Nitisinone Dipharma (Nitisinone)

• Nitisinone acts on the tyrosine degradation pathway and is used primarily for hereditary tyrosinemia type I, a rare autosomal recessive metabolic disorder.
• Hereditary tyrosinemia type I: Inhibits formation of fumarylacetoacetate and succinylacetone, thereby decreasing hepatic toxicity, reducing risk of liver failure, and supporting normal growth and development in affected patients.
• Hereditary tyrosinemia type I (pre‑transplant): Used to lower toxic metabolite levels and improve liver function, facilitating safer liver transplantation when required.
• Hereditary tyrosinemia type I (post‑transplant maintenance): Continues therapy to prevent recurrence of metabolic complications.

• Nitisinone selectively inhibits the enzyme p‑hydroxyphenylpyruvate dioxygenase (HPPD) in the hepatic tyrosine catabolic pathway. By blocking this step, the conversion of p‑hydroxyphenylpyruvate to homogentisic acid is prevented, which halts the downstream production of toxic metabolites such as fumarylacetoacetate and succinylacetone. The resulting reduction in metabolite accumulation alleviates hepatic and renal toxicity associated with hereditary tyrosinemia type I.

Nitisinone may be associated with a range of adverse reactions, which are classified by frequency and severity.

Common Side Effects

• Headache: mild to moderate headache reported in some patients.
• Nausea: occasional nausea or upset stomach.
• Fatigue: general tiredness or reduced energy.
• Skin rash: mild dermatologic reactions such as erythema.

Serious or Rare Side Effects

• Hepatic failure: severe liver dysfunction requiring monitoring.
• Seizures: rare occurrence of convulsive episodes.
• Anaphylaxis: potentially life‑threatening allergic reaction.

When prescribing Nitisinone, clinicians should consider several precautionary measures to ensure patient safety.

• Liver function monitoring: assess hepatic enzymes before initiation and periodically during therapy.
• Renal impairment caution: adjust use in patients with reduced kidney function.
• Hypersensitivity risk: discontinue if signs of allergic reaction appear.
• Pregnancy considerations: safety not established; weigh potential benefits against risks.
• Specialist supervision: treatment should be managed by physicians experienced in metabolic disorders.
• Store below 25°C: keep in the original packaging, protect from moisture and direct sunlight.

Nitisinone can interact with other medicines, altering its effectiveness or increasing toxicity.

Major Interactions (Avoid)

• Warfarin: may potentiate anticoagulant effect and increase INR.
• Rifampicin: induces hepatic enzymes, reducing Nitisinone plasma levels.
• Phenobarbital: enzyme induction can lower therapeutic concentrations.

Moderate Interactions (Monitor Closely)

• NSAIDs: combined use may increase risk of renal impairment.
• Oral contraceptives: possible reduction in contraceptive efficacy, requiring additional protection.
• Vitamin K antagonists: monitor coagulation parameters for potential changes.