Nitisinone

Nitisinone is a medication used to treat hereditary tyrosinemia type I (HT-1). It inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) in the tyrosine degradation pathway, preventing the formation of toxic metabolites such as fumarylacetoacetate. By reducing the production of these toxic substances, nitisinone helps prevent liver and kidney damage that characterizes HT-1 and lowers the risk of liver failure and hepatocellular carcinoma. It can also reduce the need for liver transplantation when started early and used with dietary management.

Nitisinone is given by mouth, usually as a single daily dose or divided doses, and is combined with a diet restricted in tyrosine and phenylalanine to maintain safe tyrosine levels. Dosing is typically tailored to body weight and clinical response, with regular monitoring.

Ongoing management includes regular blood tests to check tyrosine concentration, liver and kidney function, and urinary levels of succinylacetone (a disease marker). Monitoring for ocular effects such as keratitis or photophobia is advised because high tyrosine levels can affect the cornea. Patients and caregivers are advised on dietary adherence and to report adverse effects promptly.

Nitisinone is marketed under the brand name Orfadin and is approved in many countries for HT-1. It has also been studied for other conditions, including alkaptonuria, but is not approved for these uses. As with any therapy, use during pregnancy or breastfeeding requires careful risk assessment.

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