Applying Quality to Postsurgical Opioid-Induced Constipation

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1 Applying Quality to Postsurgical Opioid-Induced Constipation Applying Quality to Postsurgical Opioid-Induced Constipation Ernest J. Dole, PharmD, PhC, FASHP, BCPS Clinical Pharmacist University of New Mexico Hospitals Pain Consultation & Treatment Clinic Clinical Associate Professor University of New Mexico College of Pharmacy Albuquerque, New Mexico Faculty and Staff Disclosures Ernest J. Dole, PharmD, PhC, FASHP, BCPS, has no relevant financial relationships with commercial interests to disclose. Pharmacy Times Continuing Education Planning Staff: Dave Heckard; Maryjo Dixon, RPh; Dipti Desai, PharmD, RPh; Jyoti Arya, PharmD, RPh; Susan Pordon; and Donna Fausak have no financial relationships with commercial interests to disclose. An anonymous peer reviewer has been used as part of content validation and conflict resolution. The peer reviewer has no relevant financial relationships with commercial interests to disclose. The content of this symposium may include information regarding the use of products that may be inconsistent with, or outside the approved labeling for, these products in the United States. Pharmacists should note that the use of these products outside current approved labeling is considered experimental and are advised to consult the prescribing information for these products. Learning Objectives At the completion of this activity, participants will be able to: Demonstrate an understanding of the prevalence and severity of OIC caused by postsurgical opioid prescribing Examine current and emerging pharmacologic treatments that can be used to prevent and treat OIC Determine quality metrics that should be monitored to ensure that patients receive safe and effective opioid treatment Identify the role of pharmacists in the prevention and treatment of OIC Use of Opioids in Chronic Pain: Balancing Act Pain as the 5th vital sign Starting in 2001, the Joint Commission officially recognized that pain is a major health problem and that patients have the right to appropriate assessment and management of pain A Balancing Act: Public Health A crisis of abuse of prescription opioid medication The US opioid epidemic is continuing, and drug overdose deaths nearly tripled during Among 47,055 drug overdose deaths that occurred in 2014 in the United States, 28,647 (60.9%) involved an opioid Veterans Health Administration. Pain as the 5th vital sign toolkit. October 2000, revised edition. Geriatrics and Extended Care Strategic Healthcare Group, National Pain Management Coordinating Committee. Accessed August 17, Rudd RA, et al. Increases in Drug and Opioid-Involved Overdose Deaths United States, MMWR Morb Mortal Wkly Rep. 2016;65: doi: 1

2 National Institute on Drug Abuse. Accessed August 1, National Institute on Drug Abuse. Accessed August 1, A Balancing Act: Patient s Expectations Of being pain free Of magic bullet medications Of presence of undesirable and unexpected adverse effects of opioids (ie, constipation) Of unlimited supply of medications opioids while being prescribed chronic opioid therapy (COT) for chronic noncancer pain (CNCP) of not having to do any work Of physical therapy Of behavioral health Of no consequences for their decisions Of being honest A Balancing Act: Providers Realities The incidence of alcoholism and addiction in the general population is 5%-10% One addict affects 7-10 people The prevalence of current or past substance use disorders in patients receiving chronic opioids for CNCP may be ~ 40% or higher The principles of chronic medication management are often forgotten when managing opiate medication Clash of providers and patients values Fishbain DA, et al. Pain Med. 2008;9: Prevalence of Opioid-Induced Constipation (OIC) in Opioid Management Prescribing rates of opioids are approximately 37%-50% in postoperative surgery setting OIC is the most common gastrointestinal adverse effect impacting patients who take opioids A meta-analysis reveals that the prevalence of OIC in noncancer patients receiving opioids is 41%; however, this rate varies from 14% to 90% in individual studies The likelihood of OIC increases as the duration of opioid use increases, and patients may discontinue opioid therapy upon the development of constipation Classification and Identification of OIC The Rome III criteria definition of constipation is generally used to identify OIC although there is no consistent definition. Consensus definition has been developed to standardize future clinical trials: o Change from baseline in bowel habits and change in defecation patterns after the initiation of opioid therapy o Patterns are characterized by the occurrence of the following: decreased frequency of spontaneous bowel movements (BMs), worsening of straining to pass BMs, sense of incomplete evacuation, or harder stool consistency Kalso E, et al. Pain. 2004;112: ; Gudin J, et al. Combatting opioid-induced constipation: new and emerging therapies. Practical Pain Management website. constipation-new-emerging-therapies. Updated April 14, Gaertner J, et al. J ClinGastroenterol. 2015;49:

