Centene glycerol phenylbutyrate Coverage Update

Coverage Criteria for Glycerol Phenylbutyrate (Ravicti)

inv-01: Initial Therapy

Covered when ALL of the following are met:

Initial UCD approval: 1) Diagnosis of a urea cycle disorder (UCD) caused by one or more of the following confirmed by enzymatic, biochemical, or genetic analysis: a) CPS1 deficiency; b) OTC deficiency; c) AS (classic citrullinemia/CTLN1) deficiency; d) ASL deficiency; e) Arginase deficiency; 2) Prescribed by or in consultation with a physician experienced in treating metabolic disorders; 3) If brand Ravicti is requested, member must use generic glycerol phenylbutyrate unless contraindicated or clinically significant adverse effects are experienced; 4) Member must currently be on dietary protein restriction; 5) For members with UCD caused by CPS1, OTC, or AS deficiency: a) member must use generic sodium phenylbutyrate unless contraindicated or clinically significant adverse events are experienced; b) if intolerant or contraindicated to generic sodium phenylbutyrate, member must use Pheburane unless contraindicated or clinically significant adverse effects are experienced; 6) Dose does not exceed 17.5 mL (19 g) per day.max 17.5 mL/day

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

inv-02: Continuation Therapy

Covered for continuation when ALL of the following are met:

Continuation UCD approval: 1) Member meets one of the following: a) currently receiving medication via Centene benefit or previously met initial approval criteria; b) currently receiving medication and enrolled in a state/product with continuity of care regulations; 2) For members with UCD caused by CPS1, OTC, or AS deficiency: a) member must use generic sodium phenylbutyrate unless contraindicated or clinically significant adverse events are experienced; b) if intolerant or contraindicated to generic sodium phenylbutyrate, member must use Pheburane unless contraindicated or clinically significant adverse effects are experienced; 3) Member is responding positively to therapy; 4) If brand Ravicti is requested, member must use generic glycerol phenylbutyrate unless contraindicated or clinically significant adverse effects are experienced; 5) Member must currently be on dietary protein restriction; 6) If request is for a dose increase, new dose does not exceed 17.5 mL (19 g) per day.max 17.5 mL/day

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

inv-03: Initial and continuation therapy requirements

Covered when ALL of the following are met

Dosing and indication: Use for urea cycle disorders with dosing per labeling: total daily dosage given in 3 divided doses (for phenylbutyrate-naïve patients 4.5-11.2 mL/m2/day; when converting from sodium phenylbutyrate use multipliers 0.81 for powder or 0.86 for tablets); do not exceed 17.5 mL/day.see node text

Dosage and conversion per labeling (chunk 18)

Formulary redirection: Member has trial of or redirection to generic glycerol phenylbutyrate and/or generic sodium phenylbutyrate per stepwise redirection; if intolerance or contraindication to generic sodium phenylbutyrate, member must use Pheburane prior to branded Ravicti except where redirection specifies generic glycerol phenylbutyrate.stepwise per policy

redirection updates and requirements (chunks 22,23)

Dietary management:

Ravicti (glycerol phenylbutyrate) is intended for chronic management of urea cycle disorders (UCDs) and is not indicated for treatment of acute hyperammonemia; faster-acting interventions are required in the acute setting. The policy also notes that safety and efficacy have not been established for certain specific enzyme deficiencies (for example, N-acetylglutamate synthase [NAGS] deficiency) where labeled data are lacking. Coverage decisions should follow these indication-specific limitations when evaluating requests for Ravicti.

Requests for Ravicti must meet the clinical criteria for UCD management described elsewhere in this policy (diagnostic confirmation, specialist involvement, dietary protein restriction, dosing within labeled limits). Use for acute hyperammonemia or for non‑labeled indications without documentation aligned to off‑label policies should not be authorized.

The policy does not list other explicit clinical exclusions beyond the acute hyperammonemia limitation and the NAGS note; however, branded Ravicti requests are subject to formulary redirection per the stepwise substitution rules (see step therapy and prior authorization sections). Recent updates added redirection to generic glycerol phenylbutyrate as an option prior to approval of the branded product, and continuation or initial requests may be redirected per the redirection requirements.

