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Urea Cycle Disorders Prior Authorization Program Summary
Policy Number: PH-1080
This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx, and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
7/1/2023 |
|
FDA APPROVED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Buphenyl®ª (sodium phenylbutyrate) Oral tablet Powder for oral, nasogastric, or gastrostomy tube administration |
|
ª – generic equivalent available |
2 |
Pheburane® (sodium phenylbutyrate) Oral pellets |
|
|
7 |
Ravicti® (glycerol phenylbutyrate) Oral liquid |
|
|
1 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
Urea Cycle Disorders |
Urea cycle disorders (UCDs) are rare genetically inherited metabolic deficiencies that result from defects in the metabolism of waste nitrogen from the breakdown of protein and other nitrogen-containing molecules. Severe deficiency, or total absence, of any of the enzymes in the urea cycle (carbamoyl phosphate synthetase I [CPS1], ornithine transcarbamylase [OTC], argininosuccinic acid synthetase [ASS1], argininosuccinic acid lyase [ASL], arginase [ARG1]) or the cofactor producer (N-acetyl glutamate synthetase [NAGS]) results in the accumulation of ammonia (hyperammonemia) during the first few days of life. In severe disease, infants rapidly develop cerebral edema and signs of lethargy, anorexia, hyper- or hypoventilation, hypothermia, seizures, neurologic posturing, and coma, whereas milder disease and the associated accumulation of ammonia may be triggered by illness or stress.(3-5) The most important diagnostic step in UCDs is clinical suspicion of hyperammonemia. Laboratory data useful in the diagnosis of UCD includes, but is not limited to, plasma ammonia, anion gap, and plasma glucose. A normal anion gap and normal blood glucose in the presence of a plasma ammonia concentration of 150 micomol/L (greater than 260 micrograms/dL) or higher in neonates and greater than 100 micromol/L (175 micrograms/dL) in older children and adults is indicative of UCD. The diagnosis of a specific UCD can be confirmed by genetic testing. Specifically, NAGS, OTC, and CPSI deficiencies can be confirmed by liver biopsy.(3-5) Pharmacologic therapy for acute hyperammonemia consists of initial IV administration of a combination preparation of sodium phenylacetate and sodium benzoate, ideally while the dialysis is being arranged and the diagnostic workup is under way. If chronic therapy is warranted, the patient can then be switched to nitrogen scavengers such as sodium phenylbutyrate, glycerol phenylbutyrate, and carglumic acid.(4-6) Sodium phenylbutyrate (Buphenyl) and glycerol phenylbutyrate (Ravicti) are metabolized to phenylacetate. Phenylacetate is a metabolically-active compound that conjugates with glutamine to form phenylacetylglutamine, which is then excreted by the kidneys. On a molar basis it is comparable to urea, which makes it an alternate vehicle for excreting waste nitrogen.(1,2) Long term management options to prevent hyperammonemia includes dietary modification and nutritional oversight (e.g., protein restriction, limitation of alcohol intake, essential amino acid supplementation if clinically appropriate).(4-6) Not all adult patients who recover from a hyperammonemic episode require chronic nitrogen scavengers, but they ought to be considered since many of these patients can become more brittle as time goes on.(4,5) |
Safety |
Sodium phenylbutyrate (Buphenyl) is contraindicated for management of acute hyperammonemia, which is a medical emergency.(2) Sodium phenylbutyrate (Pheburane) has no noted contraindications.(7) Glycerol phenylbutyrate (Ravicti) is contraindicated in patients with known hypersensitivity to phenylbutyrate.(1) |
REFERENCES
Number |
Reference |
1 |
Ravicti prescribing information. Horizon Therapeutics USA, Inc. September 2021. |
2 |
Buphenyl prescribing information. Horizon Therapeutics USA, Inc. March 2021. |
3 |
Ah Mew N, Simpson KL, Gropman AL, et al. Urea Cycle Disorders Overview. April 2003 [Updated June 2017]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1217/. |
4 |
Rare Diseases Clinical Research Network. Urea Cycle Disorders Consortium. Urea Cycle Disorders Treatment Guidelines. Available at: https://www.rarediseasesnetwork.org/cms/ucdc/Healthcare-Professionals/Urea-Cycle-Treatment-Guidelines. |
5 |
Summar M. Urea Cycle Disorders. National Organization for Rare Disorders (NORD). Available at: https://rarediseases.org/physician-guide/urea-cycle-disorders/. |
6 |
Haberle J, Burlina A, Chakrapani A, et al. Suggested Guidelines for the Diagnosis and Management of Urea Cycle Disorders: First Revision. J Inherit Metab Dis 2019;42(6):1041-1230. |
7 |
Pheburane prescribing information. Medunik USA, Inc. June 2022. |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Available MSC |
Final Age Limit |
Preferred Status |
|
||||||
Ravicti |
glycerol phenylbutyrate liquid |
1.1 GM/ML |
M ; N ; O ; Y |
N |
|
|
Buphenyl ; Pheburane |
sodium phenylbutyrate oral pellets ; sodium phenylbutyrate oral powder ; sodium phenylbutyrate tab |
3 GM/TSP ; 483 MG/GM ; 500 MG |
M ; N ; O ; Y |
N ; O ; Y |
|
|
CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Buphenyl ; Pheburane |
sodium phenylbutyrate oral pellets ; sodium phenylbutyrate oral powder ; sodium phenylbutyrate tab |
3 GM/TSP ; 483 MG/GM ; 500 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Ravicti |
glycerol phenylbutyrate liquid |
1.1 GM/ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
|
Initial Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 12 months
Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 12 months |
This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.
Commercial _ PS _ Urea Cycle Disorders Prior Authorization _ProgSum_ 7/1/2023