CurrentEmblemHealthPolicy MG.MM.PH.209

Cresemba® (isavuconazonium sulfate) Intravenous

Covers medical necessity, dosing, and authorization criteria for intravenous Cresemba for treatment of invasive aspergillosis and invasive mucormycosis for EmblemHealth members.

Policy Summary

PayerEmblemHealth

PolicyCresemba® (isavuconazonium sulfate) Intravenous

Policy CodePolicy MG.MM.PH.209

Change TypeAdded Medicaid coverageICD-10 updates

Effective Date

Next Review Date

Key ActionSubmit prior authorization with clinical evidence demonstrating diagnosis of invasive aspergillosis or invasive mucormycosis and meeting medical necessity criteria.

SourceLink

POLICY UPDATE CHANGES

Added coverage back to our Medicaid population, updated title to include 'intravenous' and removed 18 years and older limitation.

Removed coverage from our Medicaid population.

Annual Review: updates ICD-10 codes.

3 monthsauthorization length

11,904max billable units/28d

J1833HCPCS

00469-0420-xxNDC

Coverage and Medical Necessity Criteria

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Initial Approval Criteria

Covered when ALL of the following are met:

Microbiology and documentation: Specimens for fungal culture and other relevant laboratory studies (including histopathology) to isolate and identify causative organism(s) should be obtained prior to initiating antifungal therapy; therapy may be started before results are available but must be adjusted when results become available.

Diagnoses: Member must have a diagnosis of either Invasive Aspergillosis OR Invasive Mucormycosis.

Includes specified ICD-10 codes listed in the coding section.

Renewal Criteria

Renewal requires:

Continuation: Patient continues to meet INITIAL APPROVAL CRITERIA.

Authorization length is three months and may be renewed.

Cresemba (isavuconazonium sulfate) is contraindicated in individuals with a known hypersensitivity to isavuconazole. Requests for coverage should be denied when documented allergy or hypersensitivity to isavuconazole exists.

Coadministration with agents that strongly affect CYP3A4 is contraindicated: strong CYP3A4 inhibitors (for example, ketoconazole or high‑dose ritonavir 400 mg every 12 hours) can significantly increase isavuconazole plasma concentrations and are not permitted; likewise, strong CYP3A4 inducers (for example, rifampin, carbamazepine, St. John's wort, or long‑acting barbiturates) can significantly decrease isavuconazole plasma concentrations and are not permitted.

Cresemba is contraindicated in patients with familial short QT syndrome because isavuconazole shortens the QTc interval in a concentration‑related manner. These contraindications and drug interaction risks represent exclusions to coverage.

Therapy with Cresemba is not considered medically necessary if the member demonstrates disease progression while on Cresemba; such progression is a basis for denying continued coverage.

Use of Cresemba for indications that are not supported by CMS‑recognized compendia or acceptable peer‑reviewed medical literature is also not considered medically necessary and may be deemed not approvable and not reimbursable.

Prior Authorization and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior Authorization Required. Requests for Cresemba (isavuconazonium sulfate) require prior authorization. The treating clinician must document the member's diagnosis and demonstrate medical necessity consistent with the policy criteria; without adequate documentation the request cannot be properly reviewed.

Prior authorization required before benefit determination
Documentation must demonstrate diagnosis of Invasive Aspergillosis or Invasive Mucormycosis and meet medical necessity criteria

Documentation Required

Clinical Evidence Submission

Clinical evidence submission required. The treating physician or primary care provider must submit supporting clinical documentation and preauthorization materials (e.g., clinical notes, diagnostic test results, culture/histopathology reports, prior antifungal therapy history) to allow EmblemHealth to determine whether the member meets medical necessity criteria. EmblemHealth will not complete preauthorization or post-payment review without this information.

Submit pertinent clinical notes and diagnostic test results
Include microbiological culture/histopathology reports when available
Provide prior antifungal therapy history and rationale for Cresemba use

Note

Microbiological Documentation Recommended

Microbiological documentation. Specimens for fungal culture and relevant laboratory studies (including histopathology) should be obtained prior to initiating antifungal therapy when feasible. Therapy may start before results are available, but once available the treatment plan should be adjusted and results submitted with authorization requests.

Obtain and submit specimens for fungal culture and histopathology prior to therapy when feasible
If therapy begins empirically, submit culture/lab results as soon as available and document treatment adjustments

Step Therapy

No step therapy sequence specified. There is no step therapy or required trial sequence listed in this policy; coverage is contingent on meeting the documented diagnosis and medical necessity criteria outlined in the guideline.

No step therapy requirements specified in this policy
Coverage contingent on meeting policy clinical criteria

Denial Risk

Denial Risk / Not Medically Necessary Conditions

Not medically necessary / Denial risk conditions. Requests may be denied if selection criteria indicating lack of medical necessity are met (e.g., disease progression while on Cresemba, indications not supported by recognized compendia or peer-reviewed literature, contraindications such as known hypersensitivity, prohibited drug interactions, or familial short QT syndrome).

Denial risk if disease progression occurs while on Cresemba
Denial risk for indications not supported by CMS-recognized compendia or acceptable peer-reviewed literature
Contraindications and significant drug interactions must be documented and considered

Clinical Background

Isavuconazonium sulfate (Cresemba) is the prodrug of isavuconazole. As an azole antifungal, isavuconazole inhibits lanosterol 14‑alpha‑demethylase, impairing ergosterol synthesis in fungal cell membranes and thereby exerting antifungal activity against invasive molds such as Aspergillus and agents of mucormycosis.

Clinically relevant pharmacology includes significant interactions mediated by CYP3A4: coadministration with strong CYP3A4 inhibitors increases isavuconazole exposure, while coadministration with strong CYP3A4 inducers decreases exposure. Additionally, isavuconazole can shorten the QTc interval in a concentration‑related manner, which contraindicates its use in patients with familial short QT syndrome.

Policy Revision History

2025-03-13annual_reviewLatest

Annual review updated ICD-10 codes.

2024-11-15material_change

Restored coverage to the Medicaid population; updated title to include 'intravenous' and removed the '18 years and older' age limitation.

2023-01-01material_change

Removed coverage from the Medicaid population.

2022-04-08administrative

Policy transferred to new template.

2020-04-06initial_policy

New medical policy established per FDA label.

B44.0	Invasive pulmonary aspergillosis
B44.1	Other pulmonary aspergillosis
B44.2	Tonsillar aspergillosis
B44.7	Disseminated aspergillosis
B44.81	Allergic bronchopulmonary aspergillosis
B44.89	Other forms of aspergillosis
B44.9	Aspergillosis, unspecified
B46.0	Pulmonary mucormycosis
B46.1	Rhinocerebral mucormycosis
B46.2	Gastrointestinal mucormycosis

OpenPayer

Cresemba® (isavuconazonium sulfate) Intravenous

Coverage and Medical Necessity Criteria

Applicable Codes and Quantity Limits

Prior Authorization and Documentation Requirements

Clinical Background

Definitions and Drug Information

Policy Revision History