Alosetron (Lotronex) Form

Alosetron (Lotronex®) is a selective serotonin 5-HT3 antagonist. FDA Approved Indication(s) Lotronex is indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have:
• Chronic IBS symptoms (generally lasting 6 months or longer) • Had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and
• Not responded adequately to conventional therapy Diarrhea-predominant IBS is severe if it includes diarrhea and 1 or more of the following:
• Frequent and severe abdominal pain/discomfort • Frequent bowel urgency or fecal incontinence • Disability or restriction of daily activities due to IBS Limitation(s) of use:
• Because of infrequent but serious gastrointestinal adverse reactions associated with Lotronex, the indication is restricted to those patients for whom the benefit‑to‑risk balance is most favorable. • Clinical studies have not been performed to adequately confirm the benefits of Lotronex in men.
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) 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 – Diarrhea (must meet all):

1. Diagnosis of diarrhea-predominant IBS;

   2. Age ≥ 18 years;
   3. Failure of an anti-diarrheal agent (e.g., loperamide) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated;
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   CLINICAL POLICY Alosetron

2. Failure of an antispasmodic agent (e.g., dicyclomine) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated;
3. If request is for brand Lotronex, member must use generic alosetron, unless contraindicated or clinically significant adverse effects are experienced;
4. Dose does not exceed 2 mg (2 tablets) per day. Approval duration:
   Medicaid – 12 months
   Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
5. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial and CP.PMN.16 for Medicaid; or
6. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Irritable Bowel Syndrome – Diarrhea (must meet all):
7. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
   2. Member is responding positively to therapy;
   3. If request is for brand Lotronex, member must use generic alosetron, unless contraindicated or clinically significant adverse effects are experienced;
8. If request is for a dose increase, new dose does not exceed 2 mg (2 tablets) per day. Approval duration:
   Medicaid – 12 months Commercial – 12 months or duration of request, whichever is less
   B. Other diagnoses/indications (must meet 1 or 2):

9. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): Page 2 of 7

   CLINICAL POLICY Alosetron a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial and CP.PMN.16 for Medicaid; or

10. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial and CP.PMN.53 for Medicaid.
    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 policies – CP.CPA.09 for commercial and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration IBS: irritable bowel syndrome Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose If no clinical improvement after treatment with 16 mg/day for at least 10 days, symptoms are unlikely to be controlled by further use. 20 mg/day (of diphenoxylate)
    160 mg/day (40 mg PO QID) 1.5 mg/day loperamide (Imodium A-D) Adults: 4 mg PO followed by 2 mg after each unformed stool until diarrhea is resolved; then individualize dose. Administer optimal daily dose (4-8 mg) as single or divided doses. diphenoxylate/atropine (Lomotil)
    Initially, 5 mg (2 tablets) PO QID; Discontinue after 10 days if clinical improvement is not observed dicyclomine (Bentyl) Adults: 20 mg PO QID up to 1 week, then increase to 40 mg PO QID hyoscyamine (Levsin, Levbid) Adults: Levsin: 0.125 – 0.25 mg PO Q 4h Levbid: 0.375 – 0.75 mg PO Q 12h Page 3 of 7

    CLINICAL POLICY Alosetron 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
    o Lotronex should not be initiated in patients with constipation o History of chronic or severe constipation or sequelae from constipation; intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, and/or adhesions; ischemic colitis; impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; Crohn’s disease or ulcerative colitis; diverticulitis; severe hepatic impairment o Concomitant use of fluvoxamine • Boxed warning(s): serious gastrointestinal adverse reactions (including ischemic colitis and serious complications of constipation) have resulted in hospitalization and rarely, blood transfusion, surgery, and death Appendix D: General Information • 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. The Lotronex REMS program was implemented to help reduce the risks of a serious gastrointestinal (GI) adverse event and to ensure the benefits of the drug outweigh the risk. • One study of 662 men with diarrhea-predominant IBS showed Lotronex 1 mg 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. V. Dosage and Administration
    Indication Dosing Regimen IBS • Starting dose is 0.5 mg PO BID
    • May increase dose to 1 mg BID after 4 weeks if starting dosage is well tolerated but does not adequately control IBS symptoms • Discontinue Lotronex in patients who have not had adequate control of IBS symptoms after 4 weeks of treatment with 1 mg BID Maximum Dose 2 mg/day VI. Product Availability
    Tablets: 0.5 mg, 1 mg VII.