Pharmacy Prior Authorization Criteria

Urea Cycle Disorder Agents - PA, NF

Indications for Prior Authorization

Buphenyl (sodium phenylbutyrate)

• For diagnosis of Urea cycle disorders (UCDs)
  Indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). It is indicated in all patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease (partial enzymatic deficiency, presenting after the first month of life) who have a history of hyperammonemic encephalopathy. It is important that the diagnosis be made early and treatment initiated immediately to improve survival. Any episode of acute hyperammonemia should be treated as a life-threatening emergency.

Pheburane (sodium phenylbutyrate)

• For diagnosis of Urea cycle disorders (UCDs)
  Indicated as adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients with urea cycle disorders (UCDs), involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC) or argininosuccinic acid synthetase (AS). Limitations of use: Episodes of acute hyperammonemia may occur in patients while on Pheburane. Pheburane is not indicated for the treatment of acute hyperammonemia, which can be a life-threatening medical emergency that requires rapid acting interventions to reduce plasma ammonia levels.

Ravicti (glycerol phenylbutyrate)

• For diagnosis of Urea cycle disorders (UCDs)
  Indicated for use as a nitrogen-binding agent for chronic management of patients with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Ravicti must be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements). Limitations of use: Ravicti is not indicated for the treatment of acute hyperammonemia in patients with UCDs because more rapidly acting interventions are essential to reduce plasma ammonia levels. The safety and efficacy of Ravicti for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.

Olpruva (sodium phenylbutyrate)

• For diagnosis of Urea cycle disorders (UCDs)
  Indicated for use as a nitrogen-binding agent, as an adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients weighing 20 kg or greater and with a body surface area (BSA) of 1.2 m or greater, with urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS).

  Limitations of Use: Olpruva is not indicated for the treatment of acute hyperammonemia

Criteria

Brand Buphenyl, generic sodium phenylbutyrate tablet

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)

• Both of the following:
• Diagnosis of urea cycle disorder (UCD)
AND
• One of the following deficiencies:
• carbamylphosphate synthetase (CPS)
• ornithine transcarbamylase (OTC)
• argininosuccinic acid synthetase (AS)
AND
• Molecular genetic testing confirms mutations in the CPS1, OTC, or ASS1 gene [2]
AND
• Trial and failure, or intolerance to generic sodium phenylbutyrate powder
AND
• Used as an adjunct with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements)
AND
• Prescribed by or in consultation with a specialist focused on the treatment of metabolic disorders

Pheburane

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)

• Both of the following:
• Diagnosis of urea cycle disorder (UCD)
AND
• One of the following deficiencies:
• carbamylphosphate synthetase (CPS)
• ornithine transcarbamylase (OTC)
• argininosuccinic acid synthetase (AS)
AND
• Molecular genetic testing confirms mutations in the CPS1, OTC, or ASS1 gene [2]
AND
• Used as an adjunct with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements)
AND
• Prescribed by or in consultation with a specialist focused on the treatment of metabolic disorders

Olpruva, Ravicti

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)

• Both of the following:
• Diagnosis of urea cycle disorder (UCD)
AND
• One of the following deficiencies:
• carbamylphosphate synthetase (CPS)
• ornithine transcarbamylase (OTC)
• argininosuccinic acid synthetase (AS)
AND
• Molecular genetic testing confirms mutations in the CPS1, OTC, or ASS1 gene [2]
AND
• Inadequate response to one of the following:
• Dietary protein restriction
• Amino acid supplementation
AND
• One of the following:
• Both of the following:
• Patient is 18 years of age or older
AND
• Trial and failure, contraindication, or intolerance to BOTH of the following:
• generic sodium phenylbutyrate powder
• Pheburane
OR
• Both of the following:
• Patient is less than 18 years of age
AND
• Trial and failure, contraindication or intolerance to one of the following:
• Generic sodium phenylbutyrate powder
• Pheburane
AND
• Used as an adjunct with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements)
AND
• Prescribed by or in consultation with a specialist focused on the treatment of metabolic disorders

Brand Buphenyl, generic sodium phenylbutyrate tablet, Pheburane

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)

• Patient demonstrates positive clinical response to therapy (e.g., plasma ammonia and amino acid levels within normal limits)
AND
• Used as an adjunct with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements)
AND
• Trial and failure, or intolerance to generic sodium phenylbutyrate powder [Applies to Brand Buphenyl and generic sodium phenylbutyrate tablet only]

Olpruva, Ravicti

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)

• Patient demonstrates positive clinical response to therapy (e.g., plasma ammonia and amino acid levels within normal limits)
AND
• Used as an adjunct with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements)
AND
• One of the following:
• Both of the following:
• Patient is 18 years of age or older
AND
• Trial and failure, contraindication, or intolerance to BOTH of the following:
• generic sodium phenylbutyrate powder
• Pheburane
OR
• Both of the following:
• Patient is less than 18 years of age
AND
• Trial and failure, contraindication or intolerance to one of the following:
• generic sodium phenylbutyrate powder
• Pheburane

