title: Three cases of severe acute hepatitis after parenteral administration of amiodarone: the active ingredient is not the only agent responsible for hepatotoxicity.
abstract: Amiodarone is one of the most effective antiarrhythmic drugs available and is widely prescribed despite several potentially life-threatening side-effects. Hepatotoxicity is the most frequent one during long-term oral therapy: occasionally acute hepatitis necessitates the suspension of treatment but monitoring of a transient increase in serum aminotransferases is usually sufficient; the clinical-morphological pictures of liver cirrhosis have also been reported. Fulminant hepatitis soon after a parenteral load of the drug is far less well described in the literature. Most published cases were reversible after the suspension of treatment. A negative challenge after oral amiodarone exposure suggested that polysorbate 80, a solvent added to the intravenous infusion and already implied in the pathogenesis of a similar syndrome observed in infants, is a more likely cause of this complication. The occurrence of acute hepatitis complicating parenteral amiodarone treatment does not preclude subsequent oral use of the drug: an evidence-based therapeutic behavior now definitively consolidated. Because of the rarity of this diagnosis, we report 3 cases of short-term hepatotoxicity secondary to amiodarone treatment for supraventricular tachyarrhythmias: in 2 male patients with dilated cardiomyopathy and in a female with liver disease. The diagnosis was presumptive and based on a thorough drug history, the temporal relationship, the time-course of liver dysfunction, the exclusion of other causes and on the rapid improvement observed after parenteral amiodarone withdrawal in 2 cases; in no case could we find any other explanation for the liver damage. Since amiodarone is sometimes still an irreplaceable antiarrhythmic drug, we raise the question of whether careful and continuous vigilance should be mandatory in patients receiving the drug or whether it is possible to introduce a pharmaceutical preparation not containing the vehicle that induces acute liver toxicity.
authors.affiliation: U.O. di Medicina Interna, Presidio Ospedaliero S.M.d.P. Incurabili. frank.giannattasio@libero.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Giannattasio
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvio
authors.forename: Maria
authors.initials: M
authors.lastname: Varriale
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Picciotto
authors.forename: Giovan Giuseppe
authors.initials: GG
authors.lastname: Di Costanzo
authors.forename: Mario
authors.initials: M
authors.lastname: Visconti
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000368:Aged; D000638:Amiodarone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001201:Ascites / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced; D005260:Female; D006529:Hepatomegaly / Q000139:chemically induced; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D014677:Pharmaceutical Vehicles / Q000009:adverse effects*; D011136:Polysorbates / Q000009:adverse effects*; D013614:Tachycardia, Paroxysmal / Q000188:drug therapy; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000889:Anti-Arrhythmia Agents; D014677:Pharmaceutical Vehicles; D011136:Polysorbates; D000638:Amiodarone