CurrentmhnPolicy CP.PHAR.196

UPTRAVI (PDF)

Clinical policy governing medical necessity criteria, initial and continuation approval requirements, dosing limits, formulation-specific rules, contraindications, appendix therapeutic alternatives, and approval durations for Uptravi (selexipag) across Commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyUPTRAVI (PDF)

Policy CodePolicy CP.PHAR.196

Change TypeRevised (1Q 2026, 1Q 2024, prior revisions)

Effective Date2003-16

Next Review Date

Key ActionProvider must submit documentation supporting that member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

1Q 2026 annual review clarified maximum dose for concomitant administration with CYP2C8 inducers; clarified requirement for titration plan is for oral Uptravi; 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.

1Q 2024 annual review added IV Uptravi 1800 mcg/10 mL formulation and criteria for use per prescribing information.

Revised approval duration for Commercial line of business to 12 months or duration of request, whichever is less (prior: length of benefit).

1Covered Indication (FDA-approved)

2Formulations covered (oral, IV)

3200/3600Std max daily doses (oral/IV mcg)

Max doses w/ CYP2C8 inducer (oral/IV mcg)

12mApproval duration (Medicaid/HIM/Commercial)

Coverage Summary

Overview: Selexipag (Uptravi) is a prostacyclin receptor (IP) agonist indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group 1) to delay disease progression and reduce the risk of hospitalization. Effectiveness was established in long-term PAH studies in patients predominantly with WHO Functional Class II-III symptoms. Coverage stance: covered_with_criteria. Status: CURRENT.

Key thresholds, approval duration, and formulations

Approval duration (Medicaid/HIM)12 months

Approval duration (Commercial)12 months or duration of request, whichever is less

Formulations coveredOral tablets and IV single‑dose vial (1800 mcg/10 mL)

Standard maximum oral daily dose3,200 mcg/day

Standard maximum IV daily dose3,600 mcg/day

Max oral daily dose with CYP2C8 inducer (e.g., rifampin)Up to 6,400 mcg/day

Max IV daily dose with CYP2C8 inducer (e.g., rifampin)Up to 7,200 mcg/day

Medical Necessity Criteria

I. Initial Approval Criteria - Pulmonary Arterial Hypertension

Covered when ALL of the following are met:

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II. Continued Therapy / Maintenance - Pulmonary Arterial Hypertension

Covered when ALL of the following are met:

ALL of the following

Pulmonary Arterial Hypertension (must meet all)
- Member status (ONE of):
  - Currently receiving medication via Centene benefit or member has previously met initial approval criteria.

Provider Actions / Prior Authorization

Documentation Required

Supporting clinical documentation required

Provider must submit documentation (office chart notes, lab results, or other clinical information) supporting that the member meets all approval criteria. See policy for specifics on diagnosis, prior therapies, formulation, dosing limits, and titration plan requirements.

Prior Authorization

Prescriber specialty requirement

Prescription must be written by a cardiologist or pulmonologist, or written in consultation with one (i.e., prescriber specialty requirement for approval).

Policy Identifiers and References

Policy identifiers / Reference numbersmixed

CP.PHAR.196	Clinical Policy Reference Number for Selexipag (Uptravi)
CP.CPA.09	Off-label use policy (commercial) referenced
HIM.PA.154	Off-label use policy (marketplace) referenced
CP.PMN.53	Off-label use policy (Medicaid) referenced
CC.PHARM.03A	State-specific continuity of care addendum A
CC.PHARM.03B	State-specific continuity of care addendum B

Key references and evidence:

• FDA approved indication: Treatment of PAH (WHO Group 1) to delay disease progression and reduce risk of hospitalization (Uptravi Prescribing Information).

• Key references: Uptravi Prescribing Information (July 2022) and guideline references (ESC/ERS, CHEST, AHA/ATS) as listed in the policy references.

Definitions:

• PAH: Pulmonary arterial hypertension (WHO Group 1).

