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Drug List Learning Objectives Opioids 10:30 – 11:45 am Presenter Disclosure Information Personalized Approach to OIC: The following relationships exist related to this presentation: Improving Communication and ►Jeffrey A. Gudin, MD: Speakers Bureau for AstraZeneca and Managing Treatment Salix Pharmaceuticals, Inc. Advisory Board for Daiichi Sankyo, Inc. SPEAKER Off-Label/Investigational Discussion Jeffrey A. Gudin, MD ►In accordance with pmiCME policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Drug List Learning Objectives • Axelopran: Investigational • • Bisacodyl: Dulcolax®, Bisac‐EvacTM, Correctol® Outline prevalence, severity, and resulting • Docusate sodium: Aqualax®, Colace®, Colace® Micro‐Enema burden of OIC on patients • Husk: Fybogel®, Ispagel® • IR Tapentadol: Nucynta® • Compare and contrast the best OIC treatment • Lactulose: KristaloseTM, Constulose • Lubiprostone: Amitiza® options for patient‐specific situations • Methylnaltrexone: Relistor® • • Methylcellulose: Citrucel® Demonstrate specific and targeted questions • Naloxegol: MovantikTM for patients that can improve patient‐clinician • Naldemedine: Investigational • Polyethylene Glycol: MiraLAX® communication about OIC • Prucalopride: Resolor® • PR Oxycodone/Naloxone: Targin®, TarginiqTM, Targinact® • SP‐333: Investigational IR=immediate release Prevalence Opioids Treatment Burden Algorithm • Considered “broad spectrum” analgesics effective for multiple nociceptive and neuropathic pain types • Approximately 250 million Rx written annually for opioids in US Safety and HCEO $$$ Warnings OIC • Controversy exists surrounding total daily dosing recommendations • Many potential side effects – Somnolence, nausea, itching, respiratory depression Rx Patho‐ • Constipation most common and most bothersome Therapies physiology OTC – Affects quality of life and function Treatment OIC=opioid‐induced constipation; Rx=prescription; OTC=over‐the‐counter; HCEO=health care economic outcomes Coyne KS, et al. Clinicoecon Outcomes Res. 2014;6:269‐281. Development of Constipation As a Result…OIC Is Increasing Risk Factors • With the increase in opioid use, more patients are It is important to note, not all constipation while on opioids is OIC presenting with opioid‐induced constipation (OIC)1 • Among patients taking opioids, 40‐90% have constipation and other gastrointestinal side effects which can Patient Dietary Drug Regimen Medical Issues adversely affect adherence to pain medication regimens Characteristics Considerations • Opioids • Relative immobility and quality of life2‐6 • Female gender • Dehydration • Anticholinergics • Nausea/vomiting • Advanced age • Nutritional deficits • Magnesium • Mechanical obstruction • Unlike other opioid‐related side effects, OIC is not dose‐ • Calcium • Recent hospitalizations 4 • Antidepressants dependent nor does is resolve over time • Antihistamines • Instead, OIC remains a significant burden on patients and the health care system4 1Nevins PH, et al. Pain Week. 2013. 2Chey W, et al. N Engl J Med. 2014;370(25):2387‐2396. 3Holzer P. Therapy. 2008;5:531‐543. 4Bell TJ, et al. Pain Med. 2009;10:35‐42. 5Kalso E, et al. Pain. 2004;112:372‐380. 6Tuteja AK, et al. Kalso E, et al. Pain. 2004;112(3):372‐380.; Ahmedzai SH, Boland J. Clin Evid (Online). 2010;pii:2407.; Clemens KE, Neurogastroenterol Motil. 2010;22:424‐430, e96. Klaschik EK. Ther Clin Risk Manag. 2010;6:77‐82.; Wan Y CS, et al. Las Vegas, Nevada; 2013; Abstract 132. Physiological Effects of Opioid‐Agonists in the GI Tract: More than “Constipation” Proposed Definitions of OIC • Delay gut transit time Proposed Definitions of OIC Camilleri, et al. (2014)1 Gaertner, et al. (2015)2 • Results in excessive water resorption Consensus statement: A A change, when initiating opioid therapy, • Stimulate mucosal sensory receptors change when initiating opioid from baseline bowel habits, defecation therapy from baseline bowel patterns, and what individuals would – May result in pain habits that is characterized by consider as abnormal that is characterized • Stimulate non‐propulsive motility any of the following1: by any of the following2: 1. Reduced BM frequency 1. Reduced frequency of SBMs (in • Reduce GI secretions contrast to induced BMs) • Tightens/constricts pylorus and ileocecal sphincters 2. Development or worsening of straining to pass BMs 3. A sense of incomplete rectal evacuation 4. Harder stool consistency BM=bowel movement; SBM=spontaneous bowel movement GI=gastrointestinal 1Camilleri M, et al. Neurogastroenterol Motil. 2014;26(10):1386‐1395. 2Gaertner J, et al. J Clin Gastroenterol. Camilleri M, et al. Am J Gastroenterol. 2011;106(3):497‐506.; Panchal SJ, et al. Int J Clin Pract. 200761(7):1181‐1187. 