Use of Ravicti for non‑FDA approved indications that are not addressed by this policy will only be considered when the provider supplies sufficient documentation of efficacy and safety in accordance with Centene off‑label use policies (for example, CP.CPA.09 for commercial, HIM.PA.154 for marketplace, or CP.PMN.53 for Medicaid). Absent that documentation and an applicable evidence-of-coverage determination, such requests are not authorized.

The policy requires adherence to the documented stepwise redirection sequence for branded Ravicti. Failure to follow redirection—such as not trialing required generic alternatives (generic sodium phenylbutyrate, Pheburane when indicated, or generic glycerol phenylbutyrate as specified)—or lacking documentation of contraindication/intolerance to those alternatives may result in the request being considered not medically necessary. Providers should include documentation of prior trials or reasons for exemption when submitting prior authorization requests.

Initial Therapy

inv-22: Initial Therapy

Initial approval criteria for Ravicti

Initial therapy: Diagnosis of specified UCD confirmed by enzymatic, biochemical, or genetic analysis (CPS1, OTC, AS/CTLN1, ASL, arginase); prescribed by or in consultation with a physician experienced in metabolic disorders; member must be on dietary protein restriction; trials of generic alternatives per policy prior to brand use when applicable (generic sodium phenylbutyrate and/or generic glycerol phenylbutyrate as specified); dose within maximum limits (17.5 mL/day).max 17.5 mL/day

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

inv-23: Initial therapy — Initial authorization is granted when labeling dose and redirection requirements are met.

Initial authorization is granted when labeling dose and redirection requirements are met.

Initial therapy dosing: Dosing per labeling: total daily dosage in 3 equally divided doses; phenylbutyrate-naïve dosing 4.5-11.2 mL/m2/day; convert from sodium phenylbutyrate using multipliers (0.81 powder, 0.86 tablets); maximum 17.5 mL/day.

Continuation Therapy

inv-24: Continuation Therapy

Criteria required for continuing Ravicti therapy

Continuation: Member currently receiving medication via Centene benefit or previously met initial approval OR continuity of care applies; continued use requires documented positive response to therapy; ongoing dietary protein restriction; adherence to generic substitution/redirection requirements for Ravicti and sodium phenylbutyrate when applicable; dose must not exceed 17.5 mL/day.

inv-25: Continuation therapy — Continuation requests must follow redirection sequence and may require documentation of prior trials.

Continuation requests must follow redirection sequence and may require documentation of prior trials.

Continuation requirements: For continuation, redirection to generic sodium phenylbutyrate followed by Pheburane (if intolerance/contraindication) and/or generic glycerol phenylbutyrate may be applied per stepwise redirection; documentation of prior trials, intolerance, or contraindications and documentation of ongoing response and dietary management required; approval durations updated to 12 months for Commercial.

Step Therapy / Therapeutic Substitution

Step	Required trial(s) before approving brand Ravicti	Notes
1	Trial of generic glycerol phenylbutyrate OR generic sodium phenylbutyrate prior to approval of branded Ravicti	If member has UCD due to CPS1, OTC, or AS deficiency, generic sodium phenylbutyrate is specifically required unless contraindicated; if intolerant to generic sodium phenylbutyrate, Pheburane is required unless contraindicated. Dose must not exceed 17.5 mL (19 g) per day.

Step	Required redirection sequence	Notes / exceptions
1	Trial of generic sodium phenylbutyrate first; if intolerance or contraindication to generic sodium phenylbutyrate, member must use Pheburane. Redirection to generic glycerol phenylbutyrate is also required per 1Q2026 update.	Applies to initial and continuation requests; documentation of intolerance/contraindication required when bypassing prior agents. Dietary protein restriction per labeling is required.

