ModifiedmhnPolicy CP.PHAR.190

Ambrisentan (Letairis) for pulmonary arterial hypertension

This policy governs prior authorization, coverage criteria, dosing limits, and contraindications for ambrisentan (Letairis) in members with pulmonary arterial hypertension (PAH) across commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyAmbrisentan (Letairis) for pulmonary arterial hypertension

Policy CodePolicy CP.PHAR.190

Change TypeCriteria clarification, quantity-limit requirement, approval-duration revisions

Effective DateMar 16, 2023

Next Review DateFeb 26, 2025

Key ActionSubmit prior authorization with documentation of PAH diagnosis, specialist involvement, prior calcium channel blocker failure when applicable, and ensure requested quantity and dose do not exceed plan limits.

SourceLink

POLICY UPDATE CHANGES

Clarified criteria also applies to brand Letairis.

Added requirement that request does not exceed health-plan approved quantity limit.

Extended Medicaid and HIM initial approval duration from 6 months to 12 months for this maintenance medication for a chronic condition.

Removed commercially unavailable branded products from Appendix B.

10 mg/daymaximum approved daily dose

5 mgusual starting dose for PAH

12 monthstypical approval duration

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Coverage Criteria for Ambrisentan (Letairis)

Initial Therapy (PAH)

Covered when ALL of the following are met:

Initial PAH Approval: 1) Diagnosis of pulmonary arterial hypertension (PAH, WHO Group 1); 2) Prescribed by or in consultation with a cardiologist or pulmonologist; 3) Failure of a calcium channel blocker (see Appendix B) unless either: a) inadequate response to acute vasodilator testing, or b) contraindication or clinically significant adverse effects to calcium channel blockers; 4) If request is for brand Letairis, member must use generic ambrisentan unless contraindicated or clinically significant adverse effects are experienced; 5) Request does not exceed the health-plan approved quantity limit; 6) Dose does not exceed both: a) 10 mg per day, and b) 1 tablet per day.dose <= 10 mg/day and tablets <= 1/day

Approval duration: Medicaid/HIM - 12 months; Commercial - 12 months or duration of request, whichever is less

Continuation Therapy (PAH)

Covered when ALL of the following are met:

Continuation PAH Approval: 1) Member is currently receiving medication via the health plan benefit or has previously met initial approval criteria, OR member is receiving medication and is enrolled in a state/product with continuity-of-care regulations; 2) Member is responding positively to therapy; 3) If request is for brand Letairis, member must use generic ambrisentan unless contraindicated or clinically significant adverse effects are experienced; 4) Request does not exceed the health-plan approved quantity limit; 5) If a dose increase is requested, the new dose does not exceed both: a) 10 mg per day, and b) 1 tablet per day.dose <= 10 mg/day and tablets <= 1/day

Approval duration: Medicaid/HIM - 12 months; Commercial - 12 months or duration of request, whichever is less

Other/Off-Label Uses

If use is not addressed in primary criteria:

Other Indications: 1) If the drug has had a label change within the last 6 months that is not yet reflected in this policy (e.g., new indication, age expansion, dosing), follow the applicable formulary/no-coverage or non-formulary policy for the relevant line of business per the options listed in the policy; OR 2) If the requested use (diagnosis, age, dosing) is not specifically listed under the 'Diagnoses/Indications for which coverage is NOT authorized' section and criterion 1 does not apply, refer to the off-label use policy for the appropriate line of business (CP.CPA.09, HIM.PA.154, or CP.PMN.53).

Updated Coverage Criteria Notes

Policy criteria updates and applicability notes

Brand applicability: Criteria clarified to also apply to brand Letairis in addition to generic ambrisentan.

Applies equally to brand and generic ambrisentan.

Quantity limit: Requests must not exceed the health-plan approved quantity limit.

New requirement added in 1Q 2026 annual review.

