ModifiedHealth NetPolicy N/A

Clinical Policy: Glycerol Phenylbutyrate (Ravicti)

Policy governs medical necessity criteria, prior authorization, and continuation requirements for glycerol phenylbutyrate (Ravicti) for treatment of urea cycle disorders across Health Net lines of business (Commercial, HIM, Medicaid). It specifies diagnostic confirmation, prescriber experience, stepwise redirection to alternatives, dosing limits, and approval durations.

Policy Summary

PayerHealth Net

PolicyGlycerol Phenylbutyrate (Ravicti) — Clinical Policy

Policy CodePolicy N/A

Change TypeMaterial revision — approval duration and stepwise redirection added

Effective Date05.01.16

Next Review DateN/A

Key ActionObtain prior authorization with diagnostic confirmation of UCD and documentation that stepwise redirection to generic sodium phenylbutyrate (then Pheburane if needed) and dose limits (≤17.5 mL/day) are met.

SourceLink

POLICY UPDATE CHANGES

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

Added stepwise redirection requiring use of generic sodium phenylbutyrate first, then Pheburane if intolerance or contraindication, for continuation of therapy and requests.

17.5 mL/dayMaximum Ravicti daily dose

12 monthsCommercial approval

6–12 monthsMedicaid/HIM approval

UCD

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Coverage Criteria for Ravicti (glycerol phenylbutyrate)

inv-01: Initial Therapy

Covered when ALL of the following are met:

Initial Approval for Ravicti: 1) Diagnosis of a UCD caused by one or more of the following, confirmed by enzymatic, biochemical, or genetic analysis: Carbamyl phosphate synthetase 1 (CPS1) deficiency; Ornithine transcarbamylase (OTC) deficiency; Argininosuccinate synthetase (AS) deficiency (classic citrullinemia, type I); Argininosuccinate lyase (ASL) deficiency (argininosuccinic aciduria); or Arginase deficiency.

Prescriber requirement: 2) Prescribed by or in consultation with a physician experienced in treating metabolic disorders.

Stepwise redirection for CPS1/OTC/AS: 3) For UCD caused by CPS1, OTC, or AS deficiency, BOTH: a) Member must use generic sodium phenylbutyrate unless contraindicated or clinically significant adverse events are experienced; and b) If member has intolerance or contraindication to generic sodium phenylbutyrate, member must use Pheburane unless contraindicated or clinically significant adverse effects occur.

Dose limitation: 4) Total daily dose does not exceed 17.5 mL (19 g) per day.<= 17.5 mL/day

inv-02: Continuation Therapy

Covered for continuation when ALL of the following are met:

Eligibility for continuation: 1) Member is currently receiving Ravicti via the benefit or has previously met initial approval criteria.

Stepwise redirection for CPS1/OTC/AS: 2) For UCD caused by CPS1, OTC, or AS deficiency, BOTH: a) Member must use generic sodium phenylbutyrate unless contraindicated or clinically significant adverse events are experienced; and b) If member has intolerance or contraindication to generic sodium phenylbutyrate, member must use Pheburane unless contraindicated or clinically significant adverse effects occur.

Clinical response: 3) Member is responding positively to therapy.

Dose limitation for increases: 4) If the request is for a dose increase, the new total daily dose does not exceed 17.5 mL (19 g) per day.<= 17.5 mL/day

Ravicti (glycerol phenylbutyrate) is indicated for the chronic management of urea cycle disorders (UCDs) but has specific limitations. The medication's safety and efficacy have not been established for N‑acetylglutamate synthase (NAGS) deficiency, and therefore use for NAGS deficiency is not supported by this policy. Additionally, Ravicti is not indicated for the treatment of acute hyperammonemia because acute episodes require more rapidly acting interventions to reduce plasma ammonia levels.

Requests for uses that are non‑FDA approved and not addressed in this policy will be denied unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies (e.g., CP.CPA.09 for Commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or evidence of coverage documents.

