e. McMAhon, ddS SAMir k. BAllAS, Md SheilA J. BrookS, dPM StePhen l. giPSon, Md Sudhir r. dAFtAry, Md terecitA l. deAn, ddS urFAn A. dAr, Md young-Sun yi, Md zAki AnwAr, 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.

In memory of our deceased members gABriel r. PereirA, Md AlAn r. glock, Md Scott M. kuhnert, Md MichAel t. howArd, Md leroy J. Pelicci, Md

100+ million people suffer with chronic pain. Show them you can provide the care they need. it’s now easier than ever to apply to become credentialed.

how to Apply 1. complete the credentialing Application 2. Submit a copy of your clinical license 3. Submit your c.V. note: Applicants must have two years of clinical experience and a valid clinical license without actions or restrictions.

credentialing Programs —The General Credentialed Pain Practitioner this general knowledge test is open to all clinicians who care for people with pain. earn one of the following designations: diplomate (dAAPM), Fellow (FAAPM). or clinical Associate (cAAAPM).

—The Advanced Credentialed Pain Practitioner Program For Mds and dos only, this program is designed to allow prescribers to demonstrate a superior level of knowledge, particularly about pharmacology. earn the designation Advanced diplomate (AdAAPM).

QUeSTIoNS? VISIT AAPAINMANAGe.orG/creDeNTIAlING, cAll 209-288-2205, or eMAIl creDeNTIAlING@AAPAINMANAGe.orG.

new: Free membershiP FOr students & residents!

Be a part of the largest professional pain management organization in the country! The American Academy of Pain Management is pleased to offer complimentary memberships to full-time students and residents. Benefits include: • Access the Academy’s “Members Only” section of the website • Access to the online learning center • A printable membership certificate To qualify for a free membership, you must provide proof of full-time student or resident status annually.

This WEEK in pain To find out what happened in pain news this week, check out our new web column.

www.aapainmanage.org/category/ this-week-in-pain/

JoIN ToDAy AT WWW.AAPAINMANAGe.orG/MeMBerShIP/

T H E PA I N P R AC T I T I O N E R

| VOLUME 25, NUMBER 4 |

15

More Answers, ButYet So Many Questions

By Chris Tine rhoDes, Ms

T

he theme of the 26th Annual Clinical Meeting of the American Academy of Pain Management No Life Limited by Pain embodies the new vision of the Academy—to care for people with pain in such a way that their lives are not limited by the pain they might be experiencing. Doing so requires not only understanding the latest research developments but also appreciating the varied contributions made by individual members of the pain care team to best serve our patients’ multiple needs.

The Academy is unique in providing continuing education for 10 different specialties and including a diverse group of practitioners among its attendees.

At this year’s meeting, Executive Director Robert Twillman, PhD, marked the completion of his first year of service, and Academy President Robert Bonakdar, MD, turned the presidential reins over to Joanna Katzman, MD, MSPH, who will serve for a period of two years. A two-day review course for clinicians preparing for the Academy’s Advanced Credential in Pain Management was offered.

Shared Interest Groups (SIGs) were formed around nutrition, federal medicine, and interprofessional care, and met to discuss their particular agendas. As in previous years, preconference sessions focused on opioid prescribing, chaired by W. Clay Jackson, MD, DipTh, and myofascial pain, chaired by Jay P. Shah, MD. A new session on integrative approaches to pain management was chaired by Jay Sandweiss, DO. A total of 74 exhibitors were on hand to demonstrate their company’s new products and services and gain valuable feedback from attendees during breaks from the educational sessions. Herewith is an overview of this year’s annual meeting with a closer look at a few of the key topics presented.

Pain in the Military

The location of this year’s meeting near Washington, DC, provided a unique opportunity to include a keynote presentation by Wayne B. Jonas, MD, president and CEO of 16

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the Virginia-based Samueli Institute, a nonprofit research organization dedicated to exploring the science of healing, as well as several presentations by faculty affiliated with the Department of Defense (DOD) and the Veterans Administration (VA). Dr. Jonas spoke about strategies to use in clinical practice for addressing the Institute of Medicine’s call for a cultural transformation in pain management.

Lucile Burgo-Black, MD, Stephen C. Hunt, MD, MPH, and Michael Saenger, MD, presented the VA’s vision to include integrative approaches to pain. Kathryn Calabria, DO, DABMA, C-NMM, FA, presented a workshop on battlefield acupuncture. Keynote speaker Eric B. Schoomaker, MD, PhD, and retired Lieutenant General of the US Army, talked about pain in the military and how it has come to be managed in a comprehensive way using complementary and integrative practices. Improvements in battlefield care due to better training of medics along with improved evacuation techniques have resulted in survival in combat today that is better than in any war we have fought. He cited the Air Force for “an incredible job of what we call strategic evacuation, being able to convert, for all intents and purposes, an 8,000-mile front or evacuation chain into a single trauma support system.” In addition, according to Dr. Schoomaker, “The Joint Trauma System of research nurses and physicians is able to collect information retrospectively and to provide us evidence for changing our protocols.”

These have resulted in improvements in treating musculoskeletal disorders, which include the wear and tear of carrying heavy loads in combat and the chronic pain that ensues. Traumatic brain injury from concussion injuries incurred during bombardment is also now being understood and managed. Unfortunately, the consequences of these conditions are still unchanged, which include unintentional drug overdose, not from illegal drugs but from prescription opioids, either diverted or inappropriately used.

“The soldier I remember most,” Dr. Schoomaker said,

A 20009 VA V st tudy showed thAt About ry hAlf t th he m miilitAr pop opu ulAtiion w wAs suffe ffer ring fr fro om neous p pAin in,, sim imu ultAn posttr trA Aum mAtic c stre st res ss, And conc oncu ussiVe iin nju jur ry.

“had traumatic brain injury coupled with PTSD who was treated with psychotropics and opioids, who then goes to his barracks and adds the third major drug, alcohol, and he’s found dead. And that was a wakeup call for many of us.” A 2009 VA study showed that about half the military population was suffering from simultaneous pain, posttraumatic stress, and concussive injury. These conditions, together with the depression, anxiety, somatic disorders, and substance use and abuse that result during combat have been called the “trauma spectrum response.” Treatment “fits very closely with what we in the military call the Total Force Fitness model,” said Dr. Schoomaker, “which is a biopsychosocial model for well-being and wellness in which not just health care alone—health care only impacts this to about 20%—but all aspects of life, community involvement, spiritual involvement, family involvement, nutrition, self-care, all contribute to the well-being of the individual and their success and their function.”

Dr. Schoomaker talked about the unprecedented collaboration between the VA’s pain program, the Pain Management Task Force within the DOD, the Institute of Medicine’s report on pain in America, and the National Center for Complementary and Integrative Health.

Collaboration between these groups is culminating this year with the release of a National Pain Strategy. “In my world,” Dr. Schoomaker said, “if we can save an individual even 5% of his or her dose of opioids, if we can reduce a nighttime dose by giving someone acupuncture before they go to sleep so that they don’t have to be self-administering a narcotic load at night, we’ve saved something that is going to make a difference in that young man or young woman’s life.”

Opioids

It is clear that despite the growing acceptance of integrative practices for pain management, the use of opioids continues to be a mainstay of treatment. Sessions at the annual meeting reflected the current concerns that are top of mind for clinicians, ranging from how to use the drugs effectively to how to properly follow the guidelines set by regulatory agencies. Andrea D. Furlan, MD, PhD, explained how to use adjunctive medications for chronic pain and some of the differences between analgesics, many of which result in drug interactions. Jeffrey A. Gudin, MD, presented the latest evidence on the physiology of pain and mechanisms of opioid-induced hyperalgesia. Clinicians should suspect opioid-induced hyperalgesia when the treatment effect 18

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seems to wane in the absence of disease progression, or if there is new unexplained pain or increasing pain with increasing dosages of the opioid. There are still many unanswered questions that are just beginning to be explored.

The ethics of opioid contracts and agreements were presented in a theoretical discussion by Richard Payne, MD, who proposed that informed consent was a more ethically justifiable option for pain management. Informed consent represents a paradigm shift in chronic pain policy representing a more patient-centered and shared decisionmaking model rather than the paternalistic one offered by opioid contracts. These contracts, Dr. Payne said, can leave us with the unintended consequences of shame and guilt and intensified mutual suspicion between patients and physicians. The net result is undertreatment of pain and an undermining of physician-patient trust.

Specific methods for drug monitoring were examined from several angles. Urine drug testing was discussed by Gary M. Reisfield, MD, who revealed that only about half of urine specimens come back with expected results. While some clinicians discount the value of point-of-care (POC) testing, which is generally performed in the office and is not as accurate as laboratory-based testing, Dr. Reisfield believes it has its rightful place in patient care because results are available within minutes and allow the clinician to address any issues immediately with the patient.

Dr. Reisfield described some of the common reasons for discrepancies in POC testing and when to follow up with more intensive laboratory testing. Brett Badgley Snodgrass, MSN, APRN, FNP-C, explained the inception and past use of the Controlled Substance (Prescription Drug) Monitoring Database, how some states are using it, and what the future may hold for its use. Ultimately, however, said Ms. Snodgrass, it is physician education on the safe and effective use of opioids that may do more to reduce opioid prescribing than access to Prescription Drug Monitoring Programs. Sean P. Kelly, MD, presented the DEA requirements for electronic prescribing of controlled substances (EPCS), as well as some of its advantages and disadvantages. Dr. Kelly spoke of EPCS is an important way to get at the problem of drug abuse and diversion by addressing issues further upstream in the delivery process.

Headache

Innovations in treatment of several common pain conditions is, of course, always a key feature of the Academy’s Annual Clinical Meeting, and this year’s presentations did

Gary M. reisf sfiiel eld d, Md, r re eve veal ale ed t tha hat only ab bou out t ha half of of urin ine es sp peciMens coM Me back b wiith expecte ected d resul esults s.

not disappoint. Duren Michael Ready, MD, gave two, twohour workshops on advanced headache management, first differentiating primary and secondary headaches and their treatment, and then discussing what to do when nothing is working. Dr. Ready talked about the impact of stress and psychological problems on patients’ pain. He emphasized that patients need to take an active role in their treatment and have realistic expectations for reducing headache frequency and intensity, but not necessarily eliminating them.

In addition to providing drug regimens for different types of headache, he asked attendees to think outside the box and prescribe unconventional methods for empowering their patients to deal with their headache pain.

It turns out that there are several risk factors for migraine, and one of the modifiable ones is obesity. Keynote speaker B. Lee Peterlin, DO, discussed some of the possible mechanisms for these two disorders to be associated, particularly through central and peripheral mechanisms and pain pathways. She presented data suggesting that specific obesity-related proteins called adipocytokines may be novel migraine biomarkers or drug targets. Epidemiological studies have confirmed that obesity is comorbid with migraine, with obese women in their reproductive years at greatest risk for migraine. This risk increases with increasing obesity status, and the transformation from episodic headache to chronic migraine also increases in obese individuals.

Studies have shown that the hypothalamus is associated with both migraine and obesity. Many drugs used in migraine therapy also target the neurotransmitters and proteins that have a role in satiety. Others increase the drive to feed. The hypothalamus regulates obesity via adipose tissue, which is, in fact, a highly functioning endocrine organ. Research has shown that during fasting, levels of the adipocytokine adiponectin increase, while levels of leptin, another adipocytokine, decrease. Such increases in adiponectin lead to stimulation of some of the same pathways that have been implicated in migraine. Other neurotransmitters have receptors in the hypothalamus and can activate other pathways, including those involved in inflammation. These findings led Dr. Peterlin and her team to ask, “Could obesity-related proteins be part of migraine, either in regard to increasing the inflammation or being involved on the pathway to migraine?”

