Nitisinone
- Atc Codes:A16AX04
- CAS Codes:104206-65-7
- PHARMGKB ID:104206-65-7
Table of contents
- Brand Names
- Chemistry
- Pharmacologic Category
- Mechanism of Action
- Therapeutic Use
- Pregnancy and Lactation Implications
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Toxicological Effects
- Genes that may be involved
- Nutrition/Nutraceutical Interactions
- Dosage
- Pharmacokinetics and Pharmacodynamics
- Special Considerations
Brand Names
Europe
Austria: Orfadin; Belgium: Orfadin; Bulgaria: Orfadin; Cyprus: Orfadin; Czech Republic: Orfadin; Denmark: Orfadin; Estonia: Orfadin; Finland: Orfadin; France: Orfadin; Germany: Orfadin; Greece: Orfadin; Hungary: Orfadin; Ireland: Orfadin; Italy: Orfadin; Latvia: Orfadin; Lithuania: Orfadin; Luxembourg: Orfadin; Malta: Orfadin; Netherlands: Orfadin; Poland: Orfadin; Portugal: Orfadin; Romania: Orfadin; Slovakia: Orfadin; Slovenia: Orfadin; Spain: Orfadin; Sweden: Orfadin; UK: Orfadin.
North America
USA: Orfadin.
Drug combinations
Chemistry
Nitisinone: C~14~H~10~F~3~NO~5~. Mw: 329.23. (1) 1,3-Cyclohexanedione, 2-[2-nitro-4-(trifluoromethyl)benzoyl]-; (2) 2-(α,α,α-Trifluoro-2-nitro-p-tuluoyl)-1,3-cyclohexanedione. CAS-104206-65-7 (2002).
Pharmacologic Category
Other Miscellaneous Therapeutic Agents; 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor. (ATC-Code: A16AX04).
Mechanism of action
In hereditary tyrosinemia type 1 (HT-1), tyrosine metabolism is interrupted due to lack of enzyme (fumarylacetoacetate hydrolase) needed in last step of tyrosine degradation. Toxic metabolites of tyrosine accumulate and cause liver and kidney toxicity. Nitisinone competitively inhibits 4-hydroxyphenyl-pyruvate dioxygenase, enzyme needed earlier in tyrosine degradation pathway; therefore prevents build-up of damaging metabolites.
Therapeutic use
Treatment of hereditary tyrosinemia type 1. To be used with dietary restriction of tyrosine and phenylalanine.
Pregnancy and lactiation implications
Safety and efficacy not established for pregnant women. Use only if potential benefit to mother outweighs possible risk to fetus. Excretion in breast milk unknown (use caution).
Unlabeled use
Contraindications
Hypersensitivity to nitisinone or any component of the formulation.
Warnings and precautions
Transient leukopenia and/or thrombocytopenia may occur. Must be used with dietary restriction of tyrosine and phenylalanine (inadequate restriction can result in toxic effects to eyes, skin, and nervous system).