Hepatitis amodiaquine

Toxicity by metabolism is not confined to the liver since oxidative systems occur in many organs and cells. Amodiaquine is a 4-aminoquinoline antimalarial that has been associated with hepatitis and agranulocytosis. Both side-effects are probably triggered by reactive metabolites produced in the liver or in other sites of the body. For instance polymorphonuclear leucocytes can oxidize amodiaquine. It appears that amodiaquine is metabolized to a quinone imine by the same pathway as that seen in... 

The principal reason against recommending amodiaquine for malaria prophylaxis is the reporting of agranulocytosis, occasionally associated with hepatitis (SEDA-12, 241) (SED-12, 692). Since specific IgG antibodies, which lead to leukopenia, can be detected, aU this suggests that the agranulocytosis is immune-mediated. 

Jewell H, Maggs JL, Harrison AC et al (1995) Role of hepatic metabolism in the bioactivation and detoxication of amodiaquine. Xenobiotica 25 199-217 follow DJ, Mitchell JR, Zampaglione N et al (1974) Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11 151-169... 

Larrey D, Castot A, Pessayre D et al (1986) Amodiaquine-induced hepatitis. A report of seven cases. Ann Intern Med 104 801-803... 

Larosche I, Letteron P, Fromenty B, Vadrot N, Abbey-Toby A, Feldmatm G, Pessayre D, Mansouri A (2007) Tamoxifen inhibits topoisrantaases, depletes mitochondrial DNA, and triggers steatosis in mouse liver. J Pharmacol Exp Ther 321 526-535 Larrey D, Castot A, Pessayre D, Merigot P, Machayekhy JP, Feldmarm G, Lenoir A, Rueff B, Benhamou JP (1986) Amodiaquine-induced hepatitis. A report of seven cases. Atm Intern Med 104 801-803... 

The prolonged use of amodiaquine hydrochloride in the dosages necessary to treat lupus erythematosus and rheumatoid arthritis is not recommended, for corneal opacities and retinopathy, peripheral neuropathy, fatal blood (fyscrasias, and fatal hepatitis have been reported after these large dc ag (47). Patients have experienced involuntary movements, usually with speech difficulty, after large but not excessive doses of amodiaquine (48). It may cause birth defects if taken during pregnancy (49). 

Liver The risk of hepatitis in patients taking long-term amodiaquine has been estimated at one in 15 500, and two further cases have been reported in patients with malaria who were also given artesunate [2 ]. 

Gu6vart E, Agu6mon A. Deux hepatites fulminantes survenues au cours d un traite-ment curatif par I association art6sunate-a-modiaquine. [Two cases of fulminant hepatitis during a curative treatment with an artesunate-amodiaquine combination.] Med Mai Infect 2009 39(1) 57-60. 

---