NITYR, Nitisinone ORFADIN, Nitisinon Form

Nitisinone (Nityr®, Orfadin®) is a hydroxy-phenylpyruvate dioxygenase inhibitor. FDA Approved Indication(s) Nityr and Orfadin are indicated for the treatment of adult and pediatric patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Nityr and Orfadin are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Hereditary Tyrosinemia Type 1 (must meet all):

1. Diagnosis of HT-1 as confirmed by one of the following (a or b): a. Genetic testing confirms a mutation of the FAH gene; b. Biochemical testing confirms elevated levels of succinylacetone in blood or urine;The lower limit of normal for succinylacetone is laboratory- and/or treatment center-specific; refer to laboratory- or clinic-specific reference ranges to determine elevated levels.
   2. Prescribed by or in consultation with an endocrinologist or a metabolic or genetic disease specialist;
2. Request is for use as an adjunct to dietary restriction of tyrosine and phenylalanine;
   4. Member is not using two different nitisinone products concurrently;
   5. For requests for Nityr and Orfadin 2 mg, 5 mg, or 10 mg strengths, member must use generic nitisinone, unless contraindicated or clinically significant adverse effects are experienced;
3. Dose does not exceed 2 mg/kg per day. Approval duration: 6 months
   B. Other diagnoses/indications (must meet 1 or 2):

4. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: Page 1 of 5

   CLINICAL POLICY
   Nitisinone
   CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

5. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Hereditary Tyrosinemia Type 1 (must meet all):
   
   1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
   2. Member is responding positively to therapy;
   3. Request is for use as an adjunct to dietary restriction of tyrosine and phenylalanine;
   4. Member is not using two different nitisinone products concurrently;
   5. For requests for Nityr and Orfadin 2 mg, 5 mg, or 10 mg strengths, member must use generic nitisinone, unless contraindicated or clinically significant adverse effects are experienced;
6. If request is for a dose increase, new dose does not exceed 2 mg/kg per day.
   Approval duration: 12 months
   B. Other diagnoses/indications (must meet 1 or 2):
7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

8. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line Page 2 of 5

   CLINICAL POLICY
   Nitisinone
   of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration HT-1: hereditary tyrosinemia type 1 Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Dosing Regimen Drug Name 0.5 mg/kg PO BID Generic nitisinone (Orfadin, Nityr) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Dose Limit/ Maximum Dose 2 mg/kg Appendix C: Contraindications/Boxed Warnings None reported V. Dosage and Administration
   Drug Name Nitisinone (Nityr) Nitisinone (Orfadin) Dosing Regimen 0.5 mg/kg PO BID 0.5 mg/kg PO BID Maximum Dose 2 mg/kg 2 mg/kg
   VI. Product Availability
   Drug Name Nitisinone (Nityr) Nitisinone (Orfadin) Availability Tablets: 2 mg, 5 mg, 10 mg Capsules: 2 mg, 5 mg, 10 mg, 20 mg Oral suspension: 4 mg/mL VII.