JYNARQUE, Tolvaptan SAMSCA, Tolvaptan Form

Tolvaptan (Jynarque®, Samsca®) is a selective vasopressin V2-receptor antagonist. FDA Approved Indication(s) Jynarque is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD). Samsca is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium < 125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and syndrome of inappropriate antidiuretic hormone (SIADH). Limitation(s) of use:
• Patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological symptoms should not be treated with Samsca. It has not been established that Samsca provides a symptomatic benefit to patients. • 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 Jynarque and Samsca are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Autosomal Dominant Polycystic Kidney Disease (must meet all):

1. Diagnosis of ADPKD;
   2. Request is for Jynarque;
   3. Prescribed by or in consultation with a nephrologist;
   4. Age ≥ 18 years;
   5. Dose does not exceed 120 mg per day. Approval duration: Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less. B. Hyponatremia (must meet all):

2. Diagnosis of hypervolemic or euvolemic hyponatremia; Page 1 of 7

   CLINICAL POLICY Tolvaptan

3. Request is for Samsca;
   3. Prescribed by or in consultation with a nephrologist, cardiologist, or endocrinologist;
   4. Recent (within the last 7 days) serum sodium level < 125 mEq/L, unless hyponatremia is symptomatic and has resisted correction with fluid restriction;
4. Age ≥ 18 years;
   
   6. Member must use generic tolvaptan, unless contraindicated or clinically significant adverse effects are experienced;
   7. Dose does not exceed 60 mg per day. Approval duration: 30 days C. 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, 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
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, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Autosomal Dominant Polycystic Kidney Disease (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 a dose increase, new dose does not exceed 120 mg per day. Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less. B. Hyponatremia (must meet all):

8. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; Page 2 of 7

   CLINICAL POLICY Tolvaptan 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);

9. Member is responding positively to therapy as evidenced by increased sodium level since baseline;
10. Member has not received more than 30 days of Samsca treatment;
    4. Member must use generic tolvaptan, unless contraindicated or clinically significant adverse effects are experienced;
11. If request is for a dose increase, new dose does not exceed 60 mg/day. Approval duration: up to a total duration of 30 days C. 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.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

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.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, 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, 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 ADPKD: autosomal dominant polycystic kidney disease FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
    Not applicable Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Jynarque: Page 3 of 7

    CLINICAL POLICY Tolvaptan  History, signs or symptoms of significant liver impairment or injury, does not include uncomplicated polycystic liver disease; concomitant use of strong CYP 3A inhibitors is contraindicated; uncorrected abnormal blood sodium concentrations; unable to sense or respond to thirst; hypovolemia; hypersensitivity to tolvaptan or any of its components; uncorrected urinary outflow obstruction; anuria. o Samsca:  Use in patients with ADPKD outside of FDA-Approved REMS; patients who are unable to respond appropriately to thirst; hypovolemic hyponatremia; concomitant use of strong CYP 3A inhibitors; anuria; hypersensitivity. • Boxed warning(s): o Jynarque:
     Risk of serious liver injury, acute liver failure requiring liver transplantation has been reported; measure transaminases and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then continuing monthly for the first 18 months and every 3 months thereafter, Jynarque is only available through a restricted distribution program called Jynarque REMS program.
    o Samsca:  Initiate and re-initiate in a hospital and monitor serum sodium; not for use for ADPKD. V. Dosage and Administration
    Drug Name Indication Tolvaptan (Jynarque) ADPKD Dosing Regimen 60 mg PO per day administered as 45 mg in the morning and 15 mg 8 hours later.
    Maximum Dose 120 mg/day Tolvaptan (Samsca) hyponatremia 60 mg/day If dose is tolerated after at least a week, the total daily dose of 90 mg (60 mg in the morning and 30 mg 8 hours later) can be given.
    The target dose is 120 mg/day (90 mg in the morning and 30 mg 8 hours later), if tolerated. 15 mg PO once daily, then 30 mg PO once daily after 24 hours, to a maximum of 60 mg PO once daily as needed to achieve the desired level of serum sodium. Samsca initiation and re-initiation should occur in a hospital. Do not administer Samsca for more than 30 days to minimize the risk of liver injury.
    Page 4 of 7

    CLINICAL POLICY Tolvaptan VI. Product Availability
    Drug Name Tolvaptan (Jynarque) Availability Tablets (7-day and 28-day blister-packs): 45 mg with 15 mg, 60 mg with 30 mg, 90 mg with 30 mg Tolvaptan (Samsca) Tablets (30 pack): 15 mg, 30 mg Tablets: 15 mg, 30 mg (generic available) VII.