Clinical Policy: Alosetron (Lotronex) Reference Number: CP.CPA.65 Effective Date: 11.16.16 Last Review Date: 11.17 Revision Log Line of Business: Medicaid – Medi-Cal See Important Reminder at the end of this policy for important regulatory and legal information. Description Alosetron (Lotronex™) is a potent and selective antagonist of the serotonin 5-HT3 receptor type. FDA approved indication Lotronex is indicated: • For the treatment of women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have: o Chronic IBS symptoms (generally lasting 6 months or longer), o Had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and o Not responded adequately to conventional therapy. • Severe IBS includes diarrhea and 1 or more of the following: o Frequent and severe abdominal pain/discomfort, o Frequent bowel urgency or fecal incontinence, o Disability or restriction of daily activities due to IBS. Policy/Criteria Provider must submit documentation (which may include office chart notes and lab results) supporting that member has met all approval criteria It is the policy of health plans affiliated with Centene Corporation® that Lotronex is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Irritable Bowel Syndrome (IBS) (must meet all): 1. Diagnosis of severe diarrhea-predominant IBS confirmed by all of the following (a, b, and c): a. Frequent and severe abdominal pain/discomfort (at least 6 months); b. Frequent bowel urgency or fecal incontinence (> 3 times per day); c. Disability or restriction of daily activities due to IBS . 2. Physician is enrolled in the Prescribing Program for Lotronex; 3. Patient has read and signed the Patient Acknowledgment Form for Lotronex; 4. IBS symptoms are chronic and recurrent (lasting 6 months or longer); 5. Physician has ruled out anatomic or biochemical abnormalities of the gastrointestinal (GI) tract. Documentation may be required on any of the following: GI consult notes including reports from diagnostic procedures (e.g. colonoscopy or sigmoidoscopy). Complete blood count (CBC), and thyroid stimulating hormone (TSH) to rule out other causes; Page 1 of 6 CLINICAL POLICY Alosetron 6. Failure of or clinically significant adverse effects to all of the following (a, b, and c): a. Conventional therapy (e.g. psyllium (Metamucil)) for the last 1-2 months; b. Anti-diarrhea agent; c. Antispasmodic agent; 7. Dose does not exceed: 2 mg/day. Approval duration: Length of Benefit B. Other diagnoses/indications 1. Refer to CP.PMN.53 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized). II. Continued Therapy A. Irritable Bowel Syndrome (IBS) (must meet all): 1. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; 2. Member is responding positively to therapy; 3. If request is for a dose increase, new dose does not exceed 2 mg/day. Approval duration: Length of Benefit III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy – CP.PMN.53 or evidence of coverage documents; B. History of chronic or severe constipation or sequelae from constipation; intestinal obstruction, stricture, toxic megacolon, GI perforations/adhesions; ischemic colitis; impaired intestinal circulation, thrombophlebitis, hypercoagulable state; Crohn’s disease or ulcerative colitis; diverticulitis; severe hepatic impairment; C. Do not initiate in patients with constipation; D. Concomitant use of fluvoxamine. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key – N/A Appendix B: General Information • Lotronex should be discontinued immediately in patients who develop constipation or symptoms of ischemic colitis. Patients should immediately report constipation or symptoms of ischemic colitis to their physician. Lotronex should not be resumed in patients who develop ischemic colitis. Patients who have constipation should immediately contact their physician if the constipation does not resolve after Lotronex is discontinued. Patients with resolved constipation should resume Lotronex only on the advice of their treating physician. • Concomitant administration of Lotronex with fluvoxamine is contraindicated. Fluvoxamine, a known strong inhibitor of CYP1A2, has been shown to increase mean Lotronex plasma concentrations approximately 6-fold and prolong the half-life by approximately 3-fold. Page 2 of 6 CLINICAL POLICY Alosetron • Infrequent but serious GI adverse events have been reported with the use of Lotronex. These events, including ischemic colitis and serious complications of constipation, have