CurrentmhnPolicy CP.PHAR.206

Carglumic Acid (Carbaglu)

Policy governing medical necessity criteria, dosing, and approval durations for carglumic acid (Carbaglu) for treatment of hyperammonemia due to NAGS deficiency and as adjunctive therapy for propionic acidemia and methylmalonic acidemia; applies to members under Centene-affiliated health plans.

Policy Summary

Payermhn

PolicyCarglumic Acid (Carbaglu) therapy for hyperammonemia

Policy CodePolicy CP.PHAR.206

Change TypeAnnual review — no material changes noted

Effective Date05.01.16

Next Review Date

Key ActionSubmit prior authorization with documentation confirming diagnosis (enzymatic, biochemical, or genetic), current weight (kg), and prescribing clinician specialty.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 monthsNAGS maintenance approval

7 daysPA/MMA initial approval

100–250 mg/kg/dayNAGS initial dose range

200 mgtablet strength

1Q 2026most recent review

Coverage Criteria

Initial therapy — NAGS (UCD)

Covered when ALL of the following are met for NAGS-related UCD:

NAGS initial: 1. Diagnosis of a urea cycle disorder (UCD) caused by NAGS deficiency; 2. NAGS deficiency is confirmed by enzymatic, biochemical, or genetic analysis; 3. Prescribed by or in consultation with a physician experienced in treating metabolic disorders; 4. If request is for treatment of acute hyperammonemia, prescribed as adjunctive therapy with other ammonia-lowering therapies (e.g., alternative pathway drugs, hemodialysis, and dietary protein restriction); 5. If request is for brand Carbaglu, member must use generic carglumic acid unless contraindicated or clinically significant adverse effects are experienced; 6. Documentation of member's current weight (in kg); 7. Dose does not exceed 250 mg per kg per day initially, followed by a maintenance dose of 100 mg per kg per day.dose limits specified

Initial dose range and maintenance dosing per policy; titrate to maintain plasma ammonia within age-normal range

Reauthorization — NAGS (UCD)

Re-authorization covered when ALL of the following are met:

NAGS reauthorization: 1. Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria, or (b) member is currently receiving medication and continuity of care regulations apply per state/product; 2. Member is responding positively to therapy; 3. If request is for brand Carbaglu, member must use generic carglumic acid unless contraindicated or clinically significant adverse effects are experienced; 4. Documentation of member's current weight (in kg); 5. If request is for a dose increase, dose does not exceed a maintenance dose of 100 mg per kg per day.maintenance dose ≤100 mg/kg/day

Approval duration: 12 months (see limits by line of business)

Initial therapy — PA/MMA

Covered when ALL of the following are met for PA or MMA:

PA/MMA initial: 1. Diagnosis of propionic acidemia (PA) or methylmalonic acidemia (MMA); 2. Diagnosis is confirmed by urine organic acid, genetic, or enzymatic analysis; 3. Prescribed by or in consultation with a physician experienced in treating metabolic disorders; 4. Plasma ammonia level ≥ 70 micromol/L despite standard of care treatment (e.g., intravenous hydration and nutritional support); 5. Prescribed as adjunctive therapy to standard of care (e.g., IV glucose, insulin, L-carnitine, protein restriction, dialysis); 6. If request is for brand Carbaglu, member must use generic carglumic acid unless contraindicated or clinically significant adverse effects are experienced; 7. Documentation of member's current weight (in kg); 8. If member's weight is > 15 kg, documentation of member's current body surface area (BSA); 9. Dose does not exceed one of the following: (a) weight ≤ 15 kg: 150 mg/kg/day for 7 days; (b) weight > 15 kg: 3.3 g/m2/day for 7 days.plasma ammonia ≥70 micromol/L; treatment duration ≤7 days

Approval duration: 7 days; reauthorization not permitted

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless there is sufficient documentation of efficacy and safety in accordance with applicable off‑label use policies (for example, CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or by plan Evidence of Coverage documents.

When state Medicaid coverage provisions conflict with this clinical policy, the state Medicaid coverage provisions take precedence over the policy.

Re‑authorization for requests related to propionic acidemia (PA) or methylmalonic acidemia (MMA) is not permitted; members must meet the initial approval criteria for PA/MMA each time. Uses not listed in this policy are considered not authorized unless supported by applicable off‑label policies or Evidence of Coverage documents.

Confirmation of NAGS deficiency or PA/MMA via genetic analysis is accepted to establish diagnosis for coverage

Confirmation of diagnosis by genetic testing is acceptable to establish coverage when the following are met:

Genetic confirmation: 1. Genetic analysis confirming NAGS deficiency, or genetic analysis supportive of PA or MMA, is accepted as an appropriate method to establish the diagnosis for coverage; 2. Genetic testing results should be documented in the clinical record submitted with the authorization request (e.g., laboratory report); 3. Testing should be ordered by or in consultation with a physician experienced in treating metabolic disorders; 4. Genetic confirmation may be used in lieu of enzymatic or biochemical confirmation per the specific indication.

No additional eligibility statements are specified for genetic testing beyond the diagnostic confirmation requirements included in the coverage criteria.

Provider Actions and Documentation Requirements

Documentation Required

Provider Documentation Required

Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. Failure to submit documentation supporting that the member has met all approval criteria may trigger denial. Non‑FDA approved indications require sufficient documentation of efficacy and safety per applicable off-label use policies (e.g., CP.CPA.09 for commercial, HIM.PA.154 for HIX, CP.PMN.53 for Medicaid) or applicable evidence of coverage documents.

Office chart notes
Relevant lab results (enzymatic, biochemical, genetic, urine organic acids, plasma ammonia)
Documentation of current weight (kg) and/or body surface area (BSA) when required
Evidence of prior/adjunctive therapies when applicable

Prior Authorization

Adjunctive Therapy Requirement

If request is for treatment of acute hyperammonemia due to NAGS deficiency, carglumic acid must be prescribed as adjunctive therapy with other ammonia‑lowering therapies (e.g., alternative pathway drugs, hemodialysis, and dietary protein restriction). For organic acidemias (PA or MMA) carglumic acid must be prescribed as adjunctive therapy to standard of care (e.g., intravenous glucose, insulin, L‑carnitine, protein restriction, dialysis).

Adjunctive therapies for NAGS acute hyperammonemia: alternative pathway drugs, hemodialysis, dietary protein restriction
Adjunctive therapies for PA/MMA: IV glucose, insulin, L‑carnitine, protein restriction, dialysis

Note

Coverage and Prescribing Requirements

If the request is for brand Carbaglu, member must use generic carglumic acid unless contraindicated or clinically significant adverse effects are experienced. Prescriptions should be written by or in consultation with a physician experienced in treating metabolic disorders for covered indications. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions, and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

Brand-to-generic redirection required unless contraindication or adverse reaction documented
Prescriber requirement: physician experienced in metabolic disorders for covered indications
Coverage subject to plan terms, exclusions, limitations, and applicable laws/regulations

OpenPayer

Carglumic Acid (Carbaglu)

Coverage Criteria

Provider Actions and Documentation Requirements

Not Covered

Background

Definitions and Abbreviations