Buphenyl

Non Formulary

Length of Approval: 12 Month(s)

• Submission of medical records (e.g., chart notes) confirming both of the following:
• Diagnosis of urea cycle disorder (UCD)
AND
• One of the following deficiencies:
• carbamylphosphate synthetase (CPS)
• ornithine transcarbamylase (OTC)
• argininosuccinic acid synthetase (AS)
AND
• Submission of medical records (e.g., chart notes) confirming molecular genetic testing confirms mutations in the CPS1, OTC, or ASS1 gene [2]
AND
• Paid claims or submission of medical records (e.g., chart notes) confirming trial and failure, or intolerance to generic sodium phenylbutyrate powder
AND
• Used as an adjunct with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements)
AND
• Prescribed by or in consultation with a specialist focused on the treatment of metabolic disorders

Olpruva, Ravicti

Non Formulary

Length of Approval: 12 Month(s)

• Submission of medical records (e.g., chart notes) confirming both of the following:
• Diagnosis of urea cycle disorder (UCD)
AND
• One of the following deficiencies:
• carbamylphosphate synthetase (CPS)
• ornithine transcarbamylase (OTC)
• argininosuccinic acid synthetase (AS)
AND
• Submission of medical records (e.g., chart notes) confirming molecular genetic testing confirms mutations in the CPS1, OTC, or ASS1 gene [2]
AND
• Inadequate response to one of the following:
• Dietary protein restriction
• Amino acid supplementation
AND
• One of the following:
• All of the following:
• ONE of the following:
• Patient is new to Ravicti or Olpruva therapy
• Patient has not previously been approved for Ravicti or Olpruva prior authorization with OptumRx
AND
• ONE of the following:
• Both of the following:
• Patient is 18 years of age or older
AND
• Paid claims or submission of medical records (e.g., chart notes) confirming trial and failure, contraindication, or intolerance to BOTH of the following:
• generic sodium phenylbutyrate powder
• Pheburane
OR
• Both of the following:
• Patient is less than 18 years of age
AND
• Paid claims or submission of medical records (e.g., chart notes) confirming trial and failure, contraindication or intolerance to one of the following:
• Generic sodium phenylbutyrate powder
• Pheburane
OR
• All of the following:
• Previously been approved for a prior authorization for Ravicti or or Olpruva
• Patient demonstrates positive clinical response to therapy (e.g., plasma ammonia and amino acid levels within normal limits)
• Used as adjunct with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements)
AND
• Prescribed by or in consultation with a specialist focused on the treatment of metabolic disorders

P & T Revisions

2024-06-05, 2024-01-12, 2024-01-12, 2024-01-09, 2024-01-03, 2023-11-03, 2023-07-25, 2023-05-03, 2023-03-01, 2022-10-26, 2022-05-05

References

1. Buphenyl Prescribing Information. Ucyclyd Pharma, Inc. Scottsdale, AZ. April 2023.
2. Ah Mew N, Simpson KL, Gropman AL, et al. Urea Cycle Disorders Overview. 2003 [updated 2017]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A, eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2022. Urea Cycle Disorders Overview - GeneReviews® - NCBI Bookshelf (nih.gov). Accessed April 11, 2022.
3. Häberle 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):1192-1230. doi: 10.1002/jimd.12100.
4. Ravicti [Prescribing Information]. Horizon Pharma USA, Inc. Lake Forest, IL. September 2021.
5. Pheburane Prescribing Information. Medunik USA, Inc. Bryn Mawr, PA. August 2023.
6. Olpruva Prescribing Information. Acer Therapeutics Inc.. Newton, MA. December 2022.
7. UpToDate. Urea Cycle Disorders Management. Available at:https://www.uptodate.com/contents/urea-cycle-disorders-management?search=urea%20cycle%20disorders&source=search_result&selectedTitle=2~42&usage_type=default&display_rank=2. Accessed July 11, 2023.
8. Olpruva manufacturer Website. Available at: https://olpruva.com/?utm_source=google&utm_medium=cpc&utm_campaign=OLPRUVA+Patient+Launch&utm_content=Now+Available&utm_keyword=olpruva&utm_id=engage&gclid=EAIaIQobChMI5K700NKCgAMVUQx9Ch3R2AXrEAAYAiAAEgITp_D_BwE. Accessed July 11, 2023.

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Revision History

• 2024-06-05: 2024 Annual Review - updated NF criterias and PA T/F requirements
• 2024-01-12: Update to criteria language to make clinical intent more clear.
• 2024-01-12: Update to criteria language to make clinical intent more clear.
• 2024-01-09: Update to criteria language with no change to clinical intent.
• 2024-01-03: Program update to standard reauthorization language. No changes to clinical intent.
• 2023-11-03: Modify PA for Ravicti and Olpruva; Modify NF for Ravicti; Apply drug-specific NF for Olpruva
• 2023-07-25: New UM PA Criteria for Olpruva
• 2023-05-03: 2023 Annual Review
• 2023-03-01: Update to Pheburane embedded step requirement
• 2022-10-26: Updated guideline
• 2022-05-05: New program

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