title: Fulminant hepatitis and fatal toxic epidermal necrolysis (Lyell disease) coincident with clarithromycin administration in an alcoholic patient receiving disulfiram therapy.
abstract: Disulfiram is widely used in the treatment of chronic alcoholism. Adverse drug reactions with fatal outcome following disulfiram therapy are infrequent, and hepatic failure accounts for most of them. Since disulfiram is a cytochrome P450 (CYP450) enzyme system inhibitor, numerous interactions with several drugs metabolized in the liver have been reported. Like disulfiram, clarithromycin inhibits a CYP450 isoenzyme, but, despite its widespread use for the treatment of respiratory tract infections, no interactions with disulfiram have been described as yet. We report a case of fatal toxic epidermal necrolysis (Lyell disease) and fulminant hepatitis shortly after starting treatment with clarithromycin in a patient who was receiving disulfiram. This is the first case of such a severe dermatosis in a patient receiving either disulfiram or clarithromycin therapy. The temporal relationship between drug administration and clinical symptoms in this case suggests a probable interaction between the 2 drugs.
authors.affiliation: Infectious Diseases Unit, Department of Internal Medicine, Hospital General Universitario de Elche, Partida Huertos y Molinos s/n, 03202 Elche, Alicante, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Masiá
authors.forename: Félix
authors.initials: F
authors.lastname: Gutiérrez
authors.forename: Araceli
authors.initials: A
authors.lastname: Jimeno
authors.forename: Andrés
authors.initials: A
authors.lastname: Navarro
authors.forename: Joaquín
authors.initials: J
authors.lastname: Borrás
authors.forename: Jaime
authors.initials: J
authors.lastname: Matarredona
authors.forename: Alberto
authors.initials: A
authors.lastname: Martín-Hidalgo
mesh_terms: D000427:Alcohol Deterrents / Q000009:adverse effects* / Q000493:pharmacokinetics; D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D017291:Clarithromycin / Q000009:adverse effects* / Q000493:pharmacokinetics; D065607:Cytochrome P-450 Enzyme Inhibitors; D004221:Disulfiram / Q000009:adverse effects* / Q000493:pharmacokinetics; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D008875:Middle Aged; D013262:Stevens-Johnson Syndrome / Q000209:etiology*
chemical_list: D000427:Alcohol Deterrents; D000900:Anti-Bacterial Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D017291:Clarithromycin; D004221:Disulfiram