ModifiedmhnPolicy CP.PHAR.208

Sodium Phenylbutyrate (Buphenyl, Pheburane, Olpruva)

This policy defines medical necessity criteria, dosing limits, and prior authorization requirements for sodium phenylbutyrate products used as adjunctive therapy for urea cycle disorders for affected lines of business.

Policy Summary

Payermhn

PolicySodium Phenylbutyrate (Buphenyl, Pheburane, Olpruva)

Policy CodePolicy CP.PHAR.208

Change TypeMaterial updates (age extension, dietary requirement, approval duration, generic redirection)

Effective Date05.01.16

Next Review Date

Key ActionSubmit prior authorization with documentation confirming UCD diagnosis, dietary protein restriction, and that dosing does not exceed 20 g/day.

SourceLink

POLICY UPDATE CHANGES

Added pediatric age extension to 1 year old for Olpruva.

Added requirement for dietary protein restriction per labeling as a condition of coverage.

Extended initial approval duration from 6 to 12 months.

Redirected to generic sodium phenylbutyrate for use unless contraindicated or adverse events occur.

20 g/daymax daily dose

≥1 yrOlpruva min age

≥7 kgOlpruva min weight

12 moapproval duration

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Coverage Criteria

Initial Therapy

Covered when ALL of the following are met:

UCD initial approval: 1) Diagnosis of a urea cycle disorder caused by CPS, OTC, or AS deficiency confirmed by enzymatic, biochemical, or genetic analysis; 2) Prescribed by or in consultation with a physician experienced in treating metabolic disorders; 3) If request is for Olpruva, member meets both: weight ≥ 7 kg AND age ≥ 1 year; 4) Member must use generic sodium phenylbutyrate tablets or powder unless contraindicated or clinically significant adverse events occur; 5) Member must currently be on dietary protein restriction; 6) Dose does not exceed 20 grams per day.see node text

Approval duration: 12 months

Continuation Therapy

Continued coverage when ALL of the following are met:

UCD continued approval: 1) Member is currently receiving medication via the Centene benefit or has previously met initial approval criteria, or member is receiving medication with continuity of care protections; 2) If request is for Olpruva, member meets both: weight ≥ 7 kg AND age ≥ 1 year; 3) Member must use generic sodium phenylbutyrate tablets or powder unless contraindicated or clinically significant adverse events occur; 4) Member is responding positively to therapy; 5) Member must currently be on dietary protein restriction; 6) If request is for a dose increase, the new dose does not exceed 20 grams per day.see node text

Approval duration: 12 months

Other Indications

For other indications:

Other uses: 1) If the drug has recently (within the last 6 months) undergone a label change not yet reflected in this policy (for formulary or non‑formulary status follow the specified policies); OR 2) If the requested use (diagnosis, age, dosing) is not listed under Section III and criterion 1 does not apply, refer to the off‑label use policy for the relevant line of business (CP.CPA.09, HIM.PA.154, or CP.PMN.53).

See referenced policies for procedural steps

Requests for non–FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policy (see CP.CPA.09 for commercial, HIM.PA.154 for marketplace, and CP.PMN.53 for Medicaid) or other evidence of coverage documents.

No additional exclusions or special coverage caveats are specified in the source chunks provided for this section.

Sodium phenylbutyrate products are not indicated for management of acute hyperammonemia; use in that setting is contraindicated and inappropriate because acute hyperammonemia is a medical emergency requiring different acute management.

No additional contraindications or 'not medically necessary' statements are specified in the provided chunks beyond those already stated elsewhere in the policy.

Initial Therapy

Initial authorization requires all criteria be met:

Initial: Diagnosis of a urea cycle disorder (CPS, OTC, or AS) confirmed by enzymatic, biochemical, or genetic analysis; prescribed by or in consultation with a physician experienced in metabolic disorders; if Olpruva requested, member ≥ 7 kg and ≥ 1 year; generic sodium phenylbutyrate tablets or powder preferred unless contraindicated or clinically significant adverse events occur; member must be on dietary protein restriction; dose ≤ 20 g/day.

Approval duration: 12 months

Initial therapy

Initial therapy — Parameters updated in 1Q 2026 review:

initial_approval_duration: Initial approval duration extended from 6 to 12 months.12 months

Continuation Therapy

Continued therapy is authorized when all continuation criteria are met:

Continuation: Member currently receiving medication via benefit or previously met initial criteria (or has continuity of care protections); if Olpruva requested, member ≥ 7 kg and ≥ 1 year; member must use generic sodium phenylbutyrate tablets or powder unless contraindicated or clinically significant adverse events occur; member is responding positively to therapy; member must be on dietary protein restriction; if dose increase requested, new dose ≤ 20 g/day.

Approval duration: 12 months

Continued approval

Continued approval — Considerations referenced in policy updates:

generic redirection: Redirection to generic sodium phenylbutyrate was added to the continued approval section per August SDC; this may function as a preference/step to generic products.