Further research confirmed that adiponectin and resistin levels were significantly increased in people with migraine as compared to controls. Moreover, adiponectin levels could be a biomarker for migraine, specifically, as a 20

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marker for an individual’s response to treatment. This was confirmed in studies that correlated decreases in adiponectin and resistin levels with treatment response, while leptin levels remained unchanged. Stay tuned for more developments in this evolving area of molecular medicine.

Technological Advances in Pain Treatment

In another keynote presentation of cutting-edge research, Anita Gupta, DO, PharmD, discussed whether pharmacogenetic testing can improve the treatment of pain. She pointed out that the practice of medicine is getting better and better because of technological advances. For example, genetic testing has become much lower in cost, imaging techniques have become more accurate, and patients are more informed and involved in their care because of technology. Health care costs are shifting from end-of-life care to preventive care. Data from thousands of EMRs are being mined to understand patterns of health and disease.

Studying genetic data, especially those associated with pain management, offers us the possibility to predict how our patients would do under select conditions.

The cost of gene sequencing has fallen so low as to become affordable, allowing precision medicine to become a reality. Integrating precision medicine into health care is, in fact, one of President Obama’s priorities. However, we still don’t know completely what impact this information will have on patients. Pharmacogenomics can predict negative health outcomes for people who may develop certain conditions in certain communities. It can be used to personalize a patient’s drug regimen based on his or her type of metabolism. We can use pharmacogenomics to determine whether or not we can prevent a negative outcome. “Doing this is proactive for our patients and it helps us participate in what patients are interested in: predicting good health, keeping them healthy, preventing complications, keeping them out of the hospital, keeping them out of the ICU, and minimizing costs, because that’s where we are in health care, doing things better, doing it smaller, doing it cheaper, exponentially,” said Dr. Gupta. There is even emerging science in genetics that may in the next several years tell us that there is a genetic component to how people sense pain.

Pharmacogenetics refers to how genetic variability impacts a person’s response to medication. Genetic variations, or polymorphisms, can impact the way medications act and how people respond to them. For example, polymorphisms can result in unexpected metabolic changes by cytochrome P450, leading to unexpected medication out-

Studyiing Stu genetic d data offe ffer rS u uS St th he poSSibility to to pre red dict ho how our patientS woul ld do ele ect under Sel con ond dition onS S.

comes, and pharmacogenetic testing can help predict which patients will be poor, intermediate, or ultra-rapid metabolizers. This can help clinicians understand why their patients are asking for dose increases or to switch to another pain medication, or why certain drug combinations may be toxic. “It takes time for physicians to learn how to implement these results,” said Dr. Gupta. “But if you’re like me, I prescribe probably 25 drugs very frequently that I know I’m very comfortable with, that I know that work very well on my patients, and I know how they’re metabolized.”

The use of hormone testing and treatment in pain care is also evolving. Only a few hormones are involved in pain care and administration of hormones is remarkably safe, compared to some of the drugs commonly used in pain care, according to speaker Forest Tennant, MD, DrPh. Testing can help determine a patient’s individual hormone profile and needs for replacement resulting in significant improvements in pain management.

Acupuncture

Despite these new developments through the use of technology, there is still much to learn about how and why traditional therapies work. For example, the role of acupuncture in integrative pain management was discussed

by Ian Koebner, MSc, MAOM, LAc. “We don’t know the origins of acupuncture, but it has become commonplace, with 3.2 million Americans using it within the past 12 months,” he said. Most received from one to 10 treatments that, because of insurance restrictions, were paid for out of pocket. Acupuncture’s mechanism of action may be largely unknown, but studies have concluded that it is “effective for the treatment of chronic pain and therefore a reasonable referral option. Significant differences between true and sham acupuncture indicate that acupuncture is more than a placebo. However, these differences are relatively modest, suggesting that factors in addition to the specific effects of needling are important contributors to the therapeutic effects of acupuncture.”

Factors Influencing Pain

Clearly, pain management is not a simple matter and many factors can influence outcomes. Pain and racial and ethnic disparities were discussed by Lara Dhingra, PhD, Tamara A. Baker, PhD, and Burel R. Goodin, PhD. Such disparities, though not well studied, influence patients’ pain appraisal, the interpretation of their pain, the meaning of their pain, and their desire for treatment. And these factors 22

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in turn can influence how health care providers assess and manage patients’ pain. Studies on how pain outcomes and treatment affect different race and ethnic minority groups are needed so that we can identify potential gaps in the quality of pain care and improve access to care.

The vast majority of patients present to primary care when they have chronic pain. However, we have a great need to develop better models to integrate pain management into the comprehensive medical and psychosocial care of primary care patients. Dr. Dhingra described a study of economically disadvantaged patients with chronic, severe pain that showed that Hispanic patients are at higher risk for potential undertreatment in emergency room, primary care, and postoperative settings.

Dr. Baker continued with an examination of some of social determinants that contribute to racial and ethnic disparities in health care and pain care, particularly in marginalized populations. The Centers for Disease Control and Prevention and the World Health Organization have described five domains that are addressed within social determinants of health: neighborhood and built environment, education, economic stability, health and health care, and social and community context. Under each domain are different factors contributing to these health disparities. Looking at disparities from the point of view of social determinants allows us to examine both socioecological and medical factors together. Dr. Baker summed up her presentation with a quote: “Good health is more than just having access to care. It is important to consider what happens before an individual needs to go to a doctor and to consider what is happening in the community where that individual lives. Where people live, work, worship, and play, which are all social determinants of health, has a greater impact on health outcomes than having access to a physician.”

Dr. Goodin finished with a discussion of his research on sleep and chronic low back pain and differences between black and white individuals. Most patients consider pain to be the forecaster of poor sleep, but Dr. Goodin has found that, surprisingly, sleep disturbance is a stronger predictor of future pain than pain is of future sleep disturbance. In addition, there is poor correspondence between diagnostic imaging and the extent and severity of a person’s chronic low back pain, which really suggests there are other biopsychosocial mechanisms that may predict the severity of pain and the disability that goes along with it. Can we make that statement for most areas of chronic pain management?

Absolutely.

Raciial an and d ethni hnic c di dis spaR Rities inf in fluence p patie ien nts tsâ&#x20AC;&#x2122;â&#x20AC;&#x2122; pain n ap app pRais aisal,, the th e iinte nteR RpRetatio on of th theiR p paiin, the meaning of paiin, an and theiR p theiR d de esiRe f fo oR tReatme ent nt.

Blue Ribbon Poster Abstracts Which chronic Back Pain Patients have arachnoiditis?

Methods: A 21-item questionnaire was given to 26 patients

Presenter: Forest Tennant MD, DrPH Author: Forest Tennant MD, DrPH Background: Low back pain is the most common problem

with arachnoiditis, which was documented by magnetic resonance imaging (MRI). Specific questions were selected from a review of the literature and clinical observations of patients. Questions were directed at the presence of positional pain, bowel and bladder function, physical dysfunctions, character of the pain, and symptoms indicative of cerebrospinal fluid obstruction.

that brings a patient to pain treatment. While the cause of low back pain in the majority of cases is degenerative in nature, an unknown, but definite percentage, have arachnoiditis. This condition, which appears to be increasing in incidence, can be catastrophic in that it is an inflammatory, progressive process that may cause severe, disabling pain, lower extremity paralysis, bowel and bladder dysfunction, sexual inability, and a systemic autoimmune disorder.

Although previously thought to be a hopeless disease, recent reports show significant improvement and recovery in patients who receive specialized pain and neurogenic management.

Results: Remarkably all 26 patients reported that their pain was constant and that: (1) severe pain occurred with standing too long, which caused the patient to sit or lie down; and (2) jerking or tremors in their legs. At least 23 of 26 (88.5%) patients reported: (1) intense episodes of heat and sweating; (2) difficulty with initiation of urination and/or defecation, and; (3) episodes of blurred vision.

All patients had undergone a wide variety of spinal surgeries and procedures.

Objective: To provide a short, simple, clinical interview

Conclusions: Since arachnoiditis is increasing in inci-

that pain practitioners can use to identify the lower back pain patient who requires a diagnostic evaluation for the presence of arachnoiditis.

dence and perhaps the most catastrophic, disabling pain condition, it is essential that every back pain patient be quizzed for symptoms of arachnoiditis. A patient should be suspected to have arachnoiditis if he or she has a typical clinical profile which consists of inability to stand long without severe pain, tremors, or jerking in the legs, intense episodes of heat and sweating, difficulty initiating urination or defecation, and episodic blurred vision.

References:

Forest Tennant MD, DrPH, left, and Academy Board member Thomas N. Watson, DPT, MEd, DAAPM

1. Aldrete JA. Suspecting and diagnosing arachnoiditis. Pract Pain Manage. 2006;6(1):72-82.

2. Tennant F. Adhesive arachnoiditis. Pract Pain Manage. 2014;14(7):63-69.

Disclosure: This study was supported by the

Tennant Foundation.

Diverse OpiOiD pathways in ChrOniC pain reCOvery Presenter: Bruce Singer, PsyD Authors: Seddon Savage, MD; Brent Moore PhD; Bruce

Singer PsyD; Seth Resnick, MD; Michael Brennan, MD; Michael Fortin, DPT; Tiffany Nienstedt, MS; and Sigurd Ackerman, MD Background: While some patients with chronic pain experience effective analgesia with opioid therapy, over time other patients experience loss of analgesia, declining function, persistent side effects, mood changes, increasing pain, escalating dose requirements, and/or diverse types of opioid misuse that ultimately result in declining well-being. A patient’s distress in such contexts may reflect diverse issues including: • Ineffective pain management due to tolerance, hyperalgesia, opioid non-responsiveness, or inappropriate dosing • The presence of unaddressed, co-occurring symptoms that facilitate pain such as depression, anxiety, intrusive memories, sleep disturbance, or others • Opioid-induced distress related to active opioid misuse or addiction • A combination of these Objective: To address chronic pain in patients who have

not responded favorably to opioid therapy, the Chronic Pain & Recovery Center (CPRC) at Silver Hill Hospital TABle 1 The numbers of common pain diagnoses and psychiatric and substance abuse disorders in the first 154 patients admitted to the program.

Pain Diagnoses 95 MusculoskeletalAxial 34 Musculoskeletaljoint/limb 18 Neuropathic (non-facial) 15 Headache 9

Abdominal

5

Facial

2

Genital

15 Other

Psychiatric and Substance Abuse Diagnoses* 114 Depressive disorder or state* 79 Anxiety disorder or state 10 PTSD 4

Bipolar disorder

72 Opioid use disorder 45 Sedative hypnotic use disorder 35 Alcohol use disorder

*Patients could be diagnosed with more than one pain or psychiatric disorder.

Payer sources were 54% self-pay, 30% workers compensation, 2% Veterans Administration, and 14% scholarship.

Bruce Singer PsyD, presents his poster in the exhibit Hall.

(SHH) is guided by the following understandings: • Chronic pain, like other chronic medical conditions, often has complex biopsychosocial contributors and benefits from a strong foundation in self-management.

• Distress occurring in the treatment of chronic pain with opioids can reflect diverse drivers, therefore opioid management must be tailored to the individual and the causes of distress; no single approach is effective in addressing the needs of all patients.

• Outcomes of treatment based on these guidelines are presented.

Methods:

Admission criteria and process All patients have one or more pain diagnoses. Many have co-occurring psychiatric or addictive disorders. Treatment costs are covered by the individual, workers compensation, the Veterans Administration, or through SHH scholarships covering 75% of cost.

