An analysis of amiodarone, a drug commonly used as a treatment for arrhythmias, found a borderline elevated risk of cancer, which increased in men and in patients with higher cumulative daily doses of the drug. The results were published online April 8 in CANCER.

In 2004, the FDA issued a medication guide on amiodarone (Cordarone, Wyeth/Pfizer) that cited postmarket reports of thyroid cancer in patients treated with the antiarrhythmic drug. Animal studies, case reports and other research have investigated potential risks associated with amiodarone, including cancers. But Vincent Yi-Fong Su, MD, of Taipei Veterans Hospital in Taiwan, and colleagues noted that no large-scale study has examined the issue.

Yi-Fong Su et al used Taiwan’s comprehensive data resources to study the association between amiodarone treatment and the risk of cancer. Taiwan’s National Health Insurance program covers 98 percent of residents, and other databases such as the Catastrophic Illness Registry capture cancer diagnoses and pathologic confirmations of the disease.

The researchers identified 6,418 patients who received amiodarone treatment between 1996 and 2008; the patients were all 20 years old or older and had no known malignancies preceding enrollment. Median follow-up was 2.57 years. They calculated the standardized incidence ratio (the number of cancers in the study group divided by the number of expected cancers in the general population) to determine risk, and the correlation between the cumulative defined daily doses of amiodarone and cancer to identify risk predictors.

In that patient group, they found 280 cancers, a finding they defined as a borderline significant increase in cancer. That risk increased in male patients, particularly those with more than 180 cumulative defined daily doses of amiodarone within the first year of therapy.

Gender differences may account for the heightened risk in men, Yi-Fong Su et al proposed. Women have a higher clearance rate of amiodarone, they wrote, and hormonal differences also may be a factor.

The study did not find an association between amiodarone and any specific cancer, including thyroid cancer. They wrote that the number of cases of specific cancers was too small to provide reliable results.

Their analysis did not include potential risk factors for cancer such as smoking or obesity, and the follow-up period may have been too short to capture the growth of cancers. They recommended that future trials involving amiodarone also track cancer data.  

“The results of the current study demonstrate a higher cancer risk in patients, especially males, treated with higher cDDDs [cumulative defined daily doses] of amiodarone than in the general population,” they wrote. “There is a dose-effect relation between amiodarone and cancer occurrence. It should be noted that the