Amiodarone Toxicity

The three main complications of long-term amiodarone use are pulmonary toxicity, thyroid disease and liver toxicity. 

Pulmonary toxicity progresses slowly 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 to develop and occurs in about 1% to 5% of patients taking 200 mg daily, and in as many as 15% taking > 400 mg daily. It can manifest as chronic interstitial pneumonitis or mimic pulmonary fibrosis. Routine pulmonary function testing is not recommended, as it has not been shown to be accurate enough to predict or prevent amiodarone lung toxicity. Amiodarone lung toxicity is a diagnosis of exclusion, and treatment includes simply withdrawing amiodarone, though steroids can be used in severe cases. A majority of patients improve significantly once amiodarone is stopped. The chest X-ray shows diffuse interstitial changes, sometimes with a predilection for the upper lobes.

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Amiodarone Lung Toxicity

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% to 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 treated more aggressively and amiodarone discontinuation is required. 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 such as atrial fibrillation, 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.

Bradycardia is a known effect of amiodarone. When given intravenously, the solvents polysorbate 80 and benzyl alcohol are thought to induce significant hypotension.

Rarely, ocular problems and a bluish discoloration of the skin can occur causing “blue man syndrome.” This can also occur from silver nitrate ingestion, or as a rare genetic disorder.

Mnemonic: Amiodarone Side-Effects + Toxicity are a "BITCH"

Bradycardia/Blue man
Interstitial Lung Disease
Thyroid (hyper and hypo)
Corneal (ocular)/Cutaneous (skin)
Hepatic/Hypotension when IV (due to solvents)

References:

1. Amiodarone: Guidelines fo Use and Monitoring. Am Fam Physician. 2003;68:2189-2197.
2. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, Tenth Edition, Saunders, Philadelphia, 2015.
3. Hassis et al. Side-effects of long-term amiodarone therapy. Circulation. 1983;67:45-51.
4. Hurst's The Heart, Thirteenth Edition, McGraw-Hill, 2011.