Opioid-Induced Constipation: Proactive Diagnosis and Targeted Management

April 30, 2015 Grand Ballroom AB The Westin Boston Waterfront Boston, Massachusetts This activity is jointly provided by Global Education Group and Integritas Communications.

This activity is supported by an educational grant from AstraZeneca.

This event is not a part of the official Internal Medicine Meeting 2015 Education Program.

CME/MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

FACULTY FACULTY

Anthony J. Lembo, MD Prerecorded Associate Professor of Medicine Director, GI Motility Laboratory Harvard Medical School Beth Israel Deaconess Medical Center Boston, Massachusetts

Brooks Cash, MD Professor of Medicine University of South Alabama Health System Digestive Health Center Mobile, Alabama

Charles E. Argoff, MD Professor of Neurology Albany Medical College Director, Comprehensive Pain Center Albany Medical Center Albany, New York

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PREAMBLE

STATEMENT OF NEED/PROGRAM OVERVIEW As many as 100 million adults in the United States suffer from chronic pain.1 Among the multitude of available treatment modalities, opioids are the cornerstone for cancer pain treatment and palliative care, and they have gained increasing acceptance as an important therapeutic option for carefully selected patients with chronic noncancer pain.2,3 Yet, opioid side effects often create significant barriers to good patient outcomes.4,5 Constipation is the most common opioid-related adverse effect, affecting up to 50% of patients on long-term therapy.6-10 Opioid-induced constipation is especially burdensome because—unlike many other adverse effects of opioids—patients do not develop tolerance to treatment-related reductions in bowel motility and increases in gastrointestinal fluid absorption.5 Clinicians must proactively consider and appropriately manage opioid-related side effects—most notably, constipation. By pre-emptively explaining the risk for opioid-induced constipation, clinicians can prepare patients to discuss changes in their bowel habits and adopt prophylactic or additional management strategies that can ease this burdensome side effect. During this Interactive Exchange™ program, expert faculty will provide practical insights into structured evaluations of bowel habits, prophylactic bowel regimens, and newer pharmacologic approaches that antagonize opioid receptor activation in the gastrointestinal tract, thereby targeting the underlying cause of opioid-induced constipation.

REFERENCES 1. Institute of Medicine. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. 2011. http://www.iom.edu/Reports/2011/Relieving-Painin-America-A-Blueprint-for-Transforming-Prevention-Care-Education-Research.aspx.

Accessed March 2015.

2. Chou R, Fanciullo GJ, Fine PG, et al. J Pain. 2009;10(2):113-130.

3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain. 2010;2010. http://www.nccn.org/professionals/physician_gls/f_ guidelines.asp. Accessed March 2015.

4. Daniell HW. Am J Med. 2007;120(9):e21.

5. McNicol E, Horowicz-Mehler N, Fisk RA, et al. J Pain. 2003;4(5):231-256.

6. Bell TJ, Panchal SJ, Miaskowski C, et al. Pain Med. 2009;10(1):35-42.

7. Cook SF, Lanza L, Zhou X, et al. Aliment Pharmacol Ther. 2008;27(12):1224-1232.

8. Panchal SJ, Muller-Schwefe P, Wurzelmann JI. Int J Clin Pract. 2007;61(7):1181-1187.

9. Villars P, Dodd M, West C, et al. J Pain Symptom Manage. 2007;33(1):67-77.

10. Benyamin R, Trescot AM, Datta S, et al. Pain Physician. 2008;11(suppl 2):S105-S120.

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TARGET AUDIENCE The educational design of this activity addresses the needs of pain specialists and other health care providers involved in the treatment of patients with opioid-induced constipation.

EDUCATIONAL OBJECTIVES After completing this activity, the participant should be better able to: • Evaluate baseline bowel habits, risk factors for OIC development, and ongoing changes in bowel function in patients on long-term opioid therapy

PREAMBLE

• Implement a prophylactic treatment plan to address OIC concurrent with the initiation of opioid therapy • Analyze current pharmacotherapies for OIC based on mechanisms of action and data on efficacy and safety • Tailor treatment regimens for patients experiencing OIC according to symptom severity, past treatment responses, and patient preferences • Discuss the essential elements of opioid pharmacology with specific focus on the effects of opioid receptor activation in the gastrointestinal tract • Communicate with opioid-treated patients about treatment-emergent adverse events through open, patient-centered dialogue throughout the course of therapy

PROGRAM AGENDA 6:30 pm – 7:00 pm Registration, Meal, Preactivity Assessment 7:00 pm – 7:10 pm Disease Management Primer 7:10 pm – 7:55 pm Case Series in Opioid-Induced Constipation 7:55 pm – 8:15 pm Choose-a-Case 8:15 pm – 8:30 pm Postactivity Assessment and Question and Answer Session

PHYSICIAN ACCREDITATION STATEMENT This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group (Global) and Integritas Communications. Global is accredited by the ACCME to provide continuing medical education for physicians.

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PHYSICIAN CREDIT DESIGNATION Global Education Group designates this live activity for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

GLOBAL CONTACT INFORMATION

PREAMBLE

For information about the accreditation of this program, please contact Global at 303-395-1782 or inquire@globaleducationgroup.com.

