Nitisinone Dipharma (Nitisinone)

Nitisinone acts on the tyrosine degradation pathway and is indicated for the following conditions:

• Hereditary tyrosinemia type I: reduces accumulation of toxic metabolites and improves liver function.
• Alkaptonuria (investigational): aims to lower homogentisic acid production and mitigate disease progression.

• Nitisinone inhibits the enzyme p‑hydroxyphenylpyruvate dioxygenase (HPPD), a key step in the catabolism of tyrosine. By blocking this enzymatic conversion, the drug prevents formation of downstream toxic metabolites such as fumarylacetoacetate, thereby reducing hepatic and systemic toxicity associated with hereditary tyrosinemia type I and related disorders.

Nitisinone may cause a range of adverse reactions. Patients should be monitored for both frequent and less common events.

Common Side Effects

• Headache: mild to moderate intensity.
• Nausea: may occur after dosing.
• Vomiting: occasional, often self‑limiting.
• Abdominal pain: mild discomfort reported.
• Fatigue: general tiredness.
• Elevated liver enzymes: mild transaminase rise.

Serious or Rare Side Effects

• Hepatic failure: signs of severe liver injury.
• Severe skin reactions: such as Stevens‑Johnson syndrome.
• Hypersensitivity: rash, pruritus, or anaphylaxis.
• Elevated serum tyrosine: may lead to ocular complications.
• Neurological disturbances: rare encephalopathy.
• Metabolic acidosis: uncommon but serious.

Before initiating therapy, clinicians should consider several safety measures.

• Liver function monitoring: assess baseline and periodic transaminases.
• Serum tyrosine levels: regular measurement to avoid excessive accumulation.
• Dietary protein restriction: limit high‑tyrosine foods as advised.
• Concomitant medications: review for potential interactions affecting metabolism.
• Pregnancy and lactation: use only if benefits outweigh risks, as data are limited.
• Store at ambient temperature: keep below 25°C in the original container, protect from moisture and direct sunlight.

Nitisinone can interact with other medicines; awareness of the interaction level helps guide management.

Major Interactions (Avoid)

• Other HPPD inhibitors: combined use may increase toxicity.
• Highly protein‑bound drugs: competition may alter plasma concentrations.
• Drugs causing hepatic injury: additive risk to liver function.

Moderate Interactions (Monitor Closely)

• Antihypertensives: monitor blood pressure for changes.
• Oral contraceptives: efficacy may be reduced, consider alternative methods.
• Vitamin A supplements: monitor for signs of excess.
• Warfarin: observe INR values for potential variation.