Provider Actions, Prior Authorization & Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must document a diagnosis of a qualifying urea cycle disorder (UCD) confirmed by enzymatic, biochemical, or genetic analysis and that the prescriber is experienced in treating metabolic disorders or consulted with such a physician. For initial and continued therapy, dosing must follow policy dosing rules (total daily dose given in 3 equally divided doses; conversion from sodium phenylbutyrate to Ravicti per dosing table).

Prescriber: physician experienced in metabolic disorders or consultation documented
Dosing: total daily dose given in 3 equally divided doses; conversion from sodium phenylbutyrate per policy

Prior Authorization

Prior Authorization and Redirection

Requests for brand Ravicti may be redirected to generic alternatives. Documentation must show that redirection rules were followed and why branded Ravicti is required if redirection was unsuccessful.

Requests may be redirected to generic glycerol phenylbutyrate

Dosing Limits and Key Coding Values

Maximum daily dose

Maximum total daily volume17.5 mL/day (maximum dose)

Equivalent mass19 g/day (per policy note)

Dose divisionTotal daily dose given in 3 equally divided doses

Maximum daily dose (emphasis)

Emphasized maximum17.5 mL/day

Policy contextDose does not exceed 17.5 mL (19 g) per day

Approval requirementRequests for dose increases must not exceed 17.5 mL/day

Quantity Limits

glycerol phenylbutyrate (Ravicti) — quantity limit

ProductGlycerol phenylbutyrate (Ravicti) oral liquid

Maximum total daily volume17.5 mL/day

Dose formOral liquid formulation

Glycerol phenylbutyrate (Ravicti) — total daily volume

Total daily volume calculationTotal daily dosage given in 3 equally divided doses; calculate per dosing regimen

Conversion from sodium phenylbutyrateRavicti (mL) = sodium phenylbutyrate (g) x 0.81 (powder) or x 0.86 (tablets)

Maximum

Definitions and Dosing Notes

Nitrogen-binding agent used chronically in UCDs

DefinitionGlycerol phenylbutyrate is a nitrogen-binding (nitrogen scavenger) agent used chronically in the management of urea cycle disorders (Ravicti).

Indication contextUsed when dietary protein restriction and/or amino acid supplementation alone are insufficient (chronic management, not for acute hyperammonemia).

FormulationAvailable as an oral liquid formulation (Ravicti).

Definition of Urea Cycle Disorder (UCD)

DefinitionUrea cycle disorders (UCDs) are deficiencies of enzymes that convert nitrogen to urea.

Examples of enzyme deficienciesCarbamyl phosphate synthetase 1 (CPS1); Ornithine transcarbamylase (OTC); Argininosuccinate synthetase (AS/CTLN1); Argininosuccinate lyase (ASL); N-acetyl glutamate synthetase (NAGS); Arginase.

Site of Care

Note

Site of care — oral liquid for home/outpatient use

Ravicti is administered orally as an oral liquid formulation and is intended for home or outpatient use; ensure the claim/billing reflects oral liquid administration in the appropriate setting.

Oral liquid formulation (1.1 g/mL)
Appropriate site of care: home or outpatient setting

Background

Urea cycle disorders (UCDs) are inherited deficiencies of the hepatic enzymes that convert nitrogen to urea (examples include CPS1, OTC, AS, ASL, NAGS, and arginase), which can lead to chronic hyperammonemia. Glycerol phenylbutyrate (Ravicti) is a nitrogen‑binding agent indicated for chronic management of UCDs when dietary protein restriction and/or amino acid supplementation alone are insufficient; it is not for acute hyperammonemia management. Dosing follows labeling: total daily dose is given in three equally divided doses, conversions from sodium phenylbutyrate use specified multipliers, and the oral liquid concentration is 1.1 g/mL with a policy maximum of 17.5 mL/day. Dietary protein restriction per labeling is required as part of ongoing management.

Revision History

2024-11-07redirection_added

Per ad hoc SDC request, redirection to generic sodium phenylbutyrate followed by redirection to Pheburane was added for continuation requests.

2025-11-12annual_review

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

2025-11-14policy_revisionLatest

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Glycerol Phenylbutyrate (Ravicti) Coverage