• CYP2C8 inducer: Drugs that induce CYP2C8 (example provided in policy: rifampin), which may require higher Uptravi dosing limits.

Background / Clinical Context

Background: Selexipag (Uptravi) is a non-prostanoid prostacyclin (IP) receptor agonist that targets the prostacyclin pathway to reduce pulmonary arterial pressure via vasodilation. It is indicated to delay disease progression and reduce hospitalization risk in WHO Group 1 PAH. Effectiveness was demonstrated in a long-term study in PAH patients, primarily those with WHO Functional Class II-III symptoms. Dosing and administration include titration of oral tablets up to a maximum of 3,200 mcg/day (tablets) and 3,600 mcg/day (injection), with higher maximums when coadministered with a CYP2C8 inducer (e.g., rifampin) as specified in the policy.

Revision History

2026-02-26revisedLatest

2024-02-24added

1Q 2024 annual review added IV Uptravi 1800 mcg/10 mL formulation and criteria for use per prescribing information.

2022-11-22revised

Policy Summary

Payermhn

PolicyUPTRAVI (PDF)

Policy CodePolicy CP.PHAR.196

Change TypeRevised (1Q 2026, 1Q 2024, prior revisions)

Effective Date2003-16

Next Review Date

Key ActionProvider must submit documentation supporting that member meets all approval criteria.

SourceLink

On This Page

Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state addendums CC.PHARM.03A and CC.PHARM.03B).

Member is responding positively to therapy.

If request is for intravenous Uptravi, member is temporarily unable to take oral therapy.

If request is for a dose increase (ONE of):

Oral formulation dose increase (must meet ALL):
- New dose does not exceed one of the following:
  - 3,200 mcg per day.
  - 6,400 mcg per day if prescribed concomitantly with a CYP2C8 inducer (e.g., rifampin).
- If member requires titration, provider must submit a titration plan.
- Request does not exceed health-plan approved quantity limit.
IV formulation dose increase (must meet ALL):
- New dose does not exceed 3,600 mcg per day.
- New dose does not exceed 7,200 mcg per day if prescribed concomitantly with a CYP2C8 inducer (e.g., rifampin).

III. Other Diagnoses/Indications

Covered only when ONE of the following applies:

ANY of the following

If drug label changed within last 6 months and policy not yet updated, follow formulary/no-coverage or non-formulary policies as referenced (see policy body for specific policy numbers by line of business).
If requested use is not listed under section III (not-authorized list) and criterion above does not apply, refer to off-label use policy for the relevant line of business per referenced policy numbers (CP.CPA.09 commercial, HIM.PA.154 marketplace, CP.PMN.53 Medicaid).

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IV. Diagnoses/Indications Not Authorized

Not covered when the following applies:

ALL of the following

Non-FDA approved indications not addressed in this policy, unless sufficient documentation of efficacy and safety is provided per off-label use policies CP.CPA.09 (commercial), HIM.PA.154 (marketplace), and CP.PMN.53 (Medicaid) or evidence of coverage documents.

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Prior Authorization

Titration plan requirement

For oral Uptravi, if the member requires titration (initial therapy or dose increase), the provider must submit a titration plan with the request.

Billing Rule

Quantity limit adherence

Requests must not exceed the health-plan approved quantity limit; ensure the submitted quantity/duration complies with the plan’s approved limits.

Documentation Required

Failure of calcium channel blocker or exception

Provider must document failure of a calcium channel blocker per Appendix B, unless the member has inadequate response or a contraindication to acute vasodilator testing, or has a contraindication or clinically significant adverse effects to calcium channel blockers.

Prior Authorization

Formulation-specific oral/IV criteria

For IV Uptravi requests, document that the member is temporarily unable to take oral therapy. Also ensure IV dosing limits in the policy are not exceeded (maximums with and without concomitant CYP2C8 inducers apply).

Revised approval duration for Commercial line of business to 12 months or duration of request, whichever is less (prior: length of benefit).