Patients are admitted to the program by two routes: • On a non-urgent, elective basis following outpatient evaluation by the CPRC team.

• On transfer from inpatient psychiatric admission for acute mental health or addiction issues with chronic pain; evaluated by the CPRC team once stable.

Patient characteristics Table 1 indicates the numbers of common pain diagnoses and psychiatric and substance abuse disorders in the first 154 patients admitted to the program.

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ClINICAl OUTCOMeS Patients Completing Residential Treatment

Brief Pain Inventory

Admit

Discharge

p

Average Pain

6.6

4.8

<.001

Interference with enjoyment

7.9

3.7

<.001

Interference with activities

7.0

3.5

<.001

Admit

Discharge

p

Beck Anxiety Inventory

26.0

14.2

<.001

Beck Depression Inventory

30.1

10.9

<.001

Pain Catastrophizing Scale

Admit

Discharge

p

Total

30.7

14.6

<.001

Rumination

10.9

5.7

<.001

Magnification

5.7

2.8

<.001

Helplessness

14.1

6.2

<.001

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Patients Completing Plus Six Months of Aftercare

Brief Pain Inventory Average Pain, M (SD) Interference with enjoyment, M (SD) Interference with activities, M (SD)

Admit 6.8a (1.9) 7.6a (2.7 6.8a (3.0)

Discharge 5.0b (2.6) 3.7b (3.2) 3.8b (3.2)

3 mos 4.6b (2.4) 3.7b (3.3) 4.3b (3.4)

6 mos 4.8b (2.4) 3.5b (3.6) 4.4b (3.4)

Admit Beck Anxiety Inventory Score (n =25) Total Score, M (SD) 25.3a (13.8) Beck Depression Inventory Total Score, M (SD) 29.7a (13.9)

discharge (n =24) 13.1b (10.2)

3 mos (n =23) 15.3b (11.9)

6 mos (n=18) 15.3b (13.4)

11.2b (10.5)

14.3b,c (12.4)

16.9c (14.9)

pain catastrophizing scale Admit Total, M (SD) 32.9a (14.2) Rumination, M (SD) 11.8a (4.4) Magnification, M (SD) 6.6a (3.5)

discharge 16.2b (13.0) 6.4b (5.5) 2.9b (2.6)

3 mos 15T.8b (14.8) 5.6b (5.1) 2.6b (2.8)

6 mos 17.3b (14.7) 6.6b (5.3) 3.6b (3.4)

p <.001 <.001 <.001

p <.001

<.001

p <.001 <.001 <.001

Treatment Program format and goals: The CPRC is a minimum four-week, residential program with a maximum census of eight patients. The program focuses on acquisition of self-management skills with goals to reduce pain, improve coping with residual pain, increase function, effectively treat co-occurring disorders (mental health or addiction), reduce medication reliance, and enhance overall quality of life. Patients engage in therapeutic activities 12 to 14 hours a day. Treatment is primarily groupbased with individual counseling sessions with a psychologist a minimum of twice weekly and medical/psychiatric appointments from one to five times a week as indicated.

Core treatment approaches include: • Cognitive behavioral therapy (CBT) integrated with acceptance and commitment therapy (ACT) tailored to comprehensively address pain, mood, and substance disorders • Mindfulness strategies including meditation, body awareness, gratefulness • Physical therapy tailored to individual condition – Land-based exercise (aerobic, stretch, strengthening) – Aquatic exercise • Goal setting and process groups • Education on pain, mood, substance use, sleep hygiene, nutrition, and related topics Patients also participate in: • 12-step groups including Chronic Pain Anonymous, AA, NA • Movement groups including yoga, Tai Chi, Chi Gong • Art therapy • Family program • 12-month step down aftercare and telephone support follow-up is offered

Medication management All patients using opioids without favorable response or with negative consequences are educated about ways in which opioids can contribute to distress and are encouraged to taper off on a trial basis. Decisions regarding ongoing management of opioids are made with the patient based on his or her response to taper.

Common management approaches include: • Opioid taper with continued cessation (with or without naltrexone) • Transition to opioid agonist maintenance therapy for opioid addiction (buprenorphine/naloxone or methadone maintenance) • Rotation to an alternative opioid at lower doses for analgesia • Lower dose therapy using the admission opioid for analgesia Psychiatric medications are adjusted as indicated to treat co-occurring psychiatric issues. Non-opioid medications for pain are introduced or adjusted as indicated.

Results: One hundred eighteen of the first 136 patients admitted completed treatment and had assessment data analyzed. Clinical outcomes for pain, pain interference, mood, and catastrophizing are indicated in the graphs on page 26. Data indicates significant reductions in mean pain and pain interference with enjoyment of life and with activity. Anxiety and depression scores significantly reduced, as did scores from the pain catastrophizing measures. Data available at three and six months after initiation of treatment on a smaller group of 18 patients who participated in aftercare suggest that these improvements persisted.

Opioid use data is available on 154 patients who completed treatment and indicates the following:

OPIOID OUTCOMeS

Table 2. Opioid Status Six Months Post Treatment (N+19) Discharge Statues # Status at 6 mos No Opioids 13 12/13 Off Opioids, 1 for Pain OAT for Addiction 3 3/3 Bup/nx Analgesis Opioids 3 3/3

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• 79% of 154 (122) patients admitted to CPRC were using opioids on admission.

• 63% of those admitted on opioids (77) no longer used opioids at discharge – 3 of these were on the depot naltrexone to support recovery from opioid addiction.

• 18% (22) were transitioned to opioid agonist therapy (OAT) for treatment of opioid addiction.

– 20 on buprenorphine/naloxone – 2 on methadone with referral to methadone maintenance • 19% (23) were on lower dose opioid prescriptions for pain, most rotated to a different opioid with a mean dose reduction of greater than 75% morphine equivalents.

• One patient with history overuse of prescribed opioids and relapsing alcoholism (in part driven by pain) who was not on opioids at admission, was prescribed buprenorphine/nx for pain.

• One patient’s admission opioids were unchanged on discharge.

Opioid use data at six months post discharge based on self report and urine drug screens on 19 patients in aftercare (see Table 2) indicate maintenance of discharge opioid status for all but one patient.

Conclusions: From treatment intake to discharge, all mea-

sures of pain, pain interference, and measures of psychiatric functioning (anxiety and depression) showed significant clinical improvement. For participants in the aftercare program, improvements appear to be retained for the pain measures.

There is some indication that anxiety and depression scores at later follow-up may be returning toward baseline.

Importantly, these clinical improvements occurred in the context of reduction or elimination of opioid use for pain.

Opioid management generally followed these principles: • Patients were transitioned to OAT for addiction or taken off opioids and prescribed depot naltrexone if they were determined to have moderate to severe opioid use disorder (OUD).

– OAT was prescribed to patients with histories of relapsing opioid addiction, high levels of craving, or other variables indicating strong potential for relapse or opioidassociated harm.

– Naltrexone was considered in patients with recent onset addiction, no history of prior addiction or addiction treatment, and/or those who declined OAT. • Patients were tapered and discharged off opioids without naltrexone if: – Opioids were ineffective for pain but they had no co-

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occurring opioid use disorder – They had misused opioids targeting relief of pain or other symptoms/distress but were not judged to have triggered addiction (absent craving, history of relapses, past opioid addiction, or other indicators) or – They were identified as having moderate to severe OUD but declined OAT or naltrexone.

• Opioids were continued or resumed for analgesia if no major OUD was identified and impairing pain persisted during or after opioid taper and interfered with function and/or program engagement despite introduction of self-management strategies and use of non-opioid analgesic approaches.

• In this treatment population for whom opioid analgesic therapy was previously unsuccessful or associated with misuse or harm, upward titration of opioids for pain was not identified as useful.

Limitations and further study The study is limited to patients in residential treatment for chronic pain, and may not generalize to other populations.

In addition, although standardized assessment measures were used, all assessments were based on self-report. Finally, both clinical and opioid use follow-up data is limited to patients who actively participated in an aftercare program,

Has EHR Been a Pain?

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so the persistence of clinical improvement in patients with less support following discharge is unknown.

Future evaluations will include: • Analysis of the relationship of opioid management strategies implemented and their association with different pain types, mental health diagnoses, and other patient variables.

• How opioid use changes over time post-treatment to determine the long-term effectiveness of different opioid management options for different patients.

• Examination of which ongoing self-management practices (exercise, cognitive awareness, meditation, etc.) at what intensity of practice are associated with best clinical outcomes.

These outcomes suggest that intensive residential engagement in self-management can improve chronic pain, function, and quality of life at the same time reliance on opioids is reduced. Opioid management strategies associated with positive pain treatment outcomes vary according to patient clinical variables and may include: • Opioid cessation (with or without naltrexone) • Transition to opioid agonist treatment for opioid addiction • Opioid rotation and reduction in equivalent opioid dose • Reduction in dose of current opioid

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T H E PA I N P R AC T I T I O N E R

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29

TW O SOURCES

OF PAIN

O NE SOURCE OF RELIEF

NUCYNTA® ER is the first and only FDA-approved long-acting opioid designed to control both nociceptive pain and the neuropathic pain associated with diabetic peripheral neuropathy (DPN).

NUCYNTA® ER is an opioid agonist indicated for the management of: • pain severe enough to require daily, around-theclock, long-term opioid treatment and for which alternative treatment options are inadequate

Not an actual patient.

• neuropathic pain associated with diabetic peripheral neuropathy (DPN) in adults severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate Limitations of Use • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve NUCYNTA® ER for use in patients for whom alternative treatment options (e.g., nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain • NUCYNTA® ER is not indicated as an as-needed (prn) analgesic

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

TIME TO DUAL

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

COVERED FOR

94%

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

• Administer NUCYNTA® ER ~q12h3

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

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and INTERACTION WITH ALCOHOL See full prescribing information for complete boxed warning.

• NUCYNTA® ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow NUCYNTA® ER tablets whole to avoid exposure to a potentially fatal dose of tapentadol. (5.2) • Accidental ingestion of NUCYNTA® ER, especially in children, can result in fatal overdose of tapentadol. (5.2) • Prolonged use of NUCYNTA® ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. (5.3) • Instruct patients not to consume alcohol or any products containing alcohol while taking NUCYNTA® ER because co-ingestion can result in fatal plasma tapentadol levels. (5.4) CONTRAINDICATIONS: Significant respiratory depression; acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment; known or suspected paralytic ileus; hypersensitivity (e.g., anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product; concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days. *Please see full Prescribing Information for DOSAGE AND ADMINISTRATION. †Some restrictions and limitations apply. See full terms and conditions available at NUCYNTA.com. Available to commercially insured and cash-paying patients only. Patients covered by Medicare, Medicaid, or any other state- or federally funded benefit program are excluded. Patients must be 18 years of age or older. This promotion cannot be combined with any other programs, offers, or discounts. Depomed reserves the right to rescind, revoke, or amend this offer without further notice. ‡Source: MMIT 2.0, May 2015.

References: 1. Buynak R, Shapiro DY, Okamoto A, et al. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase Ill study. Expert Opin Pharmocother. 2010;11(11):17871804. 2. Schwartz S, Etropolski M, Shapiro DY, et al. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011;27(1):151-162. 3. NUCYNTA® ER [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2014.

NUCYNTA® ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) WARNINGS AND PRECAUTIONS: Addiction, Abuse, and Misuse: NUCYNTA® ER contains tapentadol, an opioid agonist and a Schedule II controlled substance that can be abused in a manner similar to other opioid agonists, legal or illicit. There is a greater risk for overdose and death due to the larger amount of tapentadol present in NUCYNTA® ER. Assess risk for opioid abuse or addiction prior to prescribing NUCYNTA® ER. Addiction can occur in patients appropriately prescribed NUCYNTA® ER at recommended doses; in those who obtain the drug illicitly; and if the drug is misused or abused.

