LINZESS, Linaclotide Form

Linaclotide (Linzess®) is a guanylate cyclase-C agonist. FDA Approved Indication(s) Linzess is indicated for the treatment of:
• • Chronic idiopathic constipation (CIC) in adults • Functional constipation (FC) in pediatric patients 6 to 17 years of age Irritable bowel syndrome with constipation (IBS-C) in adults Policy/Criteria Provider must submit documentation (including 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 Linzess is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Irritable Bowel Syndrome with Constipation (must meet all):

1. 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;
2. Failure of generic lubiprostone, unless contraindicated or clinically significant adverse effects are experienced;
3. Dose does not exceed both of the following (a and b):
   a. 290 mcg per day;
   b. 1 capsule per day. Approval duration: 12 months B. Chronic Idiopathic Constipation (must meet all):

4. 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; Page 1 of 7

   CLINICAL POLICY Linaclotide

5. Failure of one stimulant laxative (e.g., bisacodyl, senna), unless clinically significant adverse effects are experienced or all are contraindicated;
6. Failure of polyethylene glycol (MiraLax®) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
   
   6. Failure of generic lubiprostone, unless contraindicated or clinically significant adverse effects are experienced;
7. Dose does not exceed both of the following (a and b) a. 145 mcg per day;
   b. 1 capsule per day. Approval duration: 12 months
   C. Functional Constipation (must meet all):
8. Diagnosis of FC;
   2. Age ≥ 6 to ≤ 17 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;
9. Failure of polyethylene glycol (MiraLax®) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
10. Failure of at least ONE of the following (a, b, or c), unless clinically significant adverse effects are experienced or all are contraindicated:
    a. Stimulant laxative (e.g., bisacodyl, senna);
    b. Osmotic laxative (e.g., lactulose, magnesium hydroxide);
    c. Lubricant laxative (e.g., mineral oil);
11. Dose does not exceed 72 mcg (1 capsule) per day. Approval duration: 12 months
    D. Other diagnoses/indications (must meet 1 or 2):
12. 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.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.PMN.16 for Medicaid; or
13. 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.PMN.53 for Medicaid.
    II. Continued Therapy A. All Indications in Section I (must meet all):

14. Member meets one of the following (a or b): Page 2 of 7

    CLINICAL POLICY Linaclotide 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 a dose increase, new dose does not exceed any of the following (a, b, or c): a. IBS-C (i and ii):
       i. 290 mcg per day;
       ii. 1 capsule per day;
       b. CIC (i and ii):
       i. 145 mcg per day;
       ii. 1 capsule per day;
       c. FC: 72 mcg (1 capsule) per day; Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):
15. 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.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.PMN.16 for Medicaid; or

16. 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.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.PMN.53 for Medicaid or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CIC: chronic idiopathic constipation
    FC: functional constipation
    FDA: Food and Drug Administration IBS-C: irritable bowel syndrome with constipation
    Page 3 of 7

    CLINICAL POLICY Linaclotide 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 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) 1,000 mg 1 to 4 times per day or as needed 6,000 mg/day Dose Limit/ Maximum Dose 7.2 g (as soluble dietary fiber)/day psyllium (Metamucil®) calcium polycarbophil (FiberCon®) methylcellulose (Citrucel®) sennosides (Senokot®) bisacodyl (Dulcolax®) polyethylene glycol 3350 (MiraLax®) magnesium hydroxide (milk of magnesia) mineral oil 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 1 to 2 tablets (8.6 to 17.2 mg sennosides) PO BID 5 to 15 mg/day (1 to 3 tablets) PO given as a single dose, or 1 suppository or retention enema (10 mg) PR QD Caplet: 12 caplets/day Powder: 6 grams/day 68.8 mg sennosides/day 15 mg/day PO or 10 mg/day PR Either a suppository or oral tablet(s) may be used up to 3 times per week 17 g (approximately 1 heaping tablespoon) of powder in 120 to 240 mL of fluid PO QD Varies
    34 grams/day
    Varies
    10 mL to 90 mL per day PO as needed to relieve constipation
    90 mL/day PO or 120 mL/day PR
    lubiprostone (Amitiza®) 60 mg mL or 120 mL rectally as a single dose CIC: 24 mcg PO BID IBS-C: 8 mcg PO BID CIC: 48 mcg/day IBS-C: 16 mcg/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. Page 4 of 7

    CLINICAL POLICY Linaclotide Appendix C: Contraindications/Boxed Warnings • Contraindication(s): patients less than 2 years of age; patients with known or suspected mechanical gastrointestinal obstruction • Boxed warning(s): risk of serious dehydration in pediatric patients less than 2 years of age V. Dosage and Administration
    Indication IBS-C CIC FC Dosing Regimen 290 mcg PO QD 72 mcg or 145 mcg PO QD 72 mcg PO QD VI. Product Availability
    Capsules: 72 mcg, 145 mcg, and 290 mcg Maximum Dose 290 mcg/day 145 mcg/day 72 mcg/day VII.