Coverage determinations described in this clinical policy are intended to assist in adjudicating benefits but are subject to the member's plan terms. All approvals, denials, and administration of benefits remain conditional on the Health Plan's applicable terms, conditions, exclusions, and limitations (for example, evidence of coverage, certificate of coverage, policy, or contract of insurance), as well as state and federal requirements and Health Plan administrative policies.

This clinical policy does not constitute medical advice or a guarantee of payment. Providers are expected to exercise independent clinical judgment in treating members and are responsible for medical decisions and documentation supporting requested services.

Explicit non‑coverage under this chronic management policy includes requests to treat acute hyperammonemia with Ravicti — such use is not authorized because more rapidly acting therapies are required. The policy also states that Ravicti's use for NAGS deficiency is not supported due to lack of established safety and efficacy and therefore is excluded from coverage.

In addition, non‑FDA indications that are not specifically addressed by this policy will be denied unless sufficient supporting documentation is provided per the applicable off‑label use policies or evidence of coverage provisions.

Dosage and Coding Information

inv-06: Maximum daily dose

Maximum daily dose17.5 mL/day (maximum total daily Ravicti dose)

Equivalent massApproximately 19 g/day (per policy statistics)

Dosing schedule noteTotal daily dosage given in 3 equally divided doses; round to nearest 0.5 mL (age ≥2 years) or 0.1 mL (age <2 years)

Prior Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization required. Provider must confirm the diagnosis of a urea cycle disorder (UCD) with enzymatic, biochemical, or genetic analysis and document specialist prescribing or consultation (physician experienced in metabolic disorders). Submit chart notes, lab results, or other clinical information supporting that the member meets ALL approval criteria.

Confirm UCD diagnosis by enzymatic, biochemical, or genetic testing.
Prescribed by or in consultation with a physician experienced in treating metabolic disorders.
Include chart notes and relevant lab results with the prior authorization request.

Step Therapy

Step Therapy / Redirection Required

Stepwise redirection to alternatives is required. For initial and continued therapy requests for members with UCD caused by CPS1, OTC, or AS deficiencies, require trial of generic sodium phenylbutyrate first. If the member has intolerance or a contraindication to generic sodium phenylbutyrate, the member must use Pheburane unless Pheburane is contraindicated or causes clinically significant adverse effects. Dose limits apply (does not exceed 17.5 mL [19 g] per day).

Background on Urea Cycle Disorders and Ravicti

Urea cycle disorders (UCDs) are inherited enzyme deficiencies that impair the conversion of nitrogen to urea, resulting in accumulation of ammonia and risk of hyperammonemia. Common enzyme defects include carbamyl phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase, and N‑acetylglutamate synthase (NAGS).

Ravicti (glycerol phenylbutyrate) is a nitrogen‑binding agent approved for the chronic management of UCDs in patients who cannot be managed by dietary protein restriction and amino acid supplementation alone. It is intended to be used with dietary protein restriction and, when appropriate, essential amino acids or arginine/citrulline supplementation. Ravicti is not indicated for the acute management of hyperammonemia and its safety/efficacy for NAGS deficiency has not been established, which is why the policy excludes use in those settings.

Definitions and Indication Notes

inv-16: UCD definition

DefinitionUrea cycle disorders (UCDs) are caused by inherited deficiencies of urea-cycle enzymes that impair conversion of nitrogen to urea.

Examples of enzyme deficienciesIncludes carbamyl phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), argininosuccinate lyase (ASL), argininosuccinate synthetase (AS), N-acetylglutamate synthase (NAGS), and arginase deficiencies.

Clinical consequenceEnzyme defects can lead to hyperammonemia due to impaired nitrogen disposal.

inv-17: Ravicti indication/limitations

IndicationRavicti (glycerol phenylbutyrate) is indicated for chronic management of patients with urea cycle disorders who cannot be managed by dietary protein restriction and/or amino acid supplementation alone.

Adjunctive use