Tenapanor (Ibsrela) Form

Tenapanor (Ibsrela®, Xphozah®) is a sodium/hydrogen exchanger 3 (NHE3) inhibitor. FDA Approved Indication(s) Ibsrela is indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults. Xphozah is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. 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 Ibsrela and Xphozah are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Irritable Bowel Syndrome with Constipation (must meet all):

1. Request is for Ibsrela;
   2. Diagnosis of IBS-C;
   3. Age ≥ 18 years;
   4. 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 100 mg (2 tablets) per day. Approval duration: 12 months
   B. Hyperphosphatemia (must meet all):

4. Request is for Xphozah;

   2. Diagnosis of hyperphosphatemia associated with CKD;
   3. Member is on dialysis;
   4. Prescribed by or in consultation with a nephrologist;
   5. Age ≥ 18 years; Page 1 of 8

   CLINICAL POLICY Tenapanor

5. Member meets one of the following (a, b, c, or d):
   a. Failure (e.g., serum phosphorus > 5.5 mg/dL) of a 4-week trial of calcium acetate at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; b. Hypercalcemia as evidenced by recent (within the previous 30 days) corrected total serum calcium level > 10.2 mg/dL; c. Plasma parathyroid hormone (PTH) levels < 150 pg/mL on 2 consecutive measurements in the past 180 days; d. History of severe vascular and/or soft-tissue calcifications;
6. Failure (e.g., serum phosphorus > 5.5 mg/dL) of a 4-week trial of a non-calcium phosphate binder (e.g., lanthanum carbonate, sevelamer carbonate, see Appendix B) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated; *Prior authorization may be required for non-calcium phosphate binders
7. Xphozah is prescribed as add-on therapy to phosphate binder therapy;
   9. Dose does not exceed (a and b): a. 60 mg per day; b. 2 tablets per day. Approval duration: 12 months C. Other diagnoses/indications (must meet 1 or 2):
8. 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
9. 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 with Constipation (must meet all):

10. Request is for Ibsrela;

    2. 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);
    3. Member is responding positively to therapy;
    4. If request is for a dose increase, new dose does not exceed 100 mg (2 tablets) per day. Page 2 of 8

    CLINICAL POLICY Tenapanor Approval duration: 12 months B. Hyperphosphatemia (must meet all):

11. Request is for Xphozah;
    2. 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);
12. Member is responding positively to therapy (e.g., reduction in serum phosphorus from pretreatment level; maintenance of serum phosphorus level ≤ 5.5 mg/dL);
13. Xphozah is prescribed as add-on therapy to phosphate binder therapy;
    5. If request is for a dose increase, new dose does not exceed (a and b): a. 60 mg per day; b. 2 tablets per day. Approval duration: 12 months C. 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 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

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 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-C: irritable bowel syndrome with constipation NHE3: sodium/hydrogen exchanger 3 CKD: chronic kidney disease Page 3 of 8

    CLINICAL POLICY Tenapanor 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 6,000 mg/day Caplet: 12 caplets/day Powder: 6 grams/day 16 mcg/day
    1,500 mg/day total elemental calcium 4,500 mg/day 14 g/day psyllium (Metamucil®) calcium polycarbophil (FiberCon®) methylcellulose (Citrucel®) IBS-C
    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) IBS-C
    1,000 mg 1 to 4 times per day or as needed IBS-C
    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 lubiprostone (Amitiza®) IBS-C
    calcium acetate 8 mcg PO BID
    Hyperphosphatemia 2 capsules PO TID with meals; titrate to phosphorus < 6 mg/dL and calcium < 9.5 mg/dL lanthanum (Fosrenol®) Hyperphosphatemia sevelamer carbonate (Renvela®) 1,500 mg PO daily in divided doses; titrate by 750 mg/day every 2 to 3 weeks based on serum phosphorus level Hyperphosphatemia Starting dose for adult dialysis patients based on serum phosphorus level If serum phosphorus is:

    5.5 to < 7.5 mg/dL: 0.8 g PO TID w/ meals ≥ 7.5 mg/dL: 1.6 g PO TID w/ meals Starting dose for pediatric patients (6 years and older) based on body surface area (BSA) 0.75 to < 1.2: 0.8 g PO TID w/ meals 1.2: 1.6 g PO TID w/ meals Page 4 of 8

    CLINICAL POLICY Tenapanor Drug Name Dosing Regimen Dose Limit/ Maximum Dose Starting dose for patients switching from calcium acetate to Renvela based on calcium acetate 667 mg/capsule dosing schedule • Calcium acetate 1 capsule PO TID: Renvela 0.8 g PO TID w/ meals • Calcium acetate 2 capsules/tablets PO TID: Renvela 1.6 g PO TID w/ meals • Calcium acetate 3 capsules/tablets PO TID: Renvela 2.4 g PO TID w/ meals ferric citrate (Auryxia®) Hyperphosphatemia 12 tablets/day sevelamer hydrochloride (Renagel®) 13 g/day 2 tablets PO TID with meals; titrate by 1 to 2 tablets/day at 1-week or longer intervals based on serum phosphorus level Hyperphosphatemia Starting dose based on serum phosphorus level • > 5.5 to < 7.5 mg/dL: Renagel 800 mg - 1 tablet PO TID; 400 mg - 2 tablets PO TID w/meals • ≥ 7.5 to < 9 mg/dL: Renagel 800 mg - 2 tablets PO TID; 400 mg - 3 tablets PO TID w/meals • ≥ 9 mg/dL: Renagel 800 mg - 2 tablets PO TID; 400 mg - 4 tablets PO TID w/meals Starting dose for patients switching from calcium acetate to Renagel based on calcium acetate 667 mg/tablet dosing schedule • Calcium acetate 1 tablet PO TID: Renagel 800 mg - 1 tablet PO TID; 400 mg - 2 tabs PO TID • Calcium acetate 2 tablets PO TID: Renagel 800 mg - 2 tablets PO TID; 400 mg - 3 tabs PO TID • Calcium acetate 3 tablets PO TID: Renagel 800 mg - 3 tablets PO TID; 400 mg - 5 tablets PO TID sucroferric oxyhydroxide (Velphoro®) 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. Hyperphosphatemia 500 mg PO TID with meals 3,000 mg/day Page 5 of 8

    CLINICAL POLICY Tenapanor Appendix C: Contraindications/Boxed Warnings • Contraindication(s): patients < 6 years of age due to the risk of serious dehydration; patients with known or suspected mechanical gastrointestinal obstruction • Boxed warning(s) - Ibsrela only: contraindicated in patients < 6 years of age; avoid use of Ibsrela in patients 6 years to < 12 years of age; the safety and effectiveness of Ibsrela have not been established in patients < 18 years of age V. Dosage and Administration
    Indication IBS-C Hyper- phosphatemia Drug Name Ibsrela Xphozah Dosing Regimen 50 mg PO BID 30 mg PO BID before morning and evening meals Maximum Dose 100 mg/day 60 mg/day VI. Product Availability
    Drug Name Ibsrela Xphozah Availability Tablet: 50 mg Tablets: 10 mg, 20 mg, 30 mg VII.