ModifiedCentenePolicy CP.PHAR.190

Ambrisentan (Letairis) — Coverage Criteria

Defines medical necessity and authorization criteria for ambrisentan (Letairis) use in members with pulmonary arterial hypertension (PAH) across Centene lines of business.

Policy Summary

PayerCentene

PolicyAmbrisentan (Letairis) — Coverage Criteria

Policy CodePolicy CP.PHAR.190

Change TypeMaterial: generic redirectionapproval duration revised

Effective Date03.16

Next Review Date

Key ActionSubmit prior authorization with documentation of PAH diagnosis, specialist involvement, prior therapy failure or contraindication, and justification if brand Letairis is requested instead of generic.

SourceLink

POLICY UPDATE CHANGES

Added generic redirection language requiring use of generic ambrisentan before brand Letairis unless contraindicated or adverse effects.

Revised approval duration for Commercial line of business to 12 months or duration of request, whichever is less.

Revised medical justification language to 'must use' language for generic redirection and added generic redirection to continued therapy.

Criteria also applies to brand Letairis.

Removed commercially unavailable branded products from Appendix B and updated dosing regimens per Clinical Pharmacology.

Clarified criteria also applies to brand Letairis. (P&T Approval Date = 02.25)

10 mg/daymaximum dose (PAH)

12 monthsCommercial approval

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6 monthsMedicaid/HIM initial

5 mg, 10 mgtablet strengths

1Q 2025most recent review

Coverage Criteria for Ambrisentan (Letairis)

Initial Therapy

Covered when ALL of the following are met:

Initial Approval: 1. Diagnosis of pulmonary arterial hypertension (PAH). 2. Prescribed by or in consultation with a cardiologist or pulmonologist. 3. Failure of a calcium channel blocker (see Appendix B), unless the member has a contraindication or experiences clinically significant adverse effects to calcium channel blockers. 4. Inadequate response to acute vasodilator testing or a contraindication to acute vasodilator testing. 5. Dose does not exceed 10 mg per day and does not exceed 1 tablet per day. 6. 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 6 months; Commercial 12 months or duration of request, whichever is less.

Continuation Therapy

Covered when ALL of the following are met:

Continued Therapy: 1. Member meets one of the following: a) currently receiving the medication via the Centene benefit; or b) member previously met initial approval criteria (or is enrolled in a state/product with continuity of care regulations where applicable). 2. Diagnosis of pulmonary arterial hypertension (PAH). 3. Member is responding positively to therapy. 4. If the request is for brand Letairis, the member must use generic ambrisentan unless contraindicated or clinically significant adverse effects are experienced. 5. For dose increases, the new dose does not exceed 10 mg per day and does not exceed 1 tablet per day.

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

Non‑FDA indications not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety in accordance with applicable off‑label use policies or evidence of coverage. Applicable off‑label policies include CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.

When state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, the state Medicaid coverage provisions take precedence. Providers should consult the applicable state Medicaid manual for any specific coverage requirements or differences before submitting an authorization request for a Medicaid member.

Use of ambrisentan in pregnancy is contraindicated due to embryo‑fetal toxicity; the drug is subject to pregnancy precautions and REMS requirements per the boxed warning. Requests for use in non‑FDA indications or during pregnancy will not be authorized unless documentation meets the referenced off‑label policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) and demonstrates adequate safety and efficacy.

Coding and Dosing Information

Policy identifiermixed

CP.PHAR.190

Clinical Policy reference number

inv-07: Maximum daily dose — key dosing limit for PAH.

Maximum daily dose (PAH)10 mg per day (maximum recommended dose)

Tablet strengths available5 mg, 10 mg

Dosing frequencyOne tablet once daily (QD)

Provider Actions, Authorization & Documentation

Prior Authorization

Prior Authorization & Documentation Requirements

Prior authorization is required. Requests must include documentation (e.g., office chart notes, lab results, prior medication records) that supports the diagnosis and that the member meets all approval criteria, including specialist involvement and any required trial or intolerance of calcium channel blockers per Appendix B. Failure to provide adequate documentation or requests for non‑FDA indications without required justification may result in denial.

