Nitisinone

(USAN, rINN)
Nitisinone Chemical formula
Synonyms: Nitisinonum; NTBC; SC-0735. 2-(α,α,α-Trifluoro-2-nitroptoluoyl)-1,3-cyclohexanedione.
Cyrillic synonym: Нитизинон.

💊 Chemical information

Chemical formula: C14H10F3NO5 = 329.2.
CAS — 104206-65-7.
ATC — A16AX04.
ATC Vet — QA16AX04.

💊 Profile

Nitisinone is a 4-hydroxyphenylpyruvate dioxygenase inhibitor used in the management of hereditary tyrosinaemia type 1; dietary restriction of tyrosine and phenylalanine is also necessary. An initial daily dose of 1 mg/kg given orally is recommended; daily dosage should be given in 2 divided doses, which may be unequally split. Monitoring of urine succinylacetone and plasma alpha-fetoprotein, as well as liver function tests, must be carried out. If necessary, the daily dose may be increased to 1.5 mg/kg after one month; the maximum daily dose is 2 mg/kg. If satisfactory results are obtained from biochemical testing, doses should only be increased in line with body-weight gain. Adverse effects have included granulocytopenia, leucopenia, and thrombocytopenia; regular monitoring of platelet and white cell counts is recommended. Eye disorders may occur due to increases in plasma tyrosine; they include conjunctivitis, corneal opacity, keratitis, photophobia, and eye pain. Slit-lamp examination of the eyes is recommended before starting treatment; patients developing visual disturbances during treatment should be referred to an ophthalmologist immediately, and further dietary restrictions implemented if plasma tyrosine is too high. Although it is not known if nitisinone is excreted into human milk, breast feeding is contra-indicated because of the potential effects on a suckling child. Nitisinone is under investigation for the treatment of alkaptonuria, another hereditary metabolic disorder.
1. Holme E, Lindstedt S. Tyrosinaemia type I and NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione). J Inherit Metab Dis 1998; 21: 507–17
2. Phornphutkul C, et al. Natural history of alkaptonuria. N Engl J Med 2002; 347: 2111–21.
3. Gissen P, et al. Ophthalmic follow-up of patients with tyrosinaemia type I on NTBC. J Inherit Metab Dis 2003; 26: 13–16
4. Joshi SN, Venugopalan P. Experience with NTBC therapy in hereditary tyrosinaemia type I: an alternative to liver transplantation. Ann Trop Paediatr 2004; 24: 259–65
5. Suwannarat P, et al. Use of nitisinone in patients with alkaptonuria. Metabolism 2005; 54: 719–28
6. McKiernan PJ. Nitisinone in the treatment of hereditary tyrosinaemia typ
1. Drugs 2006; 66: 743–50.

💊 Preparations

Proprietary Preparations

Belg.: Orfadin; Cz.: Orfadin; Denm.: Orfadin; Fin.: Orfadin; Fr.: Orfadin; Ger.: Orfadin; Neth.: Orfadin; Port.: Orfadin; Spain: Orfadin; Swed.: Orfadin; USA: Orfadin.
Published May 08, 2019.