Therefore, routinely monitor for signs of misuse, abuse, and addiction. Patients at increased risk (e.g., patients with a personal or family history of substance abuse or mental illness) may be prescribed NUCYNTA® ER, but use in such patients necessitates intensive counseling about the risks and proper use along with intensive monitoring for signs of addiction, abuse, and misuse.

Life-threatening Respiratory Depression: Can occur at any time during the use of NUCYNTA® ER even when used as recommended.

Respiratory depression from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. To reduce the risk of respiratory depression, proper dosing and titration are essential. Overestimating the dose when converting patients from another opioid product can result in fatal overdose with the first dose. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status.

Neonatal Opioid Withdrawal Syndrome: Prolonged use of NUCYNTA® ER during pregnancy can result in withdrawal signs in the neonate, which may be life-threatening and require management according to protocols developed by neonatology experts. Neonatal opioid withdrawal syndrome presents as poor feeding, irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, rigidity, seizures, vomiting, diarrhea, and failure to gain weight.

Interactions With Central Nervous System Depressants: Hypotension, profound sedation, coma, respiratory depression, and death may result if NUCYNTA® ER is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, tranquilizers, general anesthetics, neuroleptics, other opioids). When considering the use of NUCYNTA® ER in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. If the decision to begin NUCYNTA® ER is made, start with NUCYNTA® ER 50 mg every 12 hours, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant.

Use in Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance. Because elderly patients are more likely to have decreased renal and hepatic function, consideration should be given to starting elderly patients in the lower range of recommended doses.

Closely monitor these patients, particularly when initiating and titrating NUCYNTA® ER and when given concomitantly with other drugs that depress respiration.

Use in Patients With Chronic Pulmonary Disease: Patients with significant chronic obstructive pulmonary disease or cor pulmonale and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or pre-existing respiratory depression, should be monitored for respiratory depression particularly when initiating therapy and titrating with NUCYNTA® ER. Consider the use of alternative nonopioid analgesics in these patients.

Hypotensive Effect: May cause severe hypotension. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor for signs of hypotension during dose initiation or titration.

Avoid use in patients with circulatory shock; may cause vasodilation that can further reduce cardiac output and blood pressure.

Use in Patients With Head Injury or Increased Intracranial Pressure: Monitor patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy. NUCYNTA® ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure.

Opioids may also obscure the clinical course in a patient with a head injury.

Seizures: May aggravate convulsions in patients with convulsive disorders and may induce or aggravate seizures. Monitor patients with a history of seizure disorders for worsened seizure control during therapy.

Serotonin Syndrome: Cases of life-threatening serotonin syndrome have been reported with the concurrent use of NUCYNTA® ER and serotonergic drugs. Serotonergic drugs comprise selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, drugs that affect the serotonergic neurotransmitter system, and drugs that impair metabolism of serotonin (including MAOIs). This may occur within the recommended dose. Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g.,

tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) and can be fatal. If concomitant treatment with SSRIs, SNRIs, TCAs, or triptans is clinically warranted, careful observation of the patient is advised, particularly when initiating or titrating the dose.

Use in Patients With Gastrointestinal (GI) Conditions: Contraindicated in patients with Gl obstruction including paralytic ileus; may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

Avoidance of Withdrawal: Withdrawal symptoms (e.g., anxiety, sweating, insomnia, restlessness, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection) may occur: • After abrupt discontinuation or a significant dose reduction of NUCYNTA® ER in physically dependent patients. When discontinuing NUCYNTA® ER, gradually taper the dose.

• If mixed agonist/antagonist (e.g., butorphanol, nalbuphine, pentazocine) and partial agonist (e.g., buprenorphine) analgesics are used in patients who have received or are receiving NUCYNTA® ER. Avoid use with mixed agonists/ antagonists and partial agonists.

• If opioid antagonists (e.g., naloxone, nalmefene) are administered in physically dependent patients. Administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.

Driving and Operating Heavy Machinery: May impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA® ER and know how they will react to the medication.

Hepatic Impairment: Avoid use in patients with severe hepatic impairment (Child-Pugh Score 10 to 15). In patients with moderate hepatic impairment (Child-Pugh Score 7-9), initiate treatment with NUCYNTA® ER 50 mg no more than once every 24 hours, with a maximum dose of 100 mg per day.

Monitor for respiratory and CNS depression when initiating and titrating NUCYNTA® ER. Renal Impairment: Use in patients with severe renal impairment (CLCR <30 mL/min) is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

DRUG INTERACTIONS Alcohol: See BOXED WARNING. Muscle Relaxants: Monitor patients receiving muscle relaxants and NUCYNTA® ER for signs of respiratory depression that may be greater than otherwise expected. Tapentadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

Anticholinergics: Use with anticholinergic products may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

USE IN SPECIFIC POPULATIONS Pregnancy/Nursing Mothers: Pregnancy Category C. NUCYNTA® ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms. Observe newborns for symptoms of neonatal opioid withdrawal syndrome. Withdrawal symptoms can occur in breast-feeding infants when maternal administration of NUCYNTA® ER is stopped.

Labor and Delivery: Opioids cross the placenta and may produce respiratory depression in neonates. NUCYNTA® ER is not for use in women during and immediately prior to labor, when shorter-acting analgesics or other analgesic techniques are more appropriate.

Use in Elderly, Renal Impairment, and Hepatic Impairment: See WARNINGS AND PRECAUTIONS. DRUG ABUSE AND DEPENDENCE: See BOXED WARNING OVERDOSAGE: Institute supportive measures to manage respiratory depression, circulatory shock, and pulmonary edema as required. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression.

ADVERSE REACTIONS: In clinical studies, the most common (≥10%) adverse reactions were nausea, constipation, vomiting, dizziness, somnolence, and headache.

Select Postmarketing Adverse Reactions: Anaphylaxis, angioedema, and anaphylactic shock have been reported very rarely with ingredients contained in NUCYNTA® ER. Advise patients how to recognize such reactions and when to seek medical attention. Panic attack has also been reported.

Please see Brief Summary, including BOXED WARNING, on the following pages. © July 2015, Depomed, Inc. All rights reserved. APL-NUCX-0029 Rev.2

BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION This does not include all the information needed to use NUCYNTA® ER safely and effectively.

See full Prescribing Information for NUCYNTA® ER. INDICATIONS AND USAGE NUCYNTA® ER is indicated for the management of: • pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate • neuropathic pain associated with diabetic peripheral neuropathy (DPN) in adults severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

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

• NUCYNTA® ER is not indicated as an as-needed (prn) analgesic.

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; AND INTERACTION WITH ALCOHOL See full prescribing information for complete boxed warning.

• NUCYNTA® ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow NUCYNTA® ER tablets whole to avoid exposure to a potentially fatal dose of tapentadol. (5.2) • Accidental ingestion of NUCYNTA® ER, especially in children, can result in fatal overdose of tapentadol. (5.2) • Prolonged use of NUCYNTA® ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. (5.3) • Instruct patients not to consume alcohol or any products containing alcohol while taking NUCYNTA® ER because co-ingestion can result in fatal plasma tapentadol levels. (5.4) CONTRAINDICATIONS Significant respiratory depression; acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment; known or suspected paralytic ileus; hypersensitivity (e.g., anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product; concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days.

WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse: NUCYNTA® ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA® ER exposes users to the risks of addiction, abuse, and misuse. As modified-release products such as NUCYNTA® ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present.

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA® ER and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA® ER, and monitor all patients receiving NUCYNTA® ER for the development of these behaviors or conditions.

Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol addiction or abuse) or mental illness (e.g., major depression).The potential for these risks should not, however, prevent the prescribing of NUCYNTA® ER for the proper management of pain in any given patient. Patients at increased risk may be prescribed modified-release opioid formulations such as NUCYNTA® ER, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA® ER along with intensive monitoring for signs of addiction, abuse, and misuse.

Abuse or misuse of NUCYNTA® ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tapentadol and can result in overdose and death.

Opioid agonists such as NUCYNTA® ER are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA® ER. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression has been reported with the use of modified release opioids, even when used as recommended.

Respiratory depression from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA® ER, the risk is greatest during the initiation of therapy or following a dose increase.

Closely monitor patients for respiratory depression when initiating therapy with NUCYNTA® ER and following dose increases. To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA® ER are essential. Overestimating the NUCYNTA® ER dose when converting patients from another opioid product can result in fatal overdose with the first dose.

Accidental ingestion of even one dose of NUCYNTA® ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

Neonatal Opioid Withdrawal Syndrome: Prolonged use of NUCYNTA® ER during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.

Interactions with Central Nervous System Depressants: Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA® ER therapy. The co-ingestion of alcohol with NUCYNTA® ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol.

Hypotension, profound sedation, coma, respiratory depression, and death may result if NUCYNTA® ER is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids).

When considering the use of NUCYNTA® ER in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of alcohol or illicit drugs that cause CNS depression. If the decision to begin NUCYNTA® ER is made, start with NUCYNTA® ER 50 mg every 12 hours, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant.

Use in Elderly, Cachectic, and Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Therefore, closely monitor such patients, particularly when initiating and titrating NUCYNTA® ER and when NUCYNTA® ER is given concomitantly with other drugs that depress respiration.

Use in Patients with Chronic Pulmonary Disease: Monitor for respiratory depression those patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or pre-existing respiratory depression, particularly when initiating therapy and titrating with NUCYNTA® ER, as in these patients, even usual therapeutic doses of NUCYNTA® ER may decrease respiratory drive to the point of apnea.

Consider the use of alternative non-opioid analgesics in these patients if possible.

Hypotensive Effect: NUCYNTA® ER may cause severe hypotension. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressantdrugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dose of NUCYNTA® ER. In patients with circulatory shock, NUCYNTA® ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA® ER in patients with circulatory shock.

Use in Patients with Head Injury or Increased Intracranial Pressure: Monitor patients taking NUCYNTA® ER who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA® ER. NUCYNTA® ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury.

Avoid the use of NUCYNTA® ER in patients with impaired consciousness or coma.

Seizures: NUCYNTA® ER has not been evaluated in patients with a predisposition to a seizure disorder, and such patients were excluded from clinical studies. The active ingredient tapentadol in NUCYNTA® ER may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA® ER therapy.

Serotonin Syndrome: Cases of life-threatening serotonin syndrome have been reported with the concurrent use of tapentadol and serotonergic drugs. Serotonergic drugs comprise Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, drugs that affect the serotonergic neurotransmitter system (e.g. mirtazapine, trazodone, and tramadol), and drugs that impair metabolism of serotonin (including MAOIs). This may occur within the recommended dose. Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) and can be fatal.

Use in Patients with Gastrointestinal Conditions: NUCYNTA® ER is contraindicated in patients with GI obstruction, including paralytic ileus. The tapentadol in NUCYNTA® ER may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

Avoidance of Withdrawal: Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including NUCYNTA® ER. In these patients, mixed agonists/antagonists and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.

When discontinuing NUCYNTA® ER, gradually taper the dose.

Driving and Operating Heavy Machinery: NUCYNTA® ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.

Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA® ER and know how they will react to the medication.