Provider must submit supporting documentation such as office notes, labs, and medication history.
If requesting brand Letairis, documentation must show member used generic ambrisentan or had a contraindication/clinically significant adverse effect.
Documented failure of a calcium channel blocker (Appendix B) is required unless contraindicated or not tolerated.
Commercial approvals are generally for 12 months or duration of request (whichever is less); Medicaid/HIM durations differ—verify member's line of business.
State Medicaid coverage provisions take precedence over this policy when conflicts exist.

Background

Ambrisentan is a selective endothelin receptor antagonist indicated to improve exercise capacity and delay clinical worsening in pulmonary arterial hypertension (PAH, WHO Group 1). Clinical trials primarily enrolled patients with WHO functional class II–III; the agent may be used as part of combination therapy to reduce disease progression and hospitalization. The product carries a boxed warning for embryo‑fetal toxicity, making it contraindicated in pregnancy and subject to REMS/pregnancy precautions. For PAH dosing, tablets are available in multiple strengths with a maximum recommended dose of 10 mg per day.

Key Definitions and Safety Information

inv-17: PAH (Pulmonary Arterial Hypertension) — definition / WHO Group 1 context.

WHO classificationPulmonary arterial hypertension (PAH) = WHO Group 1

Clinical consequenceGroup 1 PAH is characterized by elevated pulmonary vascular resistance leading to right heart dysfunction and is the population targeted by endothelin receptor antagonists

Therapeutic contextLetairis (ambrisentan) is indicated to improve exercise ability and delay clinical worsening in PAH; may be used in combination with tadalafil

inv-18: REMS/Boxed warning — embryo‑fetal toxicity and pregnancy contraindication.

Boxed warningEmbryo-fetal toxicity — ambrisentan has a boxed warning for embryo-fetal toxicity

Contraindication

Policy Summary

PayerCentene

PolicyAmbrisentan (Letairis) — Coverage Criteria

Policy CodePolicy CP.PHAR.190

Change TypeMaterial: generic redirectionapproval duration revised

Effective Date03.16

Next Review Date

SourceLink

On This Page

Documentation Required

Documentation Expectations

Providers should document compliance with prior authorization criteria when submitting initial and continuation requests. Acceptable documentation includes but is not limited to: office/consultation notes from a cardiologist or pulmonologist, results of acute vasodilator testing, records showing trial and failure or intolerance of calcium channel blockers, medication administration records, and documentation of clinical response to therapy for continuation requests.

Specialist consultation or prescribing clinician note (cardiology or pulmonology) is expected.
Evidence of inadequate response to acute vasodilator testing where applicable.
Medication history showing trial and failure of calcium channel blockers (see Appendix B) or documentation of contraindication/adverse effects.
For continuation: documentation of positive clinical response and prior approval or continuity of care enrollment when applicable.

Step Therapy

Generic Redirection Requirement

Generic redirection is required: when generic ambrisentan is available, members must use the generic product for initial and continued therapy unless there is documented contraindication or clinically significant adverse effects to the generic.

Requests for brand Letairis must include documentation that generic ambrisentan was tried and failed or was contraindicated/caused clinically significant adverse effects.
Generic redirection applies to initial approvals and continuation of therapy.

Denial Risk

Documentation/Indication Risk

Documentation/Indication Risk — Missing or incomplete documentation, lack of required specialist consultation, absence of evidence for trial/failure of calcium channel blockers, or requests for non‑FDA indications without supporting justification increase risk of denial. Providers should ensure all required clinical information is included at time of submission to avoid delays.

Non‑FDA uses require submission of evidence per off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) as applicable to line of business.
When state Medicaid rules conflict with this policy, state rules prevail.

Use in pregnancy is contraindicated

REMS requirementPregnancy precautions/REMS program required per boxed warning

inv-19: Generic redirection — policy language requiring use of generic when available, applied to initial and continued therapy.

Generic redirection requirementMust use generic ambrisentan before brand Letairis unless contraindicated or clinically significant adverse effects are experienced

Scope of applicationGeneric redirection language was added to both initial and continued therapy sections and applies to requests for brand Letairis

Provider documentationWhen requesting brand, provider should document contraindication or adverse effects to generic formulation