Amiodarone-induced Hepatitis and Polyneuropathy

Abstract

Amiodarone chlorhydrate is a diiodated benzofuran derivative, and it is used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone, and symptomatic hepatic dysfunction occurs in fewer than 1% of the patients taking amiodarone. Cirrhosis is a rare complication that's been confirmed in 12 cases. Peripheral neuropathy occurs in 10% of patients taking aminodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity and peripheral neurotoxicity. A 75 year old man with normal liver function was given amiodarone for treating his atrial fibrillation and heart failure. He developed nausea, vomiting, muscle weakness and wasting after 17.8 months therapy with amiodarone (400 mg orally once per day). Liver biopsy showed the presence of foam cells in the hepatic sinusoids and Mallory bodies in the periportal hepatocytes on light microscopy. Sural nerve biopsy showed demyelination, and nerve conduction studies showed mixed sensorimotor polyneuropathy. These observations show the necessity of monitoring the hepatic function and conducting neurologic examination of the patients treated with amiodarone.

Amiodarone neurotoxicity: the other side of the medal

“…Three patients of Fraser et al [1] during long-term high-dose therapy developed predominantly sensory neuropathy; high concentrations of amiodarone and its N-desethyl metabolite were found in lysosomes especially in tissues rich of macrophages. That is similar to Kang et al [2] patient who developed 17 months after receiving oral amiodarone, neuropathy and hepatitis; both conditions improved after drug cessation. In humans exposed to amiodarone, nerve conduction abnormalities vary from a predominant axonopathy, with reduced amplitudes of evoked responses, to prominent conduction slowing suggesting demyelination, to a mixed picture [1,2,7].…”

“…That is similar to Kang et al [2] patient who developed 17 months after receiving oral amiodarone, neuropathy and hepatitis; both conditions improved after drug cessation. In humans exposed to amiodarone, nerve conduction abnormalities vary from a predominant axonopathy, with reduced amplitudes of evoked responses, to prominent conduction slowing suggesting demyelination, to a mixed picture [1,2,7]. Inhibition of Complex 1 of respiratory chain and altered folate metabolism were proposed as one possible mechanism for toxicity [15].…”

“…Amiodarone's clinical efficacy has been tempered by its ubiquitous toxicity, with almost 50% of long-term users discontinuing the drug [1,2,[5][6][7]. Amiodarone toxicity might be function of cumulative dose administered, but it can occur shortly after drug initiation [1,2,[5][6][7]. We present two patients chronically exposed to oral amiodarone; both developed a progressing peripheral neuropathy associated with asymptomatic bilateral optic neuropathy.…”

“…Amiodarone hydrochloride, the most commonly prescribed anti-arrhythmic drug, is an iodinated benzofuran derivative prescribed at recommended dose of 200 mg daily; its direct action is to prolong repolarization and refractoriness in cardiac tissues, including the sinus, the atrium,the atrioventricular nodes, and the Purkinje system [1,5,6]. Amiodarone's clinical efficacy has been tempered by its ubiquitous toxicity, with almost 50% of long-term users discontinuing the drug [1,2,[5][6][7]. Amiodarone toxicity might be function of cumulative dose administered, but it can occur shortly after drug initiation [1,2,[5][6][7].…”

“…Side effects of anti-arrhythmic drugs may affect thyroid, lung, liver, eyes, central, and peripheral nervous system [1][2][3][4][5][6][7][8][9][10][11]. Amiodarone hydrochloride, the most commonly prescribed anti-arrhythmic drug, is an iodinated benzofuran derivative prescribed at recommended dose of 200 mg daily; its direct action is to prolong repolarization and refractoriness in cardiac tissues, including the sinus, the atrium,the atrioventricular nodes, and the Purkinje system [1,5,6].…”