CORLANOR, Ivabradine HCl Form

Ivabradine (Corlanor®) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker. FDA Approved Indication(s) Corlanor is indicated: • To reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction (LVEF) ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use; • For the treatment of stable symptomatic heart failure due to dilated cardiomyopathy (DCM) in pediatric patients aged 6 months and older, who are in sinus rhythm with an elevated heart rate. 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 Corlanor is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Heart Failure (must meet all):

1. Diagnosis of chronic heart failure;
   2. Prescribed by or in consultation with a cardiologist;
   3. Age ≥ 6 months;
   4. LVEF ≤ 35% for adults or ≤ 45% for pediatrics;
   5. Member is in sinus rhythm with a resting heart rate of one of the following (a, b, c, or d): a. Age ≥ 6 to ≤ 12 months: ≥ 105 beats per minute; b. Age > 1 to < 3 years: ≥ 95 beats per minute; c. Age ≥ 3 to < 5 years: ≥ 75 beats per minute; d. Age 5 years and older: ≥ 70 beats per minute;

2. Failure of two of the following beta-blockers recommended for heart failure at up to maximally indicated doses, each used for ≥ 30 days, unless clinically significant adverse effects are experienced or all are contraindicated: bisoprolol, carvedilol (immediate- or extended-release), extended-release metoprolol succinate; Page 1 of 7

   CLINICAL POLICY Ivabradine

3. Member has used one of the aforementioned beta blockers for ≥ 30 days within the past 60 days, unless clinically significant adverse effects are experienced or all are contraindicated;
4. Dose does not exceed both of the following (a and b):
   a. 15 mg per day;
   b. 2 tablets per day or 15 mL per day. Approval duration:
   HIM – 12 months Medicaid/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, 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. Heart Failure (must meet all):
7. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Corlanor for heart failure and has received this medication for at least 30 days;
8. Member is responding positively to therapy;
   
   3. If request is for a dose increase, new dose does not exceed both of the following (a and b):
      a. 15 mg per day;
      b. 2 tablets or 15 mL per day.
      Approval duration:
      HIM – 12 months Medicaid/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 Ivabradine 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

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, 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 DCM: dilated cardiomyopathy FDA: Food and Drug Administration LVEF: left ventricular ejection fraction 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 Beta-Blockers Recommended for Heart Failure bisoprolol carvedilol (Coreg®, Coreg CR®) Heart Failure† Initially, 1.25 mg PO QD for 48 hours, then 2.5 mg QD for the first month, then 5 mg QD. Heart Failure Immediate-release: Initially, 3.125 mg PO BID for 2 weeks. Dosage may be subsequently increased to 6.25, 12.5, and then 25 mg PO BID over successive intervals of at least 2 weeks. 10 mg/day Immediate-release: 100 mg/day Extended-release: 80 mg/day Extended-release: Initially, 10 mg PO QD for 2 weeks. Dosage may be subsequently Page 3 of 7

    CLINICAL POLICY Ivabradine Drug Name Dosing Regimen metoprolol succinate extended release (Toprol XL®) increased to 20, 40, and then 80 mg PO QD over successive intervals of at least 2 weeks. Heart Failure 25 mg PO QD for 2 weeks in patients with NYHA class II heart failure, or 12.5 mg PO QD in patients with more severe heart failure. Double the dose every 2 weeks as tolerated, up to the target dosage of 200 mg PO QD. Dose Limit/ Maximum Dose 200 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. †Off-label indication Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
    o Acute decompensated heart failure o Clinically significant hypotension o Sick sinus syndrome, sinoatrial block, or 3rd degree AV block, unless a functioning demand pacemaker is present o Clinically significant bradycardia o Severe hepatic impairment
    o Pacemaker dependence (heart rate maintained exclusively by the pacemaker) o Concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors
    • Boxed warning(s): none reported V. Dosage and Administration
    Indication Heart failure Dosing Regimen Adult and pediatric patients ≥ 40 kg: Initially 2.5 mg (pediatrics and vulnerable adults) or 5 mg PO BID. After 2 weeks of treatment, adjust dose based on heart rate. The maximum dose is 7.5 mg BID. Maximum Dose 15 mg/day Pediatric patients < 40 kg: Initially 0.05 mg/kg PO BID. Adjust dose at 2-week intervals by 0.05 mg/kg based on heart rate. VI. Product Availability
    • Tablets: 5 mg, 7.5 mg • Oral solution: 5 mg/5 mL VII.