Hepatic Impairment: A study with an immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA® ER in patients with severe hepatic impairment. Reduce the dose of NUCYNTA® ER in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when initiating and titrating NUCYNTA® ER. Renal Impairment: Use of NUCYNTA® ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: • Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] • Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3)] • Interaction with Other CNS Depressants [see Warnings and Precautions (5.4)] • Hypotensive Effects [see Warnings and Precautions (5.7)] • Gastrointestinal Effects [see Warnings and Precautions (5.11)] • Seizures [see Warnings and Precautions (5.9)] • Serotonin Syndrome [see Warnings and Precautions (5.10)] Clinical Trial Experience Commonly-Observed Adverse Reactions in Clinical Studies with NUCYNTA® ER in Patients with Chronic Pain due to Low Back Pain or Osteoarthritis The most common adverse reactions (reported by ≥10 % in any NUCYNTA® ER dose group) were: nausea, constipation, dizziness, headache, and somnolence.

The most common reasons for discontinuation due to adverse reactions in eight Phase 2/3 pooled studies reported by ≥1% in any NUCYNTA® ER dose group for NUCYNTA® ER- and placebo-treated patients were nausea (4 % vs. 1%), dizziness (3% vs. <1%), vomiting (3% vs. <1%), somnolence (2% vs. <1%), constipation (1% vs. <1%), headache (1% vs. <1%), and fatigue (1% vs. <1%), respectively.

Commonly-Observed Adverse Reactions in Clinical Studies with NUCYNTA® ER in Patients with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy The most commonly reported ADRs (incidence ≥ 10% in NUCYNTA® ER-treated subjects) were: nausea, constipation, vomiting, dizziness, somnolence, and headache.

Postmarketing Experience: The following adverse reactions, not above, have been identified during post approval use of tapentadol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Psychiatric disorders: hallucination, suicidal ideation, panic attack.

Anaphylaxis, angioedema, and anaphylactic shock have been reported very rarely with ingredients contained in NUCYNTA® ER. The psychiatric disorders end with panic attack. Advise patients how to recognize such reactions and when to seek medical attention.

DRUG INTERACTIONS Alcohol: Concomitant use of alcohol with NUCYNTA® ER can result in an increase of tapentadol plasma levels and potentially fatal overdose of tapentadol. Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while on NUCYNTA® ER therapy.

Monoamine Oxidase Inhibitors: NUCYNTA® ER is contraindicated in patients who are receiving monoamine oxidase inhibitors (MAOIs) or who have taken them within the last 14 days due to potential additive effects on norepinephrine levels, which may result in adverse cardiovascular events.

CNS Depressants: The concomitant use of NUCYNTA® ER with other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol can increase the risk of respiratory depression, profound sedation, coma and death. Monitor patients receiving CNS depressants and NUCYNTA® ER for signs of respiratory depression, sedation and hypotension.

When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced.

Serotonergic Drugs: There have been post-marketing reports of serotonin syndrome with the concomitant use of tapentadol and serotonergic drugs (e.g., SSRIs and SNRIs). Caution is advised when NUCYNTA® ER is coadministered with other drugs that may affect serotonergic neurotransmitter systems such as SSRIs, SNRIs, MAOIs, and triptans. If concomitant treatment of NUCYNTA® ER with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.

Muscle Relaxants: Tapentadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Monitor patients receiving muscle relaxants and NUCYNTA® ER for signs of respiratory depression that may be greater than otherwise expected.

Mixed Agonist/Antagonist Opioid Analgesics: Mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) and partial agonists (e.g., buprenorphine) may reduce the analgesic effect of NUCYNTA® ER or precipitate withdrawal symptoms. Avoid the use of mixed agonist/ antagonist analgesics in patients receiving NUCYNTA® ER. Anticholinergics: The use of NUCYNTA® ER with anticholinergic products may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

USE IN SPECIFIC POPULATIONS Pregnancy Clinical Considerations Fetal/neonatal adverse reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Observe newborns for symptoms of neonatal opioid withdrawal syndrome, such as poor feeding, diarrhea, irritability, tremor, rigidity, and seizures, and manage accordingly.

Teratogenic Effects - Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. NUCYNTA® ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery: Opioids cross the placenta and may produce respiratory depression in neonates. NUCYNTA® ER is not for use in women during and immediately prior to labor, when shorter acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor.

Nursing Mothers: There is insufficient/limited information on the excretion of tapentadol in human or animal breast milk. Physicochemical and available pharmacodynamic/toxicological data on tapentadol point to excretion in breast milk and risk to the breastfeeding child cannot be excluded.

Because of the potential for adverse reactions in nursing infants from NUCYNTA® ER, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Withdrawal symptoms can occur in breast-feeding infants when maternal administration of NUCYNTA® ER is stopped.

Pediatric Use: The safety and efficacy of NUCYNTA® ER in pediatric patients less than 18 years of age have not been established.

Geriatric Use: Of the total number of patients in Phase 2/3 double-blind, multiple-dose clinical studies of NUCYNTA® ER, 28% (1023/3613) were 65 years and over, while 7% (245/3613) were 75 years and over. No overall differences in effectiveness or tolerability were observed between these patients and younger patients.

In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. Because elderly patients are more likely to have decreased renal and hepatic function, consideration should be given to starting elderly patients with the lower range of recommended doses.

Renal Impairment: The safety and effectiveness of NUCYNTA® ER have not been established in patients with severe renal impairment (CLCR <30 mL/min). Use of NUCYNTA® ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

Hepatic Impairment: Administration of tapentadol resulted in higher exposures and serum levels of tapentadol in subjects with impaired hepatic function compared to subjects with normal hepatic function. The dose of NUCYNTA® ER should be reduced in patients with moderate hepatic impairment (Child-Pugh Score 7 to 9).

Use of NUCYNTA® ER is not recommended in severe hepatic impairment (Child-Pugh Score 10 to 15).

DRUG ABUSE AND DEPENDENCE Controlled Substance: NUCYNTA® ER contains tapentadol, a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone. NUCYNTA® ER can be abused and is subject to misuse, addiction, and criminal diversion. The high drug content in the extended release formulation adds to the risk of adverse outcomes from abuse and misuse.

Abuse: All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited to the following examples: the use of a prescription or over-the-counter drug to get “high,” or the use of steroids for performance enhancement and muscle build up.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and include: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

“Drug-seeking” behavior is very common to addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated claims of loss of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers, and people suffering from untreated addiction. Preoccupation with achieving pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.

NUCYNTA® ER, like other opioids, can be diverted for non-medical use into illicit channels of distribution.

Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Dependence: Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

NUCYNTA® ER should not be abruptly discontinued. If NUCYNTA® ER is abruptly discontinued in a physically-dependent patient, an abstinence syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms.

OVERDOSAGE Clinical Presentation: Acute overdosage with opioids can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and sometimes pulmonary edema, bradycardia, hypotension and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations.

Treatment of Overdose: In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques.

Rx Only

© 2015 Depomed, Inc., Newark, CA 94560 USA NUCYNTA® ER is a registered trademark of Depomed, Inc. All rights reserved.APL-NUCX-0041 Rev.2

ACPP UPdAte

New Clinical Skills Cohort Model a Success

By Lou CLark, MFa, PhD, ProjeCt Manager

B

eginning with this yearâ&#x20AC;&#x2122;s meeting, the clinical skills assessment portion of the Academy Advanced Credentialed Pain Practitioner (ACPP) has been changed to a cohort model from an individual practitioner assessment. The clinical assessment uses an Objective Structured Clinical Examination (OSCE) format, which over the last 20 years has become the industry standard in assessing the development of clinical and communication skills for medical students and other health care trainees across the United States and internationally.

While the Pain Skills OSCE is modeled on this form of assessment, it serves a related but different purpose.

Our OSCE is not an examination in the official sense, but rather it is intended as a formative, continuing education opportunity. In administering the Lou Clark Pain Skills OSCE we strive to encourage (left) and the licensed physicians to self-reflect on roustandardized patient actors tine practices, gain skill-based feedback

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| T H E PA I N P R AC T I T I O N E R | W I N T E R 2 0 1 5

from experts in the field, and dialogue with colleagues about the challenges and rewards of practicing pain management.

In the vein of demystifying the process for our members who may be interested in this program but have not yet participated, I offer some details about the development of the Pain Skills OSCE. Prior to this program getting underway at the 2014 annual meeting in Phoenix, a team of content and assessment experts joined Academy staff members to create the OSCE curriculum and logistical event plans over the course of a year. Advance planning for any OSCE is especially important to ensure that all participants receive maximum benefit from this educational experience. George D. Comerci, Jr., MD, Brian Shelley, MD, and Daniel Duhigg, DO, from the University of New Mexico School of Medicine, led the curriculum development to ensure that the three standardized patient cases presented in the OSCE were relevant and reflective of pain patients regularly seen by Academy members. Additionally, this team, joined by Nancy Schneider and me as medical education assessment consultants, created evaluation materials in keeping with the standardized patient cases. These evaluation materials constitute multiple modalities of feedback comprising a written self-reflection form completed by participants; skill-based verbal feedback from our three lead physicians (Comerci, Shelley, and Duhigg) on case-specific clinical checklists; and patient-centered verbal feedback specific to communication skills from

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trained standardized patient actors. All of the standardized patient actors are trained for this event to specifically portray physical, emotional, and communicative aspects of patients with chronic pain and are also selected for their ability to provide constructive feedback to participants.

Following our curriculum development, we have continued to modify our logistical event plan to provide the best experience for our participants. In 2014 members who participated in this event each completed all three of the standardized patient cases in a dedicated clinical skills center that was off-site from the annual meeting. While this was a great foundation in terms of launching the program, in 2015 we introduced our new cohort model in which three physicians move through the OSCE as a team. Each physician takes the lead on one of the three cases, while the other two team members observe and provide peer feedback and support.

The 30 participants who completed the Pain Skills OSCE at the 2015 annual meeting said that they loved the cohort model, and we are very excited to be moving forward with this design for the 2016 annual meeting in San Antonio. Participants explained that in addition to the expert feedback and authentic portrayals from the stan-

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dardized patients, one of the best benefits of the cohort model was having the opportunity to observe physicians trained in other specialties interviewing and examining patients. This promoted vibrant dialogue between participants in which they exchanged techniques and perspectives they would not normally have in the course of routine practice, which is often alone. Additionally, the fact that we have transitioned this program from off-site to on-site makes it more accessible to all annual meeting attendees.

Holding the OSCE in hotel conference rooms also provided a more relaxed atmosphere in which to participate, allowing participants to enjoy and find value in this unique educational experience.

Beginning in 2016, anyone who has passed the ACPP written exam must register for the OSCE at the annual meeting in San Antonio in order to earn the Advanced Credential. Eligible candidates will be contacted by the Academy and given a schedule before the event.

On the day of the OSCE, participants arrive at the registration area 30 minutes prior to the start of the event for an orientation that will maximize their benefit for this program. In this orientation, participants learn about the logistics and flow of the event and meet the two other

physicians who will be participating with them in the program. Each team will participate in three cases. Each participant conducts a 20-minute interview and physical exam of a standardized patient. While 20 minutes may not seem like a lot of time, I assure you that for our intended purposes it works. The object for our participants is to do focused physical exams so that they can concentrate on eliciting the pain story from the patient. Our goal is to support each participant in refining this crucial element of the medical encounter.

Following each encounter all involved (participants, cohort peers, faculty experts, and standardized patients) spend five minutes preparing feedback. Then, there is a 10-minute case-specific feedback session in which all parties talk about how they experienced the encounter. The entire program takes approximately three hours for each participant and cohort to complete. Following completion, we hold informal participant debriefs.

