CurrentmhnPolicy CP.PMN.275

Clinical Policy: Levoketoconazole (Recorlev)

Defines medical necessity criteria, initial and continuation authorization requirements, dosing limits, contraindications, and step-therapy expectations for levoketoconazole (Recorlev) for treatment of endogenous Cushing's syndrome in adults across Commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyClinical Policy: Levoketoconazole (Recorlev)

Policy CodePolicy CP.PMN.275

Change TypeClarified (step therapy bypass for IL HIM); annual reference updates

Effective DateJun 1, 2022

Next Review Date

Key ActionProvider must submit chart notes, lab results or other clinical information supporting member meets approval criteria.

POLICY UPDATE CHANGES

Added step therapy bypass for IL HIM per IL HB 5395.

2Q 2025 annual review: no significant changes; references reviewed and updated.

2Q 2024 annual review: no significant changes; references reviewed and updated.

Policy created.

1Covered Indication(s)

1,200 mg/dayMaximum Dose

≥18Minimum Age (years)

6 moInitial Approval Duration

Coverage Summary

Scope: This policy defines medical necessity criteria, initial and continuation authorization requirements, dosing limits and exclusions for levoketoconazole (Recorlev) for treatment of endogenous Cushing's syndrome in adults. Coverage stance: Covered with criteria when used for adults (≥ 18 years) with endogenous Cushing's syndrome for whom surgery is not an option or has not been curative, prescribed by or in consultation with an endocrinologist, with prior failure of ketoconazole unless contraindicated or not tolerated, and with dose not to exceed 1,200 mg/day. Ketoconazole is listed as a therapeutic alternative (off-label) and is recommended as a second-line steroidogenesis inhibitor in relevant guidelines.

Initial Therapy Criteria (Cushing's Syndrome)

Continuation Therapy Criteria

Unapproved Uses / Exclusions

III. Diagnoses/Indications NOT authorized

Coverage is NOT authorized for:

Non‑FDA approved indications that are not addressed in this policy are not authorized unless there is sufficient documentation of efficacy and safety per the off-label use policies or evidence of coverage documents (see policy body for references)

Levoketoconazole is not approved for treatment of fungal infections. Ketoconazole is listed in the policy as a therapeutic alternative and its use for Cushing's syndrome is considered off-label and recommended as a second-line steroidogenesis inhibitor in guideline guidance.

Provider Actions / Prior Authorization Requirements

Documentation Required

Submit supporting documentation

Provider must submit office chart notes, laboratory results, or other clinical information supporting that the member meets approval criteria. Documentation should support the diagnosis of Cushing's syndrome, prior therapy failure (or contraindication), surgical status (surgery not curative or member not eligible), specialist consultation, and labs showing response when requested for continuation.

Prior Authorization

Specialist involvement requirement

For initial approval, the prescription must be written by or in consultation with an endocrinologist.

Applicable Codes / Policy Cross-references

Referenced Policy Identifiers / Cross-referencesmixed

CP.CPA.190	Commercial no coverage criteria policy (referenced for label change scenarios)
HIM.PA.33	Health insurance marketplace no coverage criteria policy (referenced for label change scenarios)
CP.PMN.255	Medicaid no coverage criteria policy (referenced for label change scenarios)
HIM.PA.103	Health insurance marketplace non-formulary policy (referenced)
CP.PMN.16	Medicaid non-formulary policy (referenced)
CP.CPA.09	Commercial off-label use policy (referenced)
HIM.PA.154	Health insurance marketplace off-label use policy (referenced)
CP.PMN.53	Medicaid off-label use policy (referenced)
CC.PHARM.03A	State addendum for continuity of care (referenced)
CC.PHARM.03B	State addendum for continuity of care (referenced)

Clinical Evidence & Guidelines

Evidence sources referenced in the policy include the FDA prescribing information for Recorlev (Recorlev Prescribing Information; Xerix Pharmaceuticals; June 2023), clinical trial data such as the SONICS phase 3 study (Pivonello et al. 2021), and guideline support from the 2015 Endocrine Society Clinical Practice Guideline and the 2021 Pituitary Society guideline update.

Background

Background: Levoketoconazole (Recorlev) is a cortisol synthesis inhibitor indicated by the FDA for treatment of endogenous hypercortisolemia in adult patients with Cushing's syndrome when surgery is not an option or has not been curative. The product is not approved for fungal infections. Ketoconazole is included in the policy appendix as a therapeutic alternative and its use for Cushing's syndrome is considered off-label and endorsed as a second-line steroidogenesis inhibitor by relevant guidelines.

Revision History

2026-01-01policy_changeLatest

Step therapy bypass for Illinois HIM per IL HB 5395 (step therapy requirements do not apply for Illinois HIM requests) — MATERIAL

2025-02-03annual_review

2Q 2025 annual review: no significant changes; references reviewed and updated

2024-02-08annual_review

2Q 2024 annual review: no significant changes; references reviewed and updated