Approval duration revisions: Medicaid and HIM initial approval duration extended from 6 months to 12 months for maintenance therapy; Commercial approval duration revised to 12 months or duration of request, whichever is less.

Duration revisions per 1Q 2026 and prior reviews.

Requests for uses that are not FDA-approved and are not specifically addressed in this policy will not be authorized unless the provider supplies sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policy for the member's line of business (see CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or other applicable evidence of coverage documents.

Providers should be prepared to submit clinical records (e.g., office notes, diagnostic testing, and literature or other evidence) that justify the requested off‑label use and meet the standards defined in the referenced off‑label use policies; absent such documentation, the request may be denied.

Ambrisentan has specific safety limitations that affect coverage. Contraindications include pregnancy and idiopathic pulmonary fibrosis. The drug carries a boxed warning for embryo‑fetal toxicity, and prescribers and patients must follow the associated REMS program requirements.

Because of these risks, documentation demonstrating absence of pregnancy and adherence to REMS safeguards may be required as part of any authorization request.

When there is a conflict between this clinical policy and a state's Medicaid coverage provisions, state Medicaid coverage provisions take precedence. Providers and reviewers must follow the applicable state Medicaid manual and related guidance for any Medicaid members.

The portion of the document provided does not list any conditions that are explicitly designated as not medically necessary. This clinical policy is intended as a guide to medical necessity and coverage decision‑making, and final coverage determinations remain subject to benefit terms, exclusions, limitations, and applicable state and federal requirements.

Coding and Dosing Limits

No codes listed in this document portionmixed

No codes listed

Maximum daily dose — key thresholds

Maximum daily dose10 mg per day

Typical starting dose for PAH5 mg PO once daily

Tablet strengths available5 mg, 10 mg

Health-plan quantity limit

Health-plan quantity limit requirementRequest must not exceed the health-plan approved quantity limit

Potential denial for exceedanceRequests that exceed the health-plan approved quantity limit may be denied

Policy effective change

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests for ambrisentan (including brand Letairis) must include documentation of a pulmonary arterial hypertension (PAH) diagnosis and that the drug is prescribed by or in consultation with a cardiologist or pulmonologist. For initial therapy, documentation that the member failed a calcium channel blocker is required unless the member has inadequate response/contraindication to acute vasodilator testing or contraindication/clinically significant adverse effects to calcium channel blockers. If the request is for brand Letairis, the member must use generic ambrisentan unless contraindicated or clinically significant adverse effects are experienced. Approval duration: Medicaid/HIM — 12 months; Commercial — 12 months or duration of request, whichever is less.

Applies to brand Letairis and generic ambrisentan
Approval duration: Medicaid/HIM = 12 months; Commercial = 12 months or duration of request, whichever is less
Prior authorization must demonstrate specialist prescribing or consult

Documentation Required

Required Documentation

Background

Ambrisentan (brand Letairis) is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group 1) to improve exercise capacity and delay clinical worsening in adults. Clinical studies primarily involved patients with WHO functional class II–III and included idiopathic/heritable and connective tissue disease–associated PAH.

Typical dosing for PAH begins at 5 mg orally once daily, with a maximum recommended dose of 10 mg per day. Tablets are available in strengths corresponding to these dosing options, and dosing must remain within the policy's maximum daily dose and tablet limits.

Definitions and Terms

PAH (WHO Group 1) — definition

DefinitionPulmonary arterial hypertension (PAH) is pulmonary hypertension classified as World Health Organization (WHO) Group 1

Clinical featuresCharacterized by elevated pulmonary arterial pressure due to vascular remodeling; studies mainly included WHO FC II–III patients

Indication contextAmbrisentan is indicated to improve exercise ability and delay clinical worsening in adult patients with WHO Group 1 PAH

Letairis — brand definition and applicability

Letairis — brand nameLetairis is the brand name for ambrisentan

Criteria applicabilityPolicy/criteria clarified to apply to the brand Letairis in addition to generic ambrisentan