Isavuconazonium (Cresemba) Form

Isavuconazonium (Cresemba®) is an azole antifungal.
FDA Approved Indication(s) Cresemba is indicated for the treatment of:
• • Invasive aspergillosis
Invasive mucormycosis Cresemba for injection is indicated in adults and pediatric patients 1 year of age and older. Cresemba capsules are indicated in adults and pediatric patients 6 years of age and older who weigh 16 kg and greater. 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 Cresemba is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Aspergillosis (must meet all):

1. Diagnosis of invasive aspergillosis;
   2. One of the following (a or b): a. Request for injection for intravenous administration: Age ≥ 1 year; b. Request for capsules or injection for nasogastric tube administration, both of the following (i and ii): i. Age ≥ 6 years; ii. Body weight ≥ 16 kg;
2. Prescribed by or in consultation with an infectious disease specialist, oncologist, or transplant specialist;
3. If age ≥ 2 years, failure of voriconazole at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;

4. Dose does not exceed one of the following (a or b): a. Adults (age ≥ 18 years) (i and ii): i. Loading dose: 372 mg every 8 hours for 48 hours (total 6 doses); ii. Maintenance dose: 372 mg per day; Page 1 of 8

   CLINICAL POLICY Isavuconazonium
   b. Pediatrics (age < 18 years): age- and weight-based loading and maintenance dose in section V, up to a maximum of 372 mg per day. Approval duration: 3 months B. Mucormycosis (must meet all):

5. Diagnosis of invasive mucormycosis;
   2. One of the following (a or b): a. Request for injection for intravenous administration: Age ≥ 1 year; b. Request for capsules or injection for nasogastric tube administration, both of the following (i and ii): i. Age ≥ 6 years; ii. Body weight ≥ 16 kg;
6. Prescribed by or in consultation with an infectious disease specialist;
   4. Dose does not exceed one of the following (a or b): a. Adults (age ≥ 18 years) (i and ii): i. Loading dose: 372 mg every 8 hours for 48 hours (total 6 doses); ii. Maintenance dose: 372 mg per day; b. Pediatrics (age < 18 years): age- and weight-based loading and maintenance dose in section V, up to a maximum of 372 mg per day. Approval duration: 3 months C. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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):

9. 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 8

   CLINICAL POLICY Isavuconazonium
   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 one of the following (a or b): a. Adults (age ≥ 18 years): 372 mg per day; b. Pediatrics (age < 18 years): age- and weight-based maintenance dose in section V, up to a maximum of 372 mg per day. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
10. 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

11. 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 FDA: Food and Drug Administration 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.
    Page 3 of 8

    Dose Limit/ Maximum Dose See regimen CLINICAL POLICY Isavuconazonium
    Drug Name Dosing Regimen voriconazole (Vfend®) Aspergillosis IV:
    • Adults, pediatric patients 12 to 14 years of age weighing ≥ 50 kg, and pediatric patients ≥ 15 years: 6 mg/kg IV every 12 hours for the first 24 hours, followed by 4 mg/kg IV every 12 hours • Pediatric patients 2 to < 12 years of age and 12 to 14 years of age weighing < 50 kg: 9 mg/kg IV every 12 hours for the first 24 hours, followed by 8 mg/kg IV every 12 hours PO:
    • Adults, pediatric patients 12 to 14 years of age weighing ≥ 50 kg, and pediatric patients ≥ 15 years: 200 mg PO every 12 hours beginning after at least 7 days of IV voriconazole therapy
    • Pediatric patients 2 to < 12 years of age and 12 to 14 years of age weighing < 50 kg: 9 mg/kg PO every 12 hours (maximum dose of 350 mg every 12 hours) beginning after at least 7 days of IV voriconazole therapy Clinical practice guidelines suggest voriconazole as primary therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. 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):
    o Hypersensitivity to Cresemba o Coadministration of strong CYP3A4 inhibitors, such as ketoconazole or high-dose ritonavir (400 mg every 12 hours), because strong CYP3A4 inhibitors can significantly increase the plasma concentration of isavuconazole o Coadministration of strong CYP3A4 inducers, such as rifampin, carbamazepine, St. John’s wort, or long acting barbiturates because strong CYP3A4 inducers can significantly decrease the plasma concentration of isavuconazole o Familial short QT syndrome. Cresemba shortened the QTc interval in a concentration-related manner • Boxed warning(s): none reported Page 4 of 8

    CLINICAL POLICY Isavuconazonium
    V. Dosage and Administration
    Indication Dosing Regimen Invasive aspergillosis, invasive mucormycosis Adults Loading dose: 372 mg (one vial IV, two 186 mg capsules PO, or five 74.5 mg capsules PO) every 8 hours for a total of 6 doses in 48 hours Maximum Dose Adults: Loading dose: 1,116 mg/day Maintenance dose (starting 12 to 24 hours after the last loading dose): 372 mg (1 vial IV, two 186 mg capsules PO, or five 74.5 mg capsules PO) QD Maintenance dose: 372 mg/day Pediatric patients • Loading dose is administered every 8 hours for a total of 6 doses in 48 hours • Maintenance dose is administered QD starting 12 to 24 hours after the last loading dose Pediatric patients: 372 mg/day
    Body weight Dose Age Cresemba for injection (372 mg vial): IV < 18 kg 1 to < 3 years < 37 kg 3 to < 18 years ≥ 37 kg Cresemba capsules (74.5 mg capsule): PO 6 to < 18 years 15 mg/kg 10 mg/kg 372 mg (1 vial) 16 to < 18 kg 18 to < 25 kg 25 to < 32 kg ≥ 32 kg 149 mg (2 capsules) 223.5 mg (3 capsules) 298 mg (4 capsules) 372 mg (5 capsules) Cresemba for injection may also be administered via nasogastric tube administration in patients who are 6 years of age and older and weighing 16 kg and greater.
    VI. Product Availability
    • Capsule: 186 mg of isavuconazonium sulfate (equivalent to 100 mg of isavuconazole), 74.5 mg of isavuconazonium sulfate (equivalent to 40 mg of isavuconazole) • Single-dose vial for injection: 372 mg of isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) VII.