AMITIZA, Lubiprostone Form

Lubiprostone (Amitiza®) is a chloride channel activator. FDA Approved Indication(s) Amitiza is indicated for the treatment of: • Chronic idiopathic constipation (CIC) in adults • • Opioid-induced constipation (OIC) in adults with chronic, non-cancer pain, including Irritable bowel syndrome with constipation (IBS-C) in women ≥ 18 years old patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.
o Limitation(s) of use: Effectiveness of Amitiza in the treatment of OIC in patients taking diphenylheptane opioids (e.g., methadone) has not been established. 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 Amitiza is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Idiopathic Constipation (must meet all):

1. Diagnosis of CIC;
   2. Age ≥ 18 years;
   3. Failure of one bulk forming laxative (e.g., psyllium (Metamucil®), methylcellulose (Citrucel®), calcium polycarbophil (FiberCon®)) unless clinically significant adverse effects are experienced or all are contraindicated;
2. Failure of one stimulant laxative (e.g., bisacodyl, senna) unless clinically significant adverse effects are experienced or all are contraindicated;
3. Failure of polyethylene glycol (MiraLax®) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects experienced;
4. Member must use generic lubiprostone, unless contraindicated or clinically significant adverse effects are experienced;

5. Dose does not exceed both of the following (a and b):
   a. 48 mcg per day;
   b. 2 capsules per day. Approval duration: 12 months
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   CLINICAL POLICY Lubiprostone B. Irritable Bowel Syndrome with Constipation (must meet all):

6. Diagnosis of IBS-C;
   2. Age ≥ 18 years;
   3. Failure of one bulk forming laxative (e.g., psyllium (Metamucil), methylcellulose (Citrucel), calcium polycarbophil (FiberCon)) unless clinically significant adverse effects are experienced or all are contraindicated;
7. Member must use generic lubiprostone, unless contraindicated or clinically significant adverse effects are experienced;
8. Dose does not exceed both of the following (a and b):
   a. 16 mcg per day;
   b. 2 capsules per day. Approval duration: 12 months
   C. Opioid-Induced Constipation (must meet all):
9. Diagnosis of OIC;
   2. Age ≥ 18 years;
   3. Member has been taking opioid(s) for ≥ 4 weeks due to chronic pain, not caused by active cancer;
10. Failure of one agent from each of the following classes while on opioid therapy, unless clinically significant adverse effects are experienced or all are contraindicated (a, b, and c): a. Stimulant laxative (e.g., bisacodyl, senna); b. Osmotic laxative (e.g., lactulose, polyethylene glycol); c. Stool softener (e.g., docusate);
11. Member has used one of the aforementioned agents in the past 30 days, unless contraindicated;
12. Member must use generic lubiprostone, unless contraindicated or clinically significant adverse effects are experienced;
13. Dose does not exceed both of the following (a and b): a. 48 mcg per day;
    b. 2 capsules per day. Approval duration: 6 months
    D. Other diagnoses/indications (must meet 1 or 2):

14. 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, HIM.PA.33 for health insurance marketplace, 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, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or Page 2 of 8

    CLINICAL POLICY Lubiprostone

15. 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, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    II. Continued Therapy A. All Indications in Section I (must meet all):
16. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria;
17. 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);
18. Member is responding positively to therapy;
    4. Member must use generic lubiprostone, unless contraindicated or clinically significant adverse effects are experienced;
19. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. IBS-C (i and ii):
    i. 16 mcg per day; ii. 2 capsules per day; b. CIC or OIC (i and ii):
    i. 48 mcg per day;
    ii. 2 capsules per day. Approval duration: 12 months
    B. Other diagnoses/indications (must meet 1 or 2):
20. 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, HIM.PA.33 for health insurance marketplace, 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, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

21. 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, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
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    CLINICAL POLICY Lubiprostone 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, HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid, or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CIC: chronic idiopathic constipation FDA: Food and Drug Administration PAMORA: peripherally acting mu- opioid receptor antagonist IBS-C: irritable bowel syndrome with constipation OIC: opioid-induced constipation 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 7.2 g (as soluble dietary fiber)/day 5,000 mg/day calcium polycarbophil Caplet: 12 caplets/day Powder: 6 g/day 15 mg/day PO; 10 mg/day rectally 8 tablets/day (68.8 mg sennosides/day) 40 g/day (60 mL or 2 to 4 packets/day) psyllium (Metamucil®) calcium polycarbophil (FiberCon®) methylcellulose (Citrucel®) bisacodyl (Dulcolax®) senna (Senokot®) lactulose 1 rounded teaspoonful, tablespoonful, or premeasured packet in 240 mL of fluid PO 1 to 3 times per day (2.4 g of soluble dietary fiber per dose) 1,250 mg calcium polycarbophil 1 to 4 times PO per day or as needed Caplet: 2 caplets (total 1 g methylcellulose) PO with at least 240 mL (8 oz) of liquid, up to 6 times per day as needed Powder: 1 heaping tablespoonful (2 g methylcellulose per 19 g powder) in at least 240 mL (8 oz) of water PO, given 1 to 3 times per day as needed Oral: 5 to 15 mg QD Rectal: Enema, suppository: 10 mg (1 enema or suppository) QD 1 to 2 tablets (8.6 to 17.2 mg sennosides) PO BID 10 to 20 g (15 to 30 mL or 1 to 2 packets) PO QD; may increase to 40 g (60 mL or 2 to 4 packets) QD if necessary Page 4 of 8

    CLINICAL POLICY Lubiprostone Drug Name Dosing Regimen polyethylene glycol 3350 (MiraLax®) docusate sodium (Colace®) 17 g (approximately 1 heaping tablespoon) of powder in 120 to 240 mL of fluid given PO QD 50 to 300 mg/day PO given in single or divided doses Dose Limit/ Maximum Dose 34 g/day 360 mg/day 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): patients with known or suspected mechanical gastrointestinal obstruction
    • Boxed warning(s): none reported V. Dosage and Administration
    Indication CIC and OIC IBS-C Dosing Regimen 24 mcg PO BID 8 mcg PO BID Maximum Dose 48 mcg/day 16 mcg/day VI. Product Availability
    Capsules: 8 mcg and 24 mcg VII.