INSTRUCTIONS TO RECEIVE CREDIT In order to receive credit for this activity, the participant must complete the evaluation form and return to a staff member at the conclusion of the program.

FEE INFORMATION & REFUND/CANCELLATION POLICY There is no fee for this educational activity.

DISCLOSURE OF UNLABELED USE This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. Global Education Group (Global) and Integritas Communications do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

DISCLOSURE OF CONFLICTS OF INTEREST Global Education Group (Global) requires instructors, planners, managers, and other individuals and their spouses/life partners who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

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The faculty reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity:

Brooks Cash, MD

Speakers Bureau for AstraZeneca plc, Salix Pharmaceuticals, Inc., and Takeda Pharmaceutical Company Limited.

Charles E. Argoff, MD

PREAMBLE

Speakers Bureau for Allergan, Inc., AstraZeneca plc, Depomed Inc., Iroko Pharmaceuticals LLC, Janssen Pharmaceuticals, Inc., Millenium Laboratories, and Xenoport Inc. Grant/ Research Support from Endo Pharmaceuticals Inc., Forest Laboratories, and Eli Lilly and Company. Consultant/Independent Contractor to AstraZeneca plc, Depomed Inc., Endo Pharmaceuticals, Nektar Therapeutics, Pfizer, Inc., Xenoport Inc., and Zogenix, Inc. Stock Shareholder of Depomed Inc. and Pfizer Inc. Royalties from Elsevier B.V.

Anthony J. Lembo, MD

Consultant/Independent contractor to AstraZeneca plc, Ironwood Pharmaceuticals, Inc., Prometheus Laboratories Inc., and Salix Pharmaceuticals, Inc. Grant/Research Support from Prometheus Laboratories Inc. The planners and managers reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity:

Ashley Marostica, RN, MSN Amanda Glazar, PhD Andrea Funk Rose O’Connor, PhD

Nothing to disclose Nothing to disclose Nothing to disclose Nothing to disclose

DISCLAIMER Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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Bristol Stool Form Scale Bristol Stool Description

Form Scale

Image

Bristol Stool Description

Form Scale

Image

Bristol Stool Form Scale

Bristol Stool Form Scale CLINICAL ASSESSMENT TOOLS Description

Description Separate hard lumps, like nuts

Bristol Stool Form Scale

Description Separate hard lumps, like nuts

Bristol StoolStool Form Scale Bristol Form Scale Description

Separate hard hard lumps, lumps, like like nuts nuts Separate

Description Separate hard lumps, like nuts Sausage-shaped but lumpy

Type

Description

Image

Image

Image Image Image

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Separate hard lumps, like nuts Sausage-shaped but lumpy Sausage-shaped Separate Separate hard lumps, like nuts 1but lumpy

Sausage-shaped but lumpy

hard lumps, like nuts

Sausage-shaped lumpy Like a sausage or but snake but with cracks on its surface Sausage-shaped lumpy Like a sausage 2 orbut snake but with cracks on Sausage-shaped but its lumpy Like a sausage or snake but with cracks on its surface surface Sausage-shaped lumpy Like a sausage orbut snake but with cracks on its surface sausage oron snake Like a sausage or snake Like but awith cracks its but 3 surface with cracks its surface Like a sausage or snake, smooth andon soft Like a sausage or snake but with cracks on its Like a sausage or snake, smooth and soft surface Like a sausage or snake, smooth and soft Like a sausage or snake but with cracks on its Like a sausage or snake, surface Like a sausage 4 or snake, smooth and soft

smooth and soft

Like a sausage or snake, smooth and soft

Soft blobs blobs with with clear-cut clear-cut edges edges Soft

Like a sausage or snake, smooth and soft Soft blobs with 5 clear-cut edges Soft blobs with clear-cut edges

Fluffy pieces with ragged edges edges, a mushy stool Soft blobs with clear-cut

Fluffy pieces with ragged edges, a mushy stool

Fluffy pieces with 6 ragged edges, a mushy stool

Soft blobs with clear-cut edges Fluffy pieces with ragged edges, a mushy stool Soft blobs with clear-cut edges Fluffy pieces with ragged edges, a mushy stool

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withWatery, permission Lewis SJ, Heaton KW, Scandinavian Journal of Gastroenterology, 1997; 32(9):920–924. nofrom solid pieces »» http://bowelcontrol.nih.gov/Bristol_Stool_Form_Scale_508.pdf Healthcare.

Heaton KW. ScandaJ Gastroenterol.

1997;32(9):920–924.

Fluffy piecesLewis withSJ,ragged edges, mushy stool

nofrom solid pieces withWatery, permission Lewis SJ, Heaton KW, Scandinavian Journal of Gastroenterology, 1997; 32(9):920–924.

Healthcare.

nofrom solid pieces d withWatery, permission Lewis SJ, CME Heaton KW, Scandinavian Journal of Gastroenterology, 1997; 32(9):920–924.

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RESOURCE CENTER

Like a sausage or snake, smooth and soft Soft blobs with clear-cut edges

NOTES

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CLINICAL ASSESSMENT TOOLS Bowel Function Index Please answer the following three questions by making a mark on the line between 0 and 100. Please transfer the results to the open squares at the bottom of the page. Add the three results and divide by three.

Question 1 (Q1) How would you rate the ease of defecation during the last 7 days according to patient assessment?

0=Easy/no difficulty

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100=Severe difficulty

Question 2 (Q2) Does your patient feel that his/her bowel evacuation has been incomplete during the last 7 days?

0=Not at all

50

100=Very strongly

Question 3 (Q3) How would you judge your patient’s constipation throughout the last 7 days?

50

100=Very heavily constipated

RESOURCE CENTER

0=No constipation at all

Results Q1

Q2

+

Q3

+

Sum

=

Total

/3=

Adapted from Rentz AM, et al. J Med Econ. 2009;12(0):371-383.

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CLINICAL ASSESSMENT TOOLS »» Patient Assessment of Constipation (PAC-SYM) This 12-item questionnaire of patient-reported symptoms assesses 3 subscales of symptoms (bowel movements, rectal symptoms, and abdominal symptoms) over the prior 2 weeks. www.proqolid.org/content/download/11747/176511/version/2/ file/PAC-SYM12_2.1_eng-US_review+copy.pdf

PATIENT RESOURCES »» Patient Conversation Guide This patient tool can be completed prior to the visit with the health care provider to guide a meaningful conversation about bowel habits and constipation symptoms. www.theacpa.org/uploads/ACPA-Opioid_Constipation_Chart-V4.pdf

»» Patient Education Handout This leaflet provides patients with approaches to mitigate opioidinduced constipation and includes a list of questions about constipation for patients to ask their doctors or clinics. www.acponline.org/patients_families/products/health_tips/oic_en.pdf

PRACTICE GUIDELINES »» The Functional Gastrointestinal Disorders and the Rome III Process, 2006.

Drossman DA. Gastroenterology. 2006;130(5):1377-1390. www.ncbi.nlm.nih.gov/pubmed/16678553

RESOURCE CENTER

»» Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain, 2009.

Chou R, et al. J Pain. 2009;10(2):113-130. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043401/

»» VA/DoD Clinical Practice Guideline: Management of Opioid Therapy for Chronic Pain, 2010.

Department of Veterans Affairs, Department of Defense. www.healthquality.va.gov/guidelines/Pain/cot/COT_312_Full-er.pdf

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OTHER RESOURCES »» A Clinical Guide to Opioid Analgesia. 2nd edition.

Fine PG, Portenoy RK. New York, NY: Vendome Group, LLC; 2007. www.amazon.com/A-Clinical-Guide-Opioid-Analgesia/dp/1933692626#

»» Responsible Opioid Prescribing: A Clinician’s Guide. 2nd edition, revised and expanded.

Fishman SM. Washington, DC: Waterford Life Sciences; 2012. library.fsmb.org/cme/index.html

SUGGESTED READING »» Opioid-induced bowel dysfunction: epidemiology, pathophysiology, diagnosis, and initial therapeutic approach.

Dorn S, et al. Am J Gastroenterol. 2014;2(1):31-37.

»» Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review.

Coyne KS, et al. Clinicoecon Outcomes Res. 2014;6:269-281.

»» Constipation in people prescribed opioids.

Ahmedzai SH, Boland J. BMJ Clin Evid (Online). 2010;pii:2407.

»» The narcotic bowel syndrome: a recent update.

Drossman D, Szigethy E. Am J Gastroenterol. 2014;2(1):22-30.

RESOURCE CENTER

»» Opioids in chronic non-cancer pain: systematic review of efficacy and safety.

Kalso E, et al. Pain. 2004;112(3):372-380.

»» A multi-institutional study analyzing effect of prophylactic medication for prevention of opioid-induced gastrointestinal dysfunction.

Ishihara M, et al. Clin J Pain. 2012;28(5):373-381.

»» A volunteer model for the comparison of laxatives in opioid-related constipation.

Sykes NP. J Pain Symptom Manage. 1996;11(6):363-369.

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»» Establishing “best practices” for opioid rotation: conclusions of an expert panel.

Fine PG, et al. J Pain Symptom Manage. 2009;38(3):418-425.

»» Naloxegol for opioid-induced constipation in patients with noncancer pain.

Chey WD, et al. N Engl J Med. 2014;370(25):2387-2396.

»» A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain.

Cryer B, et al. Pain Med. 2014; 15(11):1825-1834.

»» Clinical evaluation of the efficacy of methylnaltrexone in resolving constipation induced by different opioid subtypes combined with laboratory analysis of immunomodulatory and antiangiogenic effects of methylnaltrexone.

Neefjes ECW, et al. BMC Palliative Care. 2014;13:42.

»» Patient preference with respect to QoL and reduction in opioid-induced constipation after treatment with prolonged-release oxycodone/naloxone compared with previous analgesic therapy [PREFER study].

RESOURCE CENTER

van Dongen VCPC, et al. Int J Clin Pract. 2014;68(11):1364-1375.

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