WHA
 

Nitisinone Products - PA, NF

Indications for Prior Authorization

Nityr (nitisinone) tablets
  • For diagnosis of Hereditary Tyrosinemia Type 1 (HT-1)
    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.

Brand Orfadin capsules, Brand Orfadin oral suspension, Generic nitisinone capsules
  • For diagnosis of Hereditary Tyrosinemia Type 1 (HT-1)
    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.

Harliku (nitisinone)
  • For diagnosis of Alkaptonuria (AKU)
    Indicated for the reduction of urine homogentisic acid (HGA) in adult patients with alkaptonuria (AKU).

Criteria

Nityr*, Brand Orfadin, Generic nitisinone

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Hereditary Tyrosinemia type 1 (HT-1)

  • Diagnosis of hereditary tyrosinemia type 1 (HT-1)
    • AND
  • Diagnosis confirmed by the presence of succinylacetone in the plasma or urine [1-3]
    • AND
  • Used in combination with dietary restriction of tyrosine and phenylalanine
    • AND
  • Prescribed by or in consultation with one of the following:
    • Gastroenterologist
    • Hepatologist
    • Other specialist with experience in treating inborn errors of metabolism
    AND
  • Applies to Nityr only; trial and intolerance to brand Orfadin
Nityr*, Brand Orfadin, Generic nitisinone

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Hereditary Tyrosinemia type 1 (HT-1)

  • Patient demonstrates a positive clinical response to therapy
    • AND
  • Applies to Nityr only; trial and intolerance to brand Orfadin
Harliku

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Alkaptonuria (AKU)

  • Diagnosis of alkaptonuria (AKU)
    • AND
  • Used for the reduction of urine homogentisic acid (HGA)
    • AND
  • Disease is confirmed by one of the following: [A]
    • Presence of a mutation in the homogentisate 1,2-dioxygenase (HGD) gene as detected by an FDA-approved test or a test performed at a facility approved by Clinical Laboratory Improvement Amendments (CLIA)
    • Presence of elevated homogentisic acid (HGA) levels in urine greater than 0.4 g/24h
    AND
  • Trial (of a minimum 30-day supply) or intolerance to generic nitisinone 2mg capsules [B,11]
    • AND
  • Prescribed by or in consultation with one of the following:
    • Rheumatologist
    • Geneticist
    • Specialist experienced in the treatment of inborn errors of metabolism
Harliku

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Alkaptonuria (AKU)

  • Patient demonstrates positive clinical response to therapy (e.g., reduced levels of urinary HGA)
    • AND
  • Trial (of a minimum 30-day supply) or intolerance to generic nitisinone 2mg capsules [B,11]
Harliku

Non Formulary

Length of Approval: 12 Month(s)
For diagnosis of Alkaptonuria (AKU)

  • Submission of medical records (e.g., chart notes) confirming diagnosis of alkaptonuria (AKU)
    • AND
  • Used for the reduction of urine homogentisic acid (HGA)
    • AND
  • Submission of medical records (e.g., chart notes) confirming disease with one of the following: [A]
    • Presence of a mutation in the homogentisate 1,2-dioxygenase (HGD) gene as detected by an FDA-approved test or a test performed at a facility approved by Clinical Laboratory Improvement Amendments (CLIA)
    • Presence of elevated homogentisic acid (HGA) levels in urine greater than 0.4 g/24h
    AND
  • Both of the following:
    • Submission of medical records (e.g., chart notes) confirming the patient has experienced intolerance (e.g., allergy to excipient) to generic nitisinone 2mg capsules that have the same active ingredient
      • AND
    • Submission of medical records (e.g. chart notes) confirming generic nitisinone 2mg capsules have not been effective AND valid clinical justification provided explaining how Harliku is expected to provide benefit when generic nitisinone 2mg has not been shown to be effective despite having the same active ingredient
    AND
  • Prescribed by or in consultation with one of the following:
    • Rheumatologist
    • Geneticist
    • Specialist experienced in the treatment of inborn errors of metabolism

