The three main complications of long-term amiodarone use are pulmonary toxicity, thyroid disease and liver toxicity. Rarely ocular problems and a bluish discoloration of the skin can occur.

Pulmonary toxicity is slowly progressive in the setting of amiodarone use, may be subtle initially and is the most common cause of death related to amiodarone therapy. It can take months to years of amiodarone therapy to develop and occurs in about 1-5% of patients taking 200 mg daily and as many as 15% taking > 400 mg daily. It can manifest as chronic interstitial pneumonitis or mmc pulmonary fibrosis. Routing pulmonary function testing is not recommended as it has not been shown to be accurate  enough to predict/prevent amiodarone lung toxicity. Amiodarone lung toxicity is a diagnosis of exclusion and treatment includes simply withdrawing amiodarone. Steroids can be used in severe cases. A majority of patients improve significantly once amiodarone is stopped.

Thyroid toxicity in the setting of amiodarone therapy can be either hyperthyroidism or hypothyroidism. One way to remember that amiodarone affects the thyroid is to recall how important iodine is to thyroid function. AmIODarone (as the name indicates), has a large amount of iodine. About 3-5% of patients on amiodarone develop hyperthyroidism and about 5% develop hypothyroidism. Amiodarone induced hypothyroidism can be easily treated with thyroid replacement therapy however hyperthyroidism must be considered further. If amiodarone is being used to treat life-threatening arrhythmia, then it is continued and the hyperthyroidism is treated medically. If the amiodarone is being used to treat a more benign rhythm disturbance, then alternative therapy should be used.

Hepatotoxicity with amiodarone is seen in about 25% of patients in the form of aminotransferase (AST and ALT) elevation. Amiodarone should be stopped if there is more than a 2-fold increase in these levels. Liver failure and cirrhosis can occur and it is thought that cumulative dose/long term therapy increases this risk.