resulted in hospitalization, and rarely, blood transfusion, surgery, and death. • One study of 662 men with diarrhea-predominant IBS showed Lotronex 1mg twice daily provided a significantly higher average rate of adequate relief of IBS pain and discomfort during weeks 5-12 of the treatment phase (primary endpoint) compared to placebo. • Commercially available Lotronex is prescribed and distributed under a restricted distribution program, which is intended to control its access and to educate program participants (clinicians, pharmacists, patients) about the risks and benefits of the drug. Prescribers must enroll in the Prometheus Prescribing Program for Lotronex by calling 1- 888-423-5227 or visiting http://www.lotronexppl.com to complete the Prescriber Enrollment Form. • The Prescribing Program for Lotronex was implemented to help reduce the risk of serious GI adverse events. Only physicians who have enrolled in the Prescribing Program for Lotronex, based on their understanding of the benefits and risks, can prescribe Lotronex. • Before receiving the initial prescription for Lotronex, the patient must read and sign the Patient Acknowledgment Form for Lotronex. Lotronex should not be used by patients who are unable to understand or comply with the Patient Acknowledgment Form for Lotronex. Appendix C: Therapeutic Alternatives Drug Dosing Regimen Dose Limit/Maximum Dose Anti-diarrhea agents diphenoxylate/ Initial dose 2 tablets (5 mg of If no clinical improvement after atropine diphenoxylate) PO QID. treatment with 20 mg/day (of (Lomotil) Individualize dose. diphenoxylate) for at least 10 days, symptoms are unlikely to be controlled by further use. loperamide Adults: 4 mg PO followed by 2 If no clinical improvement after (Imodium A- mg after each unformed stool treatment with 16 mg/day for at least 10 D) until diarrhea is resolved; then days, symptoms are unlikely to be individualize dose. controlled by further use. Administer optimal daily dose (4-8 mg) as single or divided doses. Antispasmodic/anticholinergic agents dicyclomine Adults: 20 mg PO QID up to 1 160 mg/day (40 mg PO QID) (Bentyl) week, then increase to 40 mg PO QID hyoscyamine Adults: 1.5 mg/day (Levsin, Levsin: 0.125 – 0.25 mg PO Q Levbid) 4h Page 3 of 6 CLINICAL POLICY Alosetron Drug Dosing Regimen Dose Limit/Maximum Dose Levbid: 0.375 – 0.75 mg PO Q 12h Donnatal, Adults: Donnatal: 8 tablets (40 ml)/day Donnatal Donnatal: 1-2 tablets or 5-10 ml Donnatal Extentabs: 3 tablets/day Extentabs of elixir PO TID-QID (hyoscyamine, atropine, Donnatal Extentabs: 1 tablet PO scopolamine, Q 12h; may increase to 1 tablet phenobarbital PO Q 8h if needed Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. * Requires Prior Authorization V. Dosage and Administration Indication Dosing Regimen Maximum Dose Irritable Bowel Syndrome • Starting dose should be 1 mg twice a day (IBS) 0.5 mg PO BID • After 4 weeks dosage can be increased to 1 mg PO BID if well tolerated but symptoms not controlled • Therapy to be stopped if symptoms are not controlled after 4 weeks of 1 mg PO BID therapy VI. Product Availability Drug Availability Lotronex Tablets: 0.5 mg, 1 mg VII. References 1. Lotronex [Prescribing Information] San Diego, CA: Prometheus Laboratories, Inc; March 2014. Available at: www.lotronexppl.com Accessed January 13, 2017 2. Irritable Bowel Syndrome Self Help and Support Group. Diagnostic Criteria. Available at: http://www.ibsgroup.org/diagnosis. Accessed January 13, 2017. 3. Rome Foundation. Rome III Criteria for IBS. Available at: http://www.romecriteria.org/assets/pdf/20_RomeIII_apB_899-916.pdf. Accessed January 13, 2017. 4. Chey WD, Chey WY, Heath AT, et al. Long-term safety and efficacy of alosetron in women with severe diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 2004;99(11):2195-203. 5. Chang L, Amen VZ, Dukes GE, et al. A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS. Am J Gastroentrol. 2005;100(1):115-23. Page 4 of 6 CLINICAL POLICY Alosetron 6. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed January 13, 2017. 7. Lotronex. American Hospital Formulary Service Drug Information. Available at: http://medicinescomplete/com/mc/ahsf/current/. Accessed January 13, 2017. Reviews, Revisions, and Approvals Date P&T Approval Date Converted to new template. Minor changes to verbiage and 1.10.17 11.17 grammar. References updated. Important Reminder This clinical policy has been developed by appropriately experienced and licensed