2015;49(1):9‐16. What Patients Experience When Severe Potential Consequences of OIC OIC Occurs Fecal Impaction Hard Stools Incomplete Straining Evacuation Overflow Incontinence Bowel Ischemia Bloating Pain Infrequent Perforation Stools Camilleri M, et al. Am J Gastroenterol. 2011;106(3):497‐506.; Holzer P. Expert Opin Investig Drugs. 2007;16(2):181‐194. OIC –Often Underdiagnosed OIC Can Compromise Pain Management • Patient complaints regarding constipation may vary from one Patients missed, decreased, or stopped opioids….. individual to the next • Clinical measures of constipation, the number of bowel to get relief from opioid‐induced AEs 35% movements/week, do not often correlate with patients’ perception of what is regular 28% to avoid opioid‐induced AEs • Patients may deny yet meet clinical criteria for constipation • Patients may neglect or be embarrassed to discuss their to make it easier to have a bowel 33% constipation issues movement 0% 5% 10% 15% 20% 25% 30% 35% Assessing symptoms by talking to patients is the most efficient 92% of patients who decreased or stopped opioids experienced increased pain and cost‐effective way to determine the presence of OIC AEs=adverse events Coffin B, et al. Expert Rev Gastroenterol Hepatol. 2011;5(5):601‐613. Bell TJ, et al. Pain Med. 2009;10:35‐42. Burden and Cost of OIC Cost Burden With OIC Without OIC $23,631 • OIC has been found to represent a significant $25,000 ±$67,209 $16,923 economic cost burden, including impact on $20,000 $16,000 $12,652 $14,437 patient’s QOL and productivity $15,000 ±$38,191 $11,117 ±$22,897 ±$25,690 ±$19,717 $10,000 ±$19,525 $5,000 $‐ Nonelderly Elderly Long‐term care Recent study demonstrated patients with OIC had significantly more hospital admissions and longer inpatient stays than patients without OIC. The group with OIC had significantly higher costs per patient than those without. Wan Y, et al. Accessed at http://www.researchgate.net/publication/277143982_Economic_burden_of_opioid‐ Wan Y, et al Am Health Drug Benefits. 2015; 8(2): 93‐102. induced_constipation_among_long‐term_Opioid_users_with_non_cancer_pain. Accessed November 9, 2015. Work Productivity and Overall Patient Quality of Life Scores on Domains of Work Productivity and • Findings from a national What Tools Can Clinicians Use to Activity Impairment Questionnaire health and wellness OIC No OIC study demonstrated Measure and Monitor OIC? Worse * 68.1 70 that, when compared 56 with individuals without 60 * OIC, those individuals * 47.7 50 44.9 with OIC reported: 35.8 (%) ‒ Higher percentage of 40 33.1 * work time missed 30 22.6 Score ‒ Greater impairment 16.1 20 while working 10 ‒ Greater overall work impairment 0 ‒ Greater activity Better Work time Impairment Overall work Activity missed while impairment impairment impairment working *P<.05, OIC vs no OIC Bell TJ, et al. J Opioid Manag. 2009;5:137‐144. The Patient History: Summary: PRO Assessment Tool Asking the Right Questions Use in OIC Drug Development • Previous bowel pattern prior to starting opioids Assessment Tool Drug Development Program(s) in OIC Patients1 • Current pattern while taking opioids PAC‐SYM1 • PR oxycodone/naloxone PO • Stool frequency, consistency, and size • Methylnaltrexone SC • Degree of straining during defecation • Prucalopride POa,2 • History of delayed defecation • Alvimopan PO –OIC program discontinuedb,3,4 Stool Symptom Screener5 • None identified • Fiber intake • Fluid intake PAC‐QOL1 • Methylnaltrexone SC • Fruit and vegetable intake • Prucalopride POa,2 • Exercise – levels physical activity • Alvimopan PO –OIC program discontinuedb,3,4 BFI1 • PR oxycodone/naloxone PO BF‐Diary6 • IR tapentadol PO • Laxative use (frequency and types) a Approved in several countries (but not in the United States). b OIC program discontinued due to cardiovascular • Other medications (anticholinergics, calcium channel safety concerns. antagonists, iron supplements, calcium supplements) 1Gaertner J, et al. J Clin Gastroenterol. 2015;49(1):9‐16. 2Shire. www.shire.com/shireplc/en/products/ gastrointestinal/resolor. Accessed March 6, 2015.; 3Irving G, et al. J Pain. 2011;12(2):175‐184.; 4Sprawls KS, et al. Drugs in Development for Opioid‐Induced Constipation. Published March 7, 2012. 5Coyne KS, et al. [Published online September 18, 2014]. Patient. 6Camilleri M, et al. Am J Gastroenterol. 2011;106(3):497‐506. Tools for Patients • Bowel Function Index – Three‐item assessment – Assesses: . Ease of BM Current Therapeutic Approaches . BM completeness . Overall assessment – Score is mean of 3 items – Selected by AAPM consensus panel to be a good choice as a validated tool1 AAPM=American Academy of Pain Medicine 1Webster LR. Pain Med. 2015;16 Suppl 1:S16-21. Non‐Pharmacologic OTC Options: Constipation Therapies Current Therapy Falls Short
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