Orfadin (Nitisinone)

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.

• Nitisinone blocks the enzyme 4‑hydroxyphenylpyruvate dioxygenase (HPPD) in the tyrosine catabolic pathway, preventing formation of downstream toxic metabolites such as fumaryl‑acetoacetate and succinyl‑acetone. By halting this step, the drug reduces hepatic and renal toxicity associated with hereditary tyrosine‑type 1 disorder.

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.