The debrief sessions have become a favorite aspect of mine for this event. As a non-clinician I have had the privilege of learning more about the practice of pain management. Over cups of coffee I have heard participants share accounts of the rewards of not giving up on patients who,

at first, seemed outside the scope of their care. I have felt humbled in discovering the physical risks participants take daily in working with frustrated and angry patients. I have come to appreciate pain management as an interdisciplinary field that is informed by a variety of clinical perspectives. As I am a communication scholar, I especially appreciate participant exchanges focused on how experiencing this event has reminded them that constructive communication between providers and patients is at the heart of medical practice. In the words of one participant, what he loved about the Pain Skills OSCE is that it â&#x20AC;&#x153;helped me get back to the basics.â&#x20AC;? In other words, this event provides time and space to consider, develop, and return to foundational communication and clinical skills. Thanks for taking the time to read a bit more about this program. I hope to have the opportunity to meet you and hear your thoughts in San Antonio!

Lou Clark, PhD, is an Assistant Professor in the School of Medicine and director of clinical Skills at uniformed Services university of the health Sciences. She studies issues linked to clinical communication including grief and compassion in health-related organizations. She also consults with medical educators in designing and delivering simulated educational experiences for health care trainees and practitioners. She is the project manager for the AAPM Pain Skills oSce.

T H E PA I N P R AC T I T I O N E R

| VOLUME 25, NUMBER 4 |

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FROM THE CLINIC

Autologous Stem Cell Therapy A NATuropAThiC ApproACh for The TreATmeNT of ChroNiC muSCuloSkeleTAl pAiN CoNdiTioNS—part ll of ll Harry adelson, nd

Part I of this series, published in the Fall 2015 issue of The Pain Practitioner, provided an overview of the fundamental methods employed by the naturopathic physician for laying a foundation of optimal cellular metabolism, connective tissue health, and overall function in order to optimize stem cell therapy. Part II details the methods for harvest and concentration/ isolation of bone marrow aspirate concentrate (BMAC) and adipose-derived stromal vascular fraction (SVF) and includes original research comparing three arms treating low back pain and osteoarthritis of the knee: 1) the use of bone marrow aspirate concentrate (BMAC) alone; 2) the use of adipose-derived stromal vascular fraction suspended in platelet rich plasma (SVF/PRP); and 3) the use of adipose-derived stromal vascular fraction suspended in BMAC (SVF/BMAC).

Summary

An emerging approach to the treatment of chronic musculoskeletal pain is the use of autologous mesenchymal stem cells (MSCs) harvested from a patient’s own bone marrow or adipose tissue for reinjection into damaged or degenerated joints, ligaments, tendons, and muscles. The purpose of this retrospective survey was to compare patient-reported outcomes after treatment of osteoarthritis of the knee or low back pain in three treatment groups: patients injected with bone marrow aspirate concentrate (BMAC), patients injected with adipose-derived stromal vascular fraction suspended in platelet rich plasma (SVF/PRP), and patients injected with adipose-derived stromal vascular fraction suspended in bone marrow aspirate concentrate (SVF/BMAC).

Based on patient reports, patients injected with BMAC had consistently satisfactory results, patients injected with SVF/ PRP either had results superior to BMAC or no improvement at all, and patients injected with SVF/BMAC had consistently satisfactory results superior to BMAC alone.

There were no adverse outcomes in any patient surveyed (N = 95). Based on these results, injection of SVF/BMAC for osteoarthritis of the knee and low back pain appears to be safe and produces consistently satisfactory results.

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Introduction

Mesenchymal stem cells (MSCs) have been dubbed “patient-specific drug stores for injured tissues” because of their ability to secrete bioactive factors and signals at variable concentrations in response to local microenvironmental cues (1). MSCs are found throughout the body in many tissue types, but they are particularly abundant and easily harvested from the medullary cavity of flat bones and from adipose tissue (2,3). MSCs can be easily concentrated from bone marrow with simple centrifugation. With slightly more effort, MSCs can be isolated from adipose tissue through a multistep process of incubation/enzymatic digestion with collagenase followed by centrifugation and filtration. When injected into the site of damage or degeneration, MSCs release a spectrum of antiinflammatory, immunomodulatory, and trophic factors that trigger the regeneration and healing of connective tissues through activation of stem cells endogenous to the site.

As the pool of data continues to grow, the site-specific injection of autologous stem cells has shown promise in musculoskeletal pain conditions such as osteoarthritis (4), sports or traumatic injury (5), low back and discogenic pain (6), neck pain with or without cervicogenic headaches (7), and osteonecrosis (8). Of note, concurrent bodies of data continue to grow that appear to refute the validity of arthroscopic surgery for knee pain (9-11) and cast doubt upon the validity of steroid epidural injections for low back pain (12,13).

Currently in the United States there are a growing number of pain clinics offering autologous stem cell therapy to patients suffering with musculoskeletal pain conditions.

Based on rudimentary internet searches and my own familiarity with the industry, the majority of clinics that offer autologous stem cell therapy offer either BMAC or SVF/ PRP, while significantly fewer clinics offer both. According to their websites, clinics offering BMAC often claim bone marrow-derived stem cells to be superior because of the greater body of data supporting their use. Clinics offering SVF/PRP often claim adipose derived stem cells to be superior because of the much larger total MSC count produced

FROM THE CLINIC

Figure 1 Bone marrow aspiration from the iliac crest.

compared to BMAC. I am not aware of any studies directly comparing bone marrow-derived stem cells to adipose-derived stem cells and have seen no data evaluating the combination of the two (SVF/BMAC) in a single treatment.

The purpose of this retrospective survey was to compare patient-reported outcomes after treatment of osteoarthritis of the knee and low back pain in three treatment groups: patients injected with BMAC, patients injected with SVF/ PRP, and patients injected with SVF/BMAC. Methods

Patients presenting to Docere Clinics in Park City, Utah, between July 15, 2014, and November 15, 2014, who were deemed candidates for autologous stem cell therapy, were asked to choose between being treated with BMAC or SVF/ PRP. The conversation can be summarized as follows: “I can do a bone marrow aspiration and treat you with BMAC, with which I have five years of experience and am aware of data supporting its use, or I can do a lipoaspiration and a blood draw and treat you with SVF suspended in PRP, which has the potential to provide us with a far greater yield of stem cells and, theoretically, a superior outcome.

However I have little experience with it and there are very few data supporting its use.” Patients then self-selected into the BMAC or the SVF/PRP group.

Patients treated with BMAC underwent a fluoroscopically guided bone marrow aspiration of 40 to 120 mL from a single puncture at the site of the iliac crest. The puncture was made on the thickest part of the posterior superior iliac spine. The needle was oriented to be parallel to the flat bone,

Figure 2 Fluoroscopically guided, intraarticular injection of the knee.

and was rotated 90 degrees and advanced 0.5 cm after every 10 mL of marrow aspirated (Figure 1). The marrow was then centrifuged for 10 minutes at 1,000 g and the buffy coat drawn into one or more 10 mL treatment syringes.

In patients treated with SVF/PRP, 100 mL Figure 3 of adipose tissue, 50 mL ultrasound-guided injection of MCL. per side, was aspirated from the flank region and 40 mL to 120 mL of venous blood was drawn. In order to isolate SVF, the adipose tissue was incubated and enzymatically digested with collagenase, then centrifuged and filtered (the entire process took approximately 45 minutes).

The blood was centrifuged for 10 minutes at 1,000 g and concentrated in a “pure,” or “acellular” manner (devoid of RBCs or WBCs). SVF was suspended in one or more 10 mL syringes of PRP. Patients treated for osteoarthritis of the knee received a fluoroscopically guided, intra-articular injection into the knee (Figure 2). Ultrasound guidance was added for patients who reported pain on palpation to the medial collateral and lateral collateral ligament or supra/infra-patellar tendon (Figure 3).

Patients treated for low back pain received fluoroscopically guided injections bilaterally at the following locations, T H E PA I N P R AC T I T I O N E R

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FROM THE CLINIC

FiguRe 4 Lumbar transforaminal epidurals with stem cells.

FiguRe 5 injection of stem cells into intervertebral discs

2 mL of injectate per location: perifacet at L2/3-L5/S1 levels, and iliolumbar ligament, proximal and distal insertions, and the sacroiliac ligament, in three locations. Patients reporting radiculopathy/paresthesia received additional lumbar transforaminal epidural injections of 5 mL of stem cells (Figure 4). Intradiscal injections of 1.5 mL stem cells were given to patients who reported mid-line pain that worsened when bending forward and whose MRIs showed desiccation (Figures 5).

Patients who had experienced pain for a minimum of one year prior to treatment were asked to rate their percentage of improvement on a numerical scale and whether they experienced any adverse effects from treatment.

During this period and during preliminary follow-up with patients, I began to notice a trend that many SVF/ PRP patients reported higher satisfaction than those in the BMAC group, but the remainder were experiencing no improvement at all. Beginning November 16, 2014, I began offering patients SVF prepared as described above but suspended in BMAC rather than PRP, hypothesizing that the combination could offer the consistency of BMAC with the augmented outcomes of SVF. On August 1, 2015, we reviewed the charts of all patients with knee arthritis and low back pain who were treated with SVF/BMAC between November 15, 2014, and March 15, 2015, to identify those who had experienced pain for a minimum of one year prior to treatment.

They were asked to rate their percentage of improvement on a numerical scale and whether they experienced any adverse effects from treatment.

Results

Results (Table) were consistent between the two BMAC groups. The average improvement reported in the knee 42

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osteoarthritis group (n = 21) was 75.7%. One patient reported only 10% improvement; the remainder reported 50% or better improvement. In the low back pain group (n = 9), the average improvement was 70.6%. Only one patient reported no improvement at all, and everyone else reported 50% or better improvement.

Results were also consistent between the two SVF/PRP groups. The average improvement reported in the knee osteoarthritis group (n = 26) was 61.7% and in the low back pain group (n = 14) the average improvement reported was 61.1%. However, in each group, there was a relatively higher percentage of patients who did not respond to treatment (26.9% and 28.6%, respectively). Patients who did respond to treatment improved, on average, more than those in the BMAC groups. Among responders, 84.5% of patients with knee osteoarthritis reported improvement and 85.5% of those with low back pain reported improvement.

Results were consistent between the two SVF/BMAC groups. In the SVF/BMAC:OA knees group (n = 14), one patient reported no improvement at all but everyone else reported 75% or better improvement resulting in an average of 81.5% improvement. In the BMAC:OA low back pain group (n = 11), one patient also reported no improvement but everyone else reported 80% or better improvement resulting in an average of 80.9% improvement.

None of the patients surveyed (N = 95) experienced complications or adverse reactions other than mild postprocedure soreness.

Discussion

Based on patient reports, patients injected with BMAC had consistently satisfactory results, patients injected with SVF/ PRP either had results superior to BMAC or no improvement at all, and patients injected with SVF/BMAC had con-

FROM THE CLINIC

TABLE Treatment Results for Autologous Stem Cell Therapy Options

Number of patients

BMAC: OA knee

BMAC: LBP

SVF/PRP: OA knee

SVF/PRP: LBP

SVF/BMAC: OA knee

SVF/BMAC: LBP

21

9

26

14

14

11

Male/female ratio

13 to 8

6 to 3

16 to 10

8 to 6

9 to 5

7 to 4

Age range/avg

35-83/60

29-76/45.7

38-85/63.7

38-71/58.9

44-81/59.5

39-73/54.8

BMI range/ave

21.954.8/26.9

21.3-31/23.9 19.9-39.1/27.0 23.2-35.4/27.2

21.6-29.3/25.6

20-32.2/25.4

Avg number of treatments

1.1

1.3

1

1

1.1

1

Avg % satisfaction (total)

75.70

70.60

61.70

61.10

81.50

80.90

Number of nonresponders (%)

0

1(11.1)

7(26.9)

4(28.6)

1(7.1)

1(9.1)

Avg % satisfaction (responders)

75.70

79.39

84.50

85.50

87.65

89.0

sistently satisfactory results superior to BMAC alone. There were no adverse outcomes in any patient surveyed (N = 95).

