Orfadin (Nitisinone)

Nitisinone, the active ingredient in Orfadin, is a small‑molecule inhibitor presented as a tablet for oral use. It is employed in the management of hereditary tyrosinemia type 1 in patients who require lifelong metabolic control. GNH USA supplies Orfadin as a licensed, GDP‑compliant international pharmaceutical supplier serving hospitals, transplant centres and pharmacies worldwide.

GNH USA supplies Orfadin as a licensed, GDP‑compliant international pharmaceutical supplier serving hospitals, transplant centres and pharmacies worldwide.

Orfadin is used in the context of inherited metabolic disorders that affect the tyrosine degradation pathway.

- Hereditary tyrosinemia type 1: reduces the accumulation of toxic metabolites and helps prevent liver failure. - Acute hepatic crisis in HT‑1: lowers the risk of severe liver dysfunction during metabolic decompensation. - Long‑term disease management: supports sustained reduction of plasma succinylacetone levels, contributing to improved growth and development.

Adverse reactions to nitisinone are reported across a range of severity.

Common Side Effects: - Elevated alanine aminotransfer (ALT) and aspartate aminotransfer (AST) levels. - Headache. - Nausea or vomiting. - Skin rash. - Mild abdominal discomfort.

Serious or Rare Side Effects: - Severe liver injury or hepatitis. - Acute kidney injury. - Hypersensitivity reactions including anaphylaxis. - Significant elevation of serum tyrosine leading to ocular complications. - Metabolic acidosis. - Unexplained fever or systemic inflammatory response.

When prescribing Orfadin, clinicians should consider several safety measures.

- Baseline liver function testing: obtain prior to initiation and monitor regularly. - Serum tyrosine monitoring: maintain levels within recommended range to avoid ocular toxicity. - Renal function assessment: evaluate kidney parameters before starting therapy. - Dietary management: advise a low‑tyrosine, low‑phenylalanine diet to complement treatment. - Drug interaction vigilance: review concomitant medications that may affect liver enzymes. - Store at ambient temperature: keep tablets in the original container, protect from moisture and direct sunlight.

Nitisinone may interact with other medicines that influence hepatic metabolism or tyrosine levels.

Major Interactions (Avoid): - Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine): may reduce nitisinone exposure. - High‑tyrosine supplements or protein‑rich formulas: can counteract the drug’s metabolic effect.

Moderate Interactions (Monitor Closely): - Acetaminophen (paracetamol): may increase risk of liver enzyme elevation. - Warfarin: potential alteration of anticoagulant effect requiring INR monitoring. - NSAIDs: may add to hepatic stress when combined with nitisinone. - Certain antibiotics (e.g., fluoroquinolones): possible additive hepatotoxicity. - Herbal preparations containing St John’s wort: may modestly lower drug levels.