3 Complications of Untreated/Mismanaged OIC Patients may be at increased risk for bowel dysfunction, fecal impaction, incontinence, and inadequate drug absorption Studies illustrate that work productivity and activity impairment decreases due to this condition, equating to approximately 14 hours of lost productivity per week Patients are more likely to alter their dosing regimen due to this adverse effect; 28% of patients use lower doses; 33% of patients will skip, decrease, or eliminate doses to ease constipation Ripple out effect of these decisions on therapy Impact of OIC Prospective, longitudinal, observational cohort study conducted in the United States, Canada, Germany, and the United Kingdom in patients aged years (N = 489), who had been receiving daily opioid therapy for 4 weeks for chronic noncancer pain with presence of OIC in the past 2 weeks: Importance and severity of OIC are perceived differently by patients and their providers This discordance complicates pain management and illustrates a need for improved communication OIC symptoms, laxative use and effectiveness, and impact of OIC on pain management and quality of life were not fully appreciated by the patient s providers These disparate perceptions indicate a need for clinical education and an opportunity for pharmacists to provide education regarding OIC to patients and their providers Coyne KS, et al. Clinicoecon Outcomes Res. 2014;6: ; Bell TJ, et al. Pain Med. 2009;10(1): LoCasale RJ, et al. J Manag Care Spec Pharm. 2016;22: Impact of OIC Survey of 513 patients on COT with OIC from United States, Canada, United Kingdom, Germany, Sweden, and Norway Produced 289 text responses on what straining meant on quality of life (QOL); 469 text responses on what relief of symptoms of OIC would mean to them OIC secondary to COT for CNCP affects the way patients live their lives in the 3 domains of physical, psychological, and practical implications Lubiprostone Approved by the FDA in 2013 for the treatment of OIC in adult patients with chronic noncancer pain Selective type 2 chloride channel activator (CIC-2) leading to increases in intestinal fluid secretion, leading to increased gut motility Dosing: 24 mcg twice daily and should be administered with food. ADRs: nausea, diarrhea, headache, abdominal pain and distension, and flatulence Epstein RS, et al. Adv Ther. 2017;34: Gudin J, et al. Combating opioid-induced constipation: new and emerging therapies. Practical Pain Management website. Updated April 14, Accessed August 18,2017; Marciniak CM, et al. World J Gastroenterol. 2014;20(43): Oxycodone/Naloxone Naloxone, administered orally, acts locally on mu opioid receptors in the GI tract Oxycodone and naloxone administered in a ratio of 2:1 has been shown to relieve constipation and is associated with few adverse effects. It has also been associated with improvements in quality of life ADRs: nausea, vomiting, headache, constipation, and diarrhea Tapentadol mu-opioid agonist that also inhibits the reuptake of norepinephrine, contributing to its analgesic effect In a study involving 343 patients with cancer, the incidence of gastrointestinal treatmentassociated adverse events was lower in the tapentadol group (55.4% [93/168]) than in the oxycodone group (67.4% [116/172]) ADRs: nausea, vomiting, dizziness, drowsiness, fatigue, headache Nelson D, et al. Ther Adv Chronic Dis. 2016;2: Nelson D, Camilleri M. Ther Adv Chronic Dis. 2016;7:

4 Mu-opioid receptor antagonists Designed to inhibit the peripheral effects of opioid medications in the GI tract without reducing analgesia or inducing opiate withdrawal Act locally to inhibit opioid binding in the GI tract Methylnaltrexone: should be used with caution in patients with gastrointestinal perforation, severe and persistent diarrhea, and disruptions in the blood brain barrier ADRs: abdominal pain, flatulence, nausea, vomiting, dizziness, diarrhea, and hyperhidrosis Mu-Opioid Receptor Antagonists Naloxegol Does not cross blood brain barrier; potential for drug-drug interactions with centrally acting opioids is limited Is a CYP3A4 and P-gp substrate; the dose of naloxegol should be reduced by 50% when prescribed with CYP3A4 inhibitors Contraindicated in patients at risk or with GI obstruction due to an increased risk for perforation ADRs: abdominal pain, diarrhea, nausea, headache, and flatulence Nelson D, et al. Ther Adv Chronic Dis. 2016;7: Nelson D, Camilleri M. Ther Adv Chronic Dis. 2016;7: Mu-Opioid Receptor Antagonists Naldemedine Evaluated in the COMPOSE clinical trial program, which examined the effectiveness and safety of naldemedine with placebo in patients with OIC and chronic, noncancer pain Naldemedine was associated with a statistically significant improvement in the frequency of BMs per week compared with placebo; after 52 weeks, revealed long-term safety with no statistically significant signs or symptoms of opioid withdrawal ADRs: similar to other agents in group Emerging Treatments Linaclotide: guanylate cyclase C agonist that increases fluid secretion, increasing section of chloride and bicarbonate into the intestinal lumen Prucalopride: 5-HT4 agonist that causes the release of 5-hydroxytryptamine from the enterochromaffin cells of the GI tract, causing the release of acetylcholine and calcitonin gene-related peptide, leading to relaxation of the GI tract Axelopran: mu-receptor antagonist being developed for the treatment of OIC Naldemedine Phase III Study Demonstrates Long-Term Safety And Efficacy For The Treatment Of Opioid-Induced Constipation. Accessed May 8, Sloots C, et al. Dig Dis Sci. 2010;55: ; Vickery R, et al. Pain. 2013;6:1111. Quality Indicators in Pain and OIC Management With the increase in prescribing of opioid medication for COT in CNCP, health plans and accrediting agencies such as JCAH needed an objective method to assess performance of providers and hospitals and the treatment of adverse effects of opioid medication. Quality Indicators in Pain and OIC Management Patient-Reported Outcome Assessment Tools Bowel Function Index (BFI): questionnaire that assesses ease of defecation, feeling of incomplete evacuation, and patient s personal judgment of constipation BFI score change of at least 12 points is considered a clinically significant change in constipation Endorsed by the following guideline: Müller-Lissner S, Bassotti G, Coffin B, et al. Opioid-induced constipation and bowel dysfunction: a clinical guideline. Pain Med. Dec 15, pii: pnw255. doi: /pm/pnw255 4

5 Quality Indicators in Pain and OIC Management Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) This rating system measures patients perspectives on hospital care in 8 domains such as doctor communication, care transition, discharge information, and pain management Health systems should ensure they have processes and resources (eg, staff, equipment, facilities) in place to regularly assess, monitor, and follow up on pain diagnoses according to Joint Commission Standard Quality Indicators in Pain and OIC Management Bristol Stool Chart allows patients to identify their form using different images and written description of stool types: Bowel function diary: validated to characterize and quantify constipation symptoms related to opioid use per FDA guidance; supports the validity of composite patient-reported outcomes, endpoints, and symptom severity items that are relevant to patients Medicare.gov. Survey of patients experiences (HCAHPS) star ratings. Available from: Access May 8, 2017; The Joint Commission. Pain Management. Accessed May 8, The Joint Commission. Pain Management. Accessed May 8, 2017; Amarenco G. Prog Urol. 2014;24(11): Best Practice Guidelines for OIC Müller-Lissner S, Bassotti G, Coffin B, et al. Opioid-Induced constipation and bowel dysfunction: a clinical guideline. Pain Med. Dec 15, pii: pnw255. doi: /pm/pnw255 Drewes AM, Munkholm P, Simrén M, et al. Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction: recommendations of the Nordic Working Group. Scand J Pain. 2016;11: doi: /j.sjpain Poulsen JL, Brock C, Olesen AE. Evolving paradigms in the treatment of opioid-induced bowel dysfunction. Therap Adv Gastroenterol. 2015;8: doi: / X Nelson AD, Camilleri M. Opioid-induced constipation: advances and clinical guidance. Ther Adv Chronic Dis. 2016;7(2): doi: / Pharmacists Role in OIC Prevention and Treatment Identify the signs and symptoms of OIC and recognize when uncontrolled pain may be due to medication nonadherence Provide clinical recommendations about appropriate treatment when OTC agents are ineffective Assist with formulary management decisions Assist with improving the rating of the HCAHPS surrounding pain management Pharmacists Role in OIC Always remember that OIC can occur as long as your patient is taking opioid medication. Therefore, a bowel regimen should always be present for the duration of opioid therapy. This is often forgotten. Ask your patients directly if they are having problems with constipation. Use any laxative or medication designed to combat constipation carefully in the setting of IBD, or if the patient has an acute change in bowel habits. Pharmacists Role in OIC Be familiar with your patient s health plan criteria for use with these newer OIC agents Be aware that mu-opioid antagonists have a small chance of including opioid withdrawal Be familiar with the fact that one-third of patients on chronic opioid therapy alter their opioid therapy secondary to OIC, possibly contributing to a perceived lack of efficacy of the opioid therapy at the current dose, possibly leading to an increase in opioid dose, leading to more OIC..and so on 5

6 Conclusion Additional Resources Opioid prescribing has increased; as such, OIC has increased OIC is the most common GI opioid ADR, which can lead to non-adherence There are multiple agents available to treat OIC when laxatives do not work Pharmacists are in an ideal position to assess patients for non-adherence, monitor for drug-drug interactions, monitor for appropriate dosing of agents, monitor for ADRs, provide medication recommendations, formulary recommendations, and most costeffective therapy For patients: arch&uadpub=bing&ucampaign=unbranded%20general&ucreative=oic%20condition&u place=opioid%20induced%20constipation For healthcare professionals: 1. Veterans Health Administration. Pain as the 5th vital sign toolkit. October 2000, revised edition. Geriatrics and Extended Care Strategic Healthcare Group, National Pain Management Coordinating Committee. Accessed August 17, Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths United States, MMWR Morb Mortal Wkly Rep. 2016;65: doi: 3. Fishbain DA, Cole B, Lewis J, Rosomoff HL, Rosomoff RS. What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and/or aberrant drug-related behaviors? A structured evidence-based review. Pain Med. 2008;9: Kalso E, Edwards JE, Moore RA, et al. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain. 2004;112: Gudin J, Fudin J, Laitman A, Kominek C. Combating opioid-induced constipation: new and emerging therapies. Practical Pain Management website. constipation-new-emerging-therapies. Accessed September 5, Gaertner J, Siemens W, Camilleri M, et al. Definitions and outcome measures of clinical trials regarding opioid-induced constipation: a systematic review. J Clin Gastroenterol. 2015;49: Coyne KS, LoCasale RJ, Datto CJ, Sexton CC, Yeomans K, Tack J. Opioid-induced constipation in patients with chronic non-cancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review. Clinicoecon Outcomes Res. 2014;6: Bell TJ, Panchal SJ, Miaskowski C, et al. The prevalence, severity, and impact of opioidinduced bowel dysfunction: results of a US and European patient survey (PROBE 1). Pain Med. 2009;10(1): Marciniak CM, Toledo S, Lee J, et al. Lubiprostone vs. Senna in postoperative orthopedic surgery patients with opioid-induced constipation: a double-blind, active-comparator trial. World J Gastroenterol. 2014;20(43): Nelson AD, Camilleri M. Opioid-induced constipation: advances and clinical guidance. Ther Adv Chronic Dis. 2016;2: Naldemedine phase III study demonstrates long-term safety and efficacy for the treatment of opioid-induced constipation. Accessed May 8, Sloots CE, Rykx A, Cools M, Kerstens R, De Pauw M. Efficacy and safety of prucalopride in patients with chronic noncancer pain suffering from opioid-induced constipation. Dig Dis Sci. 2010;55: Vickery R, Lebster L, Li Y, Schwertschlag U, Singla N, Canafax D. TD-1211 Phase 2b study demonstrates increased bowel movement frequency in patients with opioid-induced constipation regardless of baseline opioid dose. Pain. 2013;6: The Joint Commission. Pain Management. Accessed May 8, Amarenco G. Bristol Stool Chart: Prospective and monocentric study of stools introspection in healthy subjects. Prog Urol. 2014;24(11): Medicare.gov. Survey of patients experiences (HCAHPS) star ratings. Accessed May 8,