These results caused me to question what was responsible for the high non-responder rate in the SVF/PRP groups. It appears that for those who responded, SVF/PRP rendered a superior outcome to BMAC in both the OA knee and lower back pain groups; however, nearly 30% of the SVF/PRP patients treated had no benefit at all. An analysis of results from responders only in all the groups confirmed that the SVF/BMAC recipients had consistently satisfactory results superior to BMAC and SVF/PRP alone.

It is entirely possible that the MSCs did not survive the isolation process in the non-responder groups, which would account for the high percentage of nonresponders in the SVF/PRP group. A major flaw in the study is that flow cytometry was not performed to determine MSC total cell count and cell viability. I have since obtained a flow cytometer and I am measuring cell count and cell viability in all patients treated with stem cell therapy. Future study will compare total cell count and cell viability to patientreported outcomes.

Based on these results, injection of SVF/BMAC for osteoarthritis of the knee and low back pain appears to be safe and produces consistently satisfactory results.

Clearly, this series of simple surveys does not claim to provide any hard evidence; it is merely intended as an empirical report of one clinician’s experience in this new and rapidly growing field.

References 1.

Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally respon-

2.

3.

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5.

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7.

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11.

12.

13.

MAC = Bone marrow aspirate concentrate SVF/PRP = Adipose-derived stromal vascular fraction suspended in platelet-rich plasma SVF/BMAC = Adipose-derived stromal vascular fraction suspended in bone marrow aspirate concentrate

sive therapeutics for regenerative medicine. Exp Mol Med. 2013; 45:e54. doi:10.1038/ emm.2013.94.

Hendrich C, Engelmaier F, Waertel G, Krebs R, Jäger M. Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients.

Orthop Rev (Pavia). 2009 Oct 10; 1(2):e32.

Michalek J, Moster R, Lukac L, et al. Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis. Cell Transplant. 2015 Jan 20.

Goldberg, VM. Stem cells in osteoarthritis. HSS J. 2012 Feb;8(1):59-61.

Quintero AJ, Wright VJ, Fu FH, Huard J. Stem cells for the treatment of skeletal muscle injury. Clin Sports Med. 2009;28(1):1-11.

Orozco L, Soler R, Morera C, Alberca M, Sánchez A, García-Sancho J. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation. 2011 Oct 15;92(7):822-828.

Adelson H. Bone marrow and adipose derived autologous stem cells for the treatment of chronic musculoskeletal pain. Paper presented at Annual Meeting of the American Academy of Pain Management; September 2014; Phoenix, Arizona.

Pak J. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series. J Med Case Rep. 2011 Jul 7;5:296.

Thorlund JB, Juhl CB, Roos EM, Lohmander LS. Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms. Br J Sports Med. 2015 Oct;49(19):1229-35.

Moseley JB1, O’Malley K, Petersen NJ, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N EnglJ Med. 2002;347(2):81-88.

Kirkley A, Birmingham TB, Litchfield RB, et al. A randomized trial of arthroscopic surgery for osteoarthritis of the knee. N EnglJ Med. 2008;359(11):1097-1107.

Radcliff K, Kepler C, Hilibrand A, et al. Epidural steroid injections are associated with less improvement in the treatment of lumbar spinal stenosis: a subgroup analysis of the Spine Patients Outcomes Research Trial. Spine (Phila Pa 1976). 2013 Feb 15;38(4):279-91.

Pinto RZ, Maher CG, Ferreira ML, et al. Epidural corticosteroid injections in the management of sciatica: a systematic review and meta-analysis. Ann Intern Med. 2012 Dec 18;157(12):865-77.

Harry Adelson, ND, opened Docere Clinics in Salt Lake City in 2002, and from day one his practice has been 100% regenerative injection therapies for the treatment of musculoskeletal pain conditions. In 2006 he incorporated platelet rich plasma and ultrasoundguided injection into his armamentarium; in 2010, bone marrow aspirate concentrate and adiposederived stem cells; and in 2013, fluoroscopic-guided injection. Since February of 2010, Dr. Adelson has performed more than 3,000 bone marrow and adipose-derived adult stem cell procedures, placing him in the company of those most experienced in the world with use of autologous stem cells for the treatment of musculoskeletal pain conditions.

T H E PA I N P R AC T I T I O N E R

| VOLUME 25 NUMBER 4 |

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COMMENTARY

Modulating Pain Signal tranSMiSSion:

How targeted nervous System regulation Can Manage Pain Without Side Effects

By Pe ter Behel , M A , BCB

ApART fRom ThE oNgoINg efforts involved in developing increasingly sophisticated methods of blocking pain receptor sites pharmaceutically, very little attention has been paid to modifying pain signal transmission internally, based on modulating the mechanisms involved with pain signal conduction. This is a glaring and costly omission, as it turns out. over the years my experience has demonstrated that regulating pain signal transmission can be as fundamental as learning how to adjust the throttle on a boat or an airplane. All thatâ&#x20AC;&#x2122;s required is the ability to post the requisite targets on a computer screen and the understanding of how to optimally influence their operation. The outcomes Iâ&#x20AC;&#x2122;ve observed in more than 13 years of facilitating hospital-based pain management programs have amounted to a substantial number of individuals who are grateful about having recovered lost levels of functioning and relieved at having minimized the need for costly pain interventions. from the outset of its recognition early in the 20th century, pain has been defined by its interaction with the operation of the autonomic nervous system (1). Indeed, the abiding sentiment among pioneering researchers was that pain was essentially manifested in the activities of the sympathetic division, to the extent that autonomic reflexes constituted the foundation of what came to be referred to as the nociceptive reaction. While the subsequent research of the past 100 years continues to shed light on the various processes involved with pain signal conduction, the fundamental role that the autonomic nervous system plays in pain signal transmission has remained virtually unchanged.

The idea that pain signal transmission possesses a degree of variability is nothing new. melzack and Wall demonstrated in 1965 that emotionally based influences directly impact an individualâ&#x20AC;&#x2122;s experience of pain, causing it to either increase or diminish (2). Concomitantly, various 44

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cortical structures associated with the limbic system are recognized as being involved in the pain-autonomic nervous system interaction.

The Neuronal Mechanisms of Emotionality

The amygdala, for example, has been associated with chronic, persistent pain levels via its modulation of affective states such as fear, anxiety, and depression (3), and amygdala plasticity has been directly linked with variations in pain behavior (4). moreover, during persistent pain episodes, the central nucleus of the amygdala (CeA) is thought to actively contribute to pain enhancement, or hyperalgesia (5).

As the primary cortex for the viscero-sensory system, the insula is involved in the subjective experience of pain, and has been associated with allodynia, or abnormal pain associated with innocuous stimuli (6). functional magnetic resonance imaging (fmRI) has revealed increased somatosensory cortex connectivity to the bilateral anterior insula that has been correlated with increased pain severity in fibromyalgia sufferers, but not in healthy controls (7).

The anterior cingulate cortex is another limbic area that plays a critical role in nociception that is directly connected with autonomic functions involved with arousal (8). In addition to maintaining broad connections with multiple areas of the central autonomic network, the anterior cingulate cortex plays a principal role in affective and motivational aspects of pain (9). generally speaking, the interactions that take place between the neural structures involved in pain sensation and autonomic control are regarded as being extensive (10), and this is certainly no less the case when it comes to chronic pain (11).

Acute vs. Persistent Pain

modulating the pain signal transmission process optimally

COMMENTARY

involves accounting for the distinction between acute and chronic pain signal transmission, because these processes are not facilitated in the same way, or even by the same apparatus. Simply put, acute pain signals are transmitted along the A-delta nociceptive fibers, while chronic pain signals are conducted along the C fiber nociceptors.

C fiber neurons exhibit longer somatic action potential durations, slower conduction velocities, and more negative membrane potentials than A-delta fibers (12). C fibers are additionally associated with sympathetic vasoconstriction, and early animal studies have determined that C fiber stimulation directly increases sympathetic discharge.

Perhaps more revealing, the molecular mechanism of spinal long term potentiation (LTP) at C fiber synapses in the spinal dorsal horn is considered a synaptic model of pathological pain capable of leading to lasting pain in humans, LTP referring to a common mechanism of memory storage in the central nervous system based on an increase in efficacy of synaptic transmission (13).

Inasmuch as the C fiber nociceptors make up the majority of sensory neurons in the peripheral nervous system, it is worth noting that their transmission separates into two specific classifications of nociception, peptidergic and nonpeptidergic (14). Peptidergic C fibers express pain-relevant neuropeptides and neurotransmitters such as substance P and calcitonin gene-related peptide (CGRP),

regulating pain signal transmission can be as fundamental as learning how to adjust the throttle on a boat.

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MODULATING PAIN SIGNAL TRANSMISSION

which are associated with neurogenic inflammation (15).

Pro-inflammatory neuropeptide secretion in peptidergic C-type nociceptors also facilitates rapid modulation of pain signaling that is linked with proalgesic sensitization of peripheral nociceptors (16).

Pain Amplification

Hyperalgesia, or pain elevation, has been found to be associated with autonomic nervous system dysfunction in fibromyalgia (17), and sympathetic hyperactivity has similarly been linked with somatic hyperalgesia in individuals suffering from irritable bowel syndrome (18). Increased sympathetic activity and hyperalgesia have also been associated in chronic pancreatitis (19), and the relationship between hyperalgesia and autonomic symptoms has likewise been recognized in complex regional pain syndrome (CRPS) (20), esophageal hyperalgesia (21), and Crohnâ&#x20AC;&#x2122;s disease, where autonomic dysfunction has been found to modulate visceral pain perception (22).

For that matter, chronic pain that responds to antisympathetic treatments is specifically referred to as sympathetically maintained pain (SMP), and along with exhibiting hypersensitivity to norepinephrine (NE), SMP-related autonomic disturbances have been found to facilitate spreading sensitization, allodynia, and neurogenic inflammation (23). Inflammation is also correlated with autonomic dysfunction in diabetes (24), and sympathetic nerve fibers appear to contribute to the peripheral and central sensitization that is common in advanced bone cancer pain (25).

The extent of sympathetic nervous system involvement in these conditions makes it virtually impossible to separate sympathetic activation from inflammation and pain amplification. Autonomic dysfunction is not incidental in the potentiation of chronic pain processes. It is an intrinsic feature of pain-related pathogenesis. Yet the pain management industry as a whole bypasses modulating pain signal transmission through targeted autonomic regulation at enormous cost to public well-being.

Irrespective of concerns about the potential for physical dependency and addiction, opioids remain one of the most frequently prescribed treatments for alT H E PA I N P R AC T I T I O N E R

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COMMENTARY

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Modulating Pain Signal tranSMiSSion

leviating moderate to severe chronic pain, despite the risk of complications due to polypharmacy, life-threatening respiratory depression, and neonatal risks involving birth defects. Moreover, pain sufferers who receive opioids to relieve their pain are susceptible to paradoxically become more sensitive to pain as a direct result of the opioid treatment itself (26).

Although better outcomes are recognized in chronic non-cancer pain when treatments incorporate functional strategies to improve pain (27), and non-opioid approaches are recommended in the World Health Organization’s analgesic ladder prior to resorting to chronic opioid therapy (COT) (28), in actual clinical practice adhering to the analgesic ladder’s recommended progression is unmonitored, and ultimately left up to the discretion of the prescribing specialist.

