Nitisinone

POLICY NUMBER

L.5.01.454

Orfadin (nitisinone)

Nityr (nitisinone)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Nitisinone is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme in the tyrosine catabolic pathway. By inhibiting the normal catabolism of tyrosine in patients with hereditary tyrosinemia type I (HT-1), nitisinone prevents the accumulation of catabolic intermediates, which would otherwise be converted to toxic metabolites. These toxic metabolites are responsible for the observed liver and kidney toxicity seen in these patients.

Nitisinone is indicated for the treatment of patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

The following medications are not covered on any BCBSMS Formulary:

• Nityr (nitisinone)

Initial Criteria

Orfadin (nitisinone) may be considered medically necessary when ALL of the following:

1. The individual has a documented diagnosis of hereditary tyrosinemia type 1 (HT-1) as evidenced by

   ONE of the following:

2. Elevated succinylacetone in the urine or blood; OR

3. Genetic testing confirms biallelic pathogenic/likely pathogenic variants in the fumarylacetoacetate hydrolase (FAH) gene;

4. The requested medication will be used in combination with dietary restriction of tyrosine and phenylalanine;

5. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent;

   AND

6. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage for the formulation being used.

Length of Approval: 6 months

Renewal Criteria

Orfadin (nitisinone) may be approved for continuation when ALL of the following criteria are met:

1. The individual has previously been approved for therapy through BCBSMS PA process;

2. The requested medication will be used in combination with dietary restriction of tyrosine and phenylalanine;

3. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

4. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage for the formulation being used.

Length of approval: 12 months

POLICY EXCEPTIONS

State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at  https://www.dfa.ms.gov/cvs-caremark  and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Member, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

POLICY HISTORY

4/16/2002: Approved by Pharmacy & Therapeutics (P & T) Committee

9/12/2006: Updated Accredo contact information.

9/21/2006: Coding updated. ICD9 2006 revisions added to policy.

1/3/2007: Code reference section updated per the 2007 CPT/HCPCS revisions.

01/01/2009: Accredo preferred provider information removed. BCBSMS information added.

04/02/2014: Policy reviewed; no changes. Removed deleted ICD-9 Diagnosis code 775.8 from the Code Reference section.

08/17/2015: Medical policy revised to add ICD-10 codes. Removed ICD-9 diagnosis codes 775.81 and 775.89 from the Code Reference section.

05/27/2016: Policy number L.5.01.454 added. Policy Guidelines updated to add medically necessary definition.

06/13/2016: Approved by Pharmacy & Therapeutics (P&T) Committee.

05/16/2017: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

12/19/2017: Policy updated to add Nityr™.

03/27/2018: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

08/04/2020: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy description revised. Policy section updated to add that the use of samples by a Member will not be considered current or stable therapy for purposes of Medical Policy review. Medically necessary policy statement criteria revised. Added renewal criteria for Nityr and Orfadin. Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

06/27/2024: Policy updated to extend Length of Approval to 6 months.

10/01/2024: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Added statement to please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan. Policy statements updated to change "member" to "individual." Medically necessary criteria updated regarding FDA-labeled contraindications and dose requirements. Second policy statement revised to replace "Nityr or Orfadin" with "Nitisinone" for consistency. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders." Sources updated. Effective 12/01/2024.

10/31/2025: Effective 01/01/2026 - Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy statement criteria revised to add additional renewal criteria. Added documentation of variants in the FAH gene to support diagnosis of hereditary tyrosinemia type 1. Policy update effective 01/01/2026.

SOURCE(S)

1. Chinsky JM, Singh R, Ficicioglu C, van Karnebeek CDM, Grompe M, Mitchell G, Waisbren SE, Gucsavas-Calikoglu M, Wasserstein MP, Coakley K, Scott CR. Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med. 2017 Dec;19(12). doi: 10.1038/gim.2017.101. Epub 2017 Aug 3. PMID: 28771246; PMCID: PMC5729346.

2. de Laet C, Dionisi-Vici C, Leonard JV, et al. Recommendations for the management of tyrosinaemia type 1. Orphanet J Rare Dis. 2013;8:8. Published 2013 Jan 11. doi:10.1186/1750-1172-8-8.

3. Nityr prescribing information. Cycle Pharmaceuticals Ltd. May 2024. Last accessed June 2025.

4. Orfadin prescribing information. Swedish Orphan Biovitrum AB. November 2021. Last accessed 

   June 2025.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s)  listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

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