WHA

Nitisinone Products

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

*For patients who have difficulties swallowing intact tablets, including pediatric patients, the tablets can be disintegrated in water and administered using an oral syringe. If patients can swallow semi-solid foods, the tablets can also be crushed and mixed with applesauce. For preparation and administration instructions, see the full prescribing information [1].

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

*For patients who have difficulties swallowing intact tablets, including pediatric patients, the tablets can be disintegrated in water and administered using an oral syringe. If patients can swallow semi-solid foods, the tablets can also be crushed and mixed with applesauce. For preparation and administration instructions, see the full prescribing information.

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
  • 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)

  • Guideline ID
    GL-346197

  • Formulary
    ehb

  • Effective date
    Sep 1, 2025

  • P&T approval date
    Apr 18, 2018

P & T Revisions

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.
  1. In clinical trials, the diagnosis of alkaptonuria was based upon urinary HGA excretion greater than 0.4 g/24h. [5]
  • 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