Pain-Autonomic Nervous System Interaction

To the extent that the autonomic nervous system is responsible for the conduction of pain signals, modulating autonomic output represents the lone chronic pain approach specifically geared to modify pain signaling where

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it is generated. When applied advantageously, autonomic regulation provides the means to make ongoing adjustments that ensure training objectives continue to be met over the course of the treatment.

This places targeted autonomic regulation in a unique position with respect to other modalities that are palliative in nature. Attempts to modify sympathetic nervous system activation by facilitating non-specific relaxation may or may not affect pain signal transmission for a variety of reasons. Palliative measures aren’t positioned to affect conditioned hyperactive response patterns that have become a reflexive mechanism in the pain perpetuation process.

Without monitoring and measuring sympathetic output it can be challenging to infer or verify how nervous system activation might be responding to any modality that is being administered, or how response patterns themselves might be modifying over time.

Historically, biofeedback has successfully been utilized to moderate pain-related health conditions for decades, and although recent efforts have emerged to expand the term to represent a wider range of applied methodology (29), when autonomic regulation is targeted specifically with modulating pain signal transmission, long-term beneficial results are typically achieved (30).

Studies in animal models of complex regional pain syndrome indicate that modifying sympathetic output can effectively be used to relieve pain (31). Considering the insufficiency of data supporting the long-term effectiveness of opioids in the treatment of chronic pain (32), perhaps the time has come to adjust common prescribing practices to prioritize the use of non-toxic chronic pain management modalities that pose no additional health risks, before resorting to more severe measures.

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References 1.

2.

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Peter Behel, MA, BCB, is a former President

of the Biofeedback Society of California and is currently on faculty at Sonoma State University.

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DEPARTMENT

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ClaSSiFiEd adS, adVErtiSing dirECtorY

ADVertISING DIreCtOry to AdVertiSe in the PAin PrActitioner, contAct SheilA Miller (209)533-9744, SMiller@AAPAinMAnAge.org

1st Providers Choice-Pain Management EMR IMS Pain Management Specific EMR www.1stproviderschoice.com 480-782-1116 COVER 4

Aeon Clinical Laboratories Toxicology, Pharmacogenomics, Cancer Genomics www.aeonclinical.com 678-276-8412 COVER 3

AIS PainCare Intrathecal Pain Medication PAGE 39

BioBack by Medolutions Lumbar Othosis www.BioBack.com 888-978-7999 PAGE 48

Depomed, Inc. Nucynta ER www.nucynta.com/ 510-744-8000 PAGES 30-35

Itelagen PainCare™ PAGE 29

LOCKMED Medical Products LOCKMED Home Medication Lock Box www.LOCKMED.com 888-458-2746 PAGE 46

Micro Format Tamper Resistant Rx Paper Products www.RxPaper.com 800-333-0549 PAGE 48

OPTP Pain education and therapy products www.optp.com 800-367-7393 PAGE 47

Purdue Pharma L.P. Hysingla™ ER www.Hysinglaer.com 203-588-8000 PAGES 8-12

Salix Pharmaceuticals, Inc. Relistor www.Relistor.com COVER 2, PAGE 1

Silver Hill Hospital Chronic Pain & Recovery Center www.silverhillhospital.org 866-542-4455 PAGE 3

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ClASSIFIeD ADS

to PlAce A clASSiFied AdVertiSeMent contAct SheilA Miller (209)533-9744, SMiller@AAPAinMAnAge.org

Pain ManagEMEnt PHYSiCian Reading Health System is a not-for-profit healthcare system that provides comprehensive acute care, post-acute rehabilitation, behavioral health, and occupational health services to the people of Berks County, Pennsylvania as well as adjoining counties. Reading Hospital, the nationally recognized flagship of the system, is licensed for 673 beds (709 system beds). It performs 19,000 surgical procedures per year and has one of the busiest emergency departments in the State with 135,000 visits per year.

This position offers the opportunity to join a growing service line. Position will include inpatient, outpatient, acute and chronic pain. You will interface and work closely with Hospitalist Services and 2 Nurse Practitioners designated for Pain Management to define and expand our Pain Management program this is a fantastic opportunity for an entrepreneurial physician to join and grow a practice.

The Medical Center offers residency programs in family medicine, internal medicine, obstetrics and gynecology, podiatry as well as a general surgery residency which is in affiliation with Philadelphia College of Osteopathic Medicine.

Affiliations also exist with Pennsylvania State University, Temple University and the University of Pennsylvania. Reading supports graduate and undergraduate medical education through an affiliation with Thomas Jefferson University and Jefferson Medical College and other prestigious university medical schools.

Committed to educating a range of healthcare professionals, Reading’s School of Health Sciences offers programs in Nursing, Clinical Pastoral Education, Paramedic Education, Radiologic Technology and Surgical Technology. In addition, there is a School of Clinical Laboratory Science.

Education, cultural and recreational activities are major forces in Berks County.

There are five colleges and universities in the county and 18 public school districts. The Reading Symphony Orchestra and the Reading Public Museum are considered among the best in the state. In addition, the Berks Arts Council presents the largest jazz festival on the East Coast. For sports fans, there’s Reading Phillies baseball, the Royals Professional Hockey Club, the Reading Express (Arena Football League) and the brand new Reading Railers (minor league basketball). The picturesque countryside of Berks County provides many recreational opportunities. The Nolde Environmental Center and the Hawk Mountain Sanctuary provide unique educational opportunities, as well as the chance to enjoy the beauty of nature. We are within driving distance and close proximity to Philadelphia, Washington/Baltimore and New York City. In addition, the beautiful beaches of New Jersey, Delaware and Maryland are close and easily accessible.

For further information, contact: Beth A. Calabria, Manager, Medical Staff Recruitment Beth.calabria@readinghealth.org/484.628.6714 www.readinghealth.org

tMJ/SlEEP PraCtiCE For SalE in Front rangE, Co (CO 1406) Annual Revenues of $527K, 3 ops, 1800 sq. ft., 4 days per week, doctor retiring but willing to stay as mentor after sale. ADS Precise Consultants, frontdesk@adsprecise.com, 800-307-2537, www.adsprecise.com

DEPARTMENT

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classifieD aDs, aDvertising Directory

practices wanteD: pain management, pm&r, &pt

seeKing be/bc pain management specialist in roanoKe, va

Considering Selling your Practice? We are seeking practices on behalf of qualified buyers. Flexible deal structure, all-cash, with favorable terms.

Option for sellers to remain post-sale as employed providers.

Contact: Mo Majdi 800-416-2055 http://TransitionConsultants.com

Carilion Clinic, a physician-led multi-specialty clinic based in Roanoke, VA has an excellent employed opportunity for a BE/BC Pain Management Specialist to join our comprehensive interdisciplinary pain service, working directly with the Section(s) Physical Medicine and Rehabilitation, Neurosciences and Orthopaedics to deliver full scope, team-oriented Pain Management Services for acute pain in a primarily outpatient setting. Collaborate services for chronic pain with 150+ primary care physicians with support from Carilion Roanoke Memorial Hospital, modern 700-bed academic/tertiary referral medical center with Level I Trauma Services. Applicants are preferred to be fellowship trained in Pain Management with proven leadership experience. Candidates must be skilled with radiofrequency and interventional modalities including intrathecal delivery systems, spinal cord stimulators, and ESI. Carilion Clinic is the largest not-for-profit integrated health system serving nearly one million people in Western Virginia, with 7 hospitals, 220+ physician practice locations, and 24 GME programs. This network of 650+ multi-specialty physicians in over 60 specialties offers Carilion physicians faster access to patient information and history with a sophisticated, fully integrated electronic medical record system (EPIC) and excellent access to subspecialty consultation.

Roanoke is a metro area of over 300,000, located at the southern tip of Virginia’s spectacularly beautiful Shenandoah Valley, surrounded by the Blue Ridge Mountains and close to the 22,000 acre Smith Mountain Lake. The area offers sensational outdoor activities but also a surprising array of cultural activities from fine dining, to multiple musical venues and playhouses, to symphonies and ballets. Access to major air-travel hubs is remarkably easy through the Roanoke Airport. The weather features mild winters, an abundance of sun, and extended springs and autumns. The region features top-notch schools and Universities and has been coined “the best kept secret in the east.”

Please contact: Amy Silcox, Physician Recruiter amsilcox@carilonclinic.org 540-224-5187 Equal Opportunity Employer: Minorities/Females/Protected Veterans/ Individuals with Disabilities/Sexual Orientation/Gender Identity

physician neeDeD northern virginia area I am looking for a physician to join our team at the Kaplan Center for Integrative Medicine located in McLean, Virginia (www.kaplanclinic.com).

This is a wonderful opportunity for someone to join a unique and established integrative medicine practice.

Our practice specializes in the treatment of chronic pain and illness and has delivered a broad range of cutting-edge conventional and alternative medicine health care for over 25 years. A teaching affiliate of Georgetown University Medical School, the Kaplan Center has an outstanding reputation to go along with its being the oldest integrative medical clinic in the Washington, D.C. area.

The ideal physician will have a background in family medicine; musculoskeletal pain management including skills in U/S guided injections and prolotherapy/ regenerative medicine. Additionally, candidates should possess the ability to connect with patients on a personal level. Training in manual medical skills would be a significant plus. Features include: • A medical team comprised of physicians, physical therapists, a psychotherapist, nurses and a dietitian.

• Bi-weekly provider meetings to coordinate patient care and to share treatment insights and recommendations.

• Comprehensive treatment approach that may incorporate: omt; prolotherapy; prp; medical acupuncture; bioidentical hormone therapy; psychotherapy; physical therapy; craniosacral therapy; lymph Drainage; nutritional counseling.

• Outpatient, fee-for-service practice, with patient sessions that last from 30 to 60 minutes.

• Generous compensation and benefits package (including health insurance, retirement savings plan, liability insurance, license fees and CME allowance). mclean is located a few miles west of our nation’s capital in the heart of northwest fairfax county. This friendly community of over 60,000 offers beautiful tree-lined residential areas, a bustling downtown, upscale restaurants, Fortune 500 companies, prestigious schools, scenic parks and trails, an abundance of recreational activities and cultural attractions.

If you are interested in this opportunity, please contact our Executive Director, John Doleman, at 703-532-4892 x 651. If email is preferable, please use j.doleman@kaplanclinic.com.

Our mission at Aeon Clinical is better patient care through state of the art Toxicology, personalized Pharmacogenomics and Cancer Genomic testing.

We are confident that partnering with us will provide you with the most accurate analysis and timely results to optimize your treatment plan.

Use Aeon Clinical for your testing needs so you can Prescribe with Confidence.

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Do yoU ache for a new opportUnity?

Aurora Health Care, the largest health care system in Wisconsin, currently has opportunities for pain medicine physicians in the following locations: oshKosh: We are seeking a Director for our comprehensive pain management program. You will see patients, do procedures and manage the day-to-day operations of the program.

Kenosha: As part of an interdisciplinary team you will be responsible for treating patients and managing their medication needs. milwaUKee: This unique program ensures patients are provided with the best treatment options available. You will manage pain medications and do procedures as necessary.

Physicians must be trained in an accredited residency program and have fellowship training in pain medicine. We offer a competitive salary and a comprehensive benefits package that includes paid medical liability insurance and relocation assistance.

Aurora Health Care is the largest health care system in Wisconsin. With service areas extending to Northeastern Illinois, Aurora is anchored by two top tier tertiary/quaternary care centers. Our integrated delivery model allows Aurora physicians and advanced practice professionals to support their patients, connect with colleagues and offer state-of-the-art, top tier quality care For more information, please contact Alison Burki at 800-307-7497 ext. 13, or email alison.burki@aurora.org. You can also browse our website at aurora.org/doctor.

THE PA IN PRACTITIONE R

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