Nitisinone

What it is and how it works

Mechanism of Action Nitisinone is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme upstream of fumarylacetoacetate hydrolase (FAH) in the tyrosine catabolic pathway. By inhibiting the normal catabolism of tyrosine in patients with HT-1, nitisinone prevents the accumulation of the catabolic intermediates maleylacetoacetate and fumarylacetoacetate. In patients with HT-1, these catabolic intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate, which are responsible for the observed liver and kidney toxicity.

Mechanism class: Hydroxyphenylpyruvate Dioxygenase Inhibitors · Cytochrome P450 2C9 Inhibitors · Cytochrome P450 2E1 Inducers

Indications

Nitisinone capsules are indicated for the treatment of adult and pediatric patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine. Nitisinone capsules are a hydroxy-phenylpyruvate dioxygenase inhibitor indicated for the treatment of adult and pediatric patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.

Dosage and administration (summary)

Recommended Dosage : The recommended starting dosage is 0.5 mg/kg orally twice daily. In patients 5 years of age and older who have undetectable serum and urine succinylacetone concentrations after a minimum of 4 weeks on a stable dosage of nitisinone, the total daily dose may be given once daily. Titrate the dosage based on biochemical and/or clinical response, as described in the full prescribing information. The maximum total daily dosage is 2 mg/kg orally.

Contraindications

None. None

Warnings and precautions

Elevated Plasma Tyrosine Levels, Ocular Symptoms, Developmental Delay and Hyperkeratotic Plaques : Inadequate restriction of tyrosine and phenylalanine intake can lead to elevations in plasma tyrosine, which at levels above 500 micromol/L can result in symptoms, intellectual disability and developmental delay or painful hyperkeratotic plaques on the soles and palms; do not adjust nitisinone capsules dosage in order to lower the plasma tyrosine concentration. Obtain slit-lamp examination prior to treatment, regularly during treatment.

Pregnancy

Pregnancy Risk Summary Limited available data with nitisinone use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. Animal reproduction studies have been conducted for nitisinone.

Storage and supply

White capsules marked in blue with the following logo on the capsule cap: , and identified as 2 mg, 5 mg, 10 mg or 20 mg strengths of nitisinone on the capsule body. The capsules are packed in a high-density polyethylene container with a child-resistant polypropylene snap-on cap. Each bottle contains 60 capsules.

Source: Nitisinone (Nitisinone) — US FDA prescribing information, 2025-09-05, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.