J Clin Pharmacol
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Risk factors for the development of specific noncardiovascular adverse effects associated with amiodarone

JE Tisdale, SL Follin, A Ordelova, and CR Webb

Noncardiovascular adverse effects associated with amiodarone result in substantial morbidity. Adverse effects involving the skin, liver, thyroid, and lungs have been reported in as many as 57%, 55%, 11%, and 13% of patients, respectively. Although risk factors for some amiodarone-induced adverse effects have been identified, risk factors for these specific side effects have not been systematically evaluated. Therefore, risk factors for development of amiodarone-induced dermatologic, hepatic, thyroid, or pulmonary adverse effects were identified using univariate analysis in 44 patients receiving the drug for supraventricular or ventricular arrhythmias (mean duration of therapy 99.5 +/- 110.8 weeks). Dermatologic side effects occurred in 4 (9.1%) patients. Patients who experienced dermatologic side effects were younger than patients who did not (mean age, 48.3 +/- 15.8 years versus 60.1 +/- 9.5 years, respectively; P = .03). Patients younger than 60 years of age were more likely to develop photosensitivity or blue-gray skin discoloration than those aged 60 or older (P = .05). Hepatic adverse effects occurred in 3 (6.8%) patients. Left ventricular ejection fraction was lower in those who developed hepatic adverse effects than in those who did not (15.0 +/- 4.0% versus 39.1 +/- 13.9%, P = .005). Adverse thyroid effects occurred in 6 (13.6%) patients; and pulmonary fibrosis occurred in 2 (4.5%) patients. No specific risk factors for adverse thyroid effects or pulmonary fibrosis were revealed. In conclusion, age less than 60 may be a risk factor for amiodarone-induced dermatologic adverse effects, whereas severely depressed left ventricular ejection fraction may be a risk factor for hepatic side effects associated with amiodarone.
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