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit supporting documentation (e.g., office chart notes, laboratory results, genetic or enzymatic testing, dosing information) that demonstrates the member meets all approval criteria for sodium phenylbutyrate (Buphenyl, Pheburane, Olpruva). Requests for Olpruva must document applicable age and weight criteria. Requests for non‑FDA (off‑label) indications will not be authorized unless sufficient documentation of efficacy and safety is provided per the applicable off‑label use policies (CP.CPA.09 for Commercial, HIM.PA.154 for HIM, CP.PMN.53 for Medicaid) or evidence of coverage documents.

Provider must submit office chart notes, labs, genetic or enzymatic testing results, and other clinical documentation to support the request.
If requesting Olpruva, document weight ≥ 7 kg and age ≥ 1 year.
Requests for non‑FDA indications require supporting evidence per off‑label policies (CP.CPA.09, HIM.PA.154, CP.PMN.53).
Generic-preferred: member must use generic sodium phenylbutyrate tablets or powder unless contraindicated or significant adverse events occur.
Provider must document that member is on dietary protein restriction as required by labeling.

Step Therapy / Product Preference

Step	Requirement	Notes
1	Preference for generic sodium phenylbutyrate tablets or powder; brand products (e.g., Buphenyl, Pheburane, Olpruva) are allowed only if the generic formulation is contraindicated or the member experiences clinically significant adverse events with the generic.	Per policy directive added via August SDC; generic redirection affirmed in 1Q reviews.

Context	Policy language	Implementation
Initial approval	• Member must use generic sodium phenylbutyrate tablets or powder, unless contraindicated or clinically significant adverse events are experienced; • Approval duration: 12 months.	Generic redirection was added to initial approval criteria (August SDC) and reflected in subsequent annual reviews; apply generic preference when processing initial prior authorizations.
Continued approval	Member must use generic sodium phenylbutyrate tablets or powder, unless contraindicated or clinically significant adverse events are experienced; member must be responding to therapy; approval duration: 12 months.	Continued approval section was updated to redirect to generic product per August SDC; enforce generic preference for renewals unless documented contraindication or adverse event exists.

Coding & Dosing Limits

inv-08: Maximum daily dose — 20 grams/day

Maximum daily dose20 grams/day

Applies toAll sodium phenylbutyrate products (Buphenyl, Pheburane, Olpruva)

Reference dosing guidanceSee weight-based regimens in Dosage & Administration; maximum cap remains 20 g/day

inv-09: Dosing frequency — three to six equally divided doses per day

Recommended dosing frequencyThree to six equally divided doses per day (with each meal or feeding)

Weight-based contextApplies across weight-based regimens for sodium phenylbutyrate formulations

Administration timing

Quantity Limits

inv-27: Sodium phenylbutyrate (all products) — quantity limit entry (20 grams)

Quantity limit entry20 grams per day

Unitgrams/day

Applies toAll sodium phenylbutyrate products

Definitions

inv-19: Urea cycle disorders (UCDs) definition — enzymes and examples (CPS1, OTC, AS, ASL, NAGS, arginase)

DefinitionUrea cycle disorders (UCDs) are caused by deficiencies of enzymes in the urea cycle that transform nitrogen to urea

Key enzymes (examples)Carbamoyl phosphate synthetase 1 (CPS1), Ornithine transcarbamylase (OTC), Argininosuccinate synthetase (AS), Argininosuccinate lyase (ASL), N-acetyl glutamate synthetase (NAGS), Arginase

Clinical consequenceEnzyme deficiencies disrupt nitrogen elimination and can lead to hyperammonemia

inv-20: Carbamoyl phosphate synthetase 1 — enzyme name clarified from 'CPSI' to 'CPS1'

Clarified enzyme nameCPS1 (Carbamoyl phosphate synthetase 1) — updated from 'CPSI' to 'CPS1' in policy appendix

Source of update

Background

Urea cycle disorders (UCDs) are inherited enzyme deficiencies that impair conversion of nitrogen to urea, resulting in hyperammonemia. Sodium phenylbutyrate is an ammonia‑scavenging, nitrogen‑binding agent used as adjunctive chronic therapy for UCDs (including deficiencies of CPS1, OTC, and AS) together with dietary protein restriction; it is not intended for acute hyperammonemia management. Recent policy updates (1Q 2026) clarify pediatric dosing parameters for Olpruva and add dietary protein restriction as a required element of authorization.

Revision History

2026-02-26P&T approval / annual reviewLatest

1Q 2026 annual review: added pediatric age extension to 1 year for Olpruva, added requirement for dietary protein restriction per labeling, and extended initial approval duration from 6 to 12 months.

2025-02-25P&T approval / annual review

1Q 2025 annual review: no significant clinical changes; references reviewed and updated.

2024-02-24