Nitisinone Dipharma (Nitisinone)

Nitisinone is used primarily in the management of disorders of tyrosine metabolism, specifically hereditary tyrosinemia type I.

• Hereditary tyrosinemia type I: reduces accumulation of toxic metabolites and improves liver function.
• Growth and development support: helps normalize growth parameters in affected children.
• Transplant delay: may postpone the need for liver transplantation by stabilizing disease progression.

• Nitisinone selectively inhibits the enzyme 4‑hydroxyphenylpyruvate dioxygenase (HPPD) in the hepatic tyrosine catabolic pathway. By blocking this step, the conversion of 4‑hydroxyphenylpyruvate to homogentisic acid is prevented, which stops the formation of downstream toxic metabolites such as maleylacetoacetate and fumarylacetoacetate. This reduction of toxic intermediates mitigates liver damage and other systemic effects associated with hereditary tyrosinemia type I.

Nitisinone may cause a range of adverse reactions, most of which are mild and reversible.

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Headache: transient cranial discomfort.
• Fatigue: generalized tiredness.
• Elevated liver enzymes: mild increase in hepatic transaminases.

Serious or Rare Side Effects

• Hepatic failure: severe liver dysfunction requiring monitoring.
• Pancreatitis: acute inflammation of the pancreas.
• Severe skin reactions: including Stevens‑Johnson syndrome.
• Neutropenia: significant reduction in white blood cells.
• Anaphylaxis: rare but potentially life‑threatening allergic response.
• Vision changes: rare disturbances in visual acuity.

Before initiating therapy, clinicians should consider several safety measures.

• Dose adjustment in hepatic impairment: monitor liver function tests regularly.
• Renal function monitoring: assess creatinine clearance as needed.
• Avoid use in patients with known hypersensitivity to nitisinone.
• Pregnancy and lactation: safety not established; weigh risks and benefits.
• Drug interactions: review concomitant medications for potential CYP interactions.
• Store at ambient temperature: keep in original container, protect from moisture and light.

Nitisinone can interact with other medicines, requiring attention to avoid reduced efficacy or increased toxicity.

Major Interactions (Avoid)

• Concomitant use with vitamin A supplements: may increase risk of hepatotoxicity.
• Strong CYP3A4 inducers (e.g., rifampicin): may reduce nitisinone exposure.
• Co‑administration with other HPPD inhibitors: additive toxicity risk.

Moderate Interactions (Monitor Closely)

• Anticoagulants (warfarin): may require INR monitoring.
• Diuretics: monitor electrolytes and renal function.
• Oral contraceptives: possible alteration of hormone levels.