  • Guideline ID
    GL-449253

  • Formulary
    ehb

  • Effective date
    Feb 1, 2026

  • P&T approval date
    Apr 18, 2018

P & T Revisions

2025-12-17, 2025-09-23, 2025-08-25, 2024-10-31, 2024-07-30, 2023-10-03, 2023-08-04, 2022-08-03, 2021-07-24, 2021-05-21, 2021-03-01, 2020-06-02, 2019-10-28

  1. Nityr prescribing information. Cycle Pharmaceuticals Ltd. Cambridge, UK. May 2024.
  2. Orfadin prescribing Information. Sobi Inc. Waltham, MA. November 2021.
  3. 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.
  4. Harliku prescribing information. Cycle Pharmaceuticals Ltd. Cambridge, UK. June 2025.
  5. ClinicalTrails.gov. Long-Term Study of Nitisinone to Treat Alkaptonuria. Available at: https://clinicaltrials.gov/study/NCT00107783?cond=NCT00107783&rank=1#participation-criteria. Accessed July 26, 2025.
  6. Alkaptonuria Society Alkaptonuria is a rare inherited disorder. Available at: https://akusociety.org/. Accessed July 26, 2025.
  7. Disorders of tyrosine metabolism: Clinical features, diagnosis, and management. Available at: https://www.uptodate.com/contents/disorders-of-tyrosine-metabolism-clinical-features-diagnosis-and-management?sectionName=ALKAPTONURIA&search=ALKAPTONURIA&topicRef=7196&anchor=H19&source=see_link#H19. Accessed July 26, 2025.
  8. Genetic and Rare Diseases Information Center. Alkaptonuria. Available at: https://rarediseases.info.nih.gov/diseases/5775/alkaptonuria. Accessed July 26, 2025.
  9. Wikipedia-Alkaptonuria. Available at: https://en.wikipedia.org/wiki/Alkaptonuria. Accessed July 26, 2025.
  10. Mishra, N. How to Diagnose Alkaptonuria: Urine Analysis and Genetic Testing. Available at: https://tap.health/how-to-diagnose-alkaptonuria-urine-analysis-and-genetic-testing/. Accessed July 26, 2025.
  11. Internal Research Response (RR) dated Sept 17, 2025 based on Clinical Consult from August 25, 2025. MD has experience in pediatrics, genetics, birth defects and metabolic disorder.
  1. In clinical trials, the diagnosis of alkaptonuria was based upon urinary HGA excretion greater than 0.4 g/24h. [5]
  2. Harliku is the only nitisinone product indicated for alkaptonuria (AKU). It was approved under a supplemental new drug application as a new indication for Nityr; however, the manufacturer has given it a unique brand name for this indication. Although there are no specific treatment guidelines for nitisinone products in the treatment of AKU, consultant feedback indicated that Harliku, Orfadin, and Nityr would be interchangeable, as they have the same active ingredient. [11]
  • 2025-12-17: Added IL statute operational note.
  • 2025-09-23: Annual review: No criteria changes.
  • 2025-08-25: Add drug Harliku to existing guideline
  • 2024-10-31: Added criterion to initial authorization and reauthorization: For Nityr only; trial and intolerance to brand Orfadin.
  • 2024-07-30: Annual review: No criteria changes. Updated references.
  • 2023-10-03: Program update to standard reauthorization language. No changes to clinical intent
  • 2023-08-04: Annual review: Added new 20mg nitisinone capsule (generic Orfadin) to mirror brand Orfadin criteria.
  • 2022-08-03: Annual review: No criteria changes. Updated references and background.
  • 2021-07-24: Updated references section.
  • 2021-05-21: Addition of EHB formulary to guideline, no changes to criteria
  • 2021-03-01: updated guideline to remove embedded step through Nityr for Brand Orfadin
  • 2020-06-02: Annual review: updated background & references
  • 2019-10-28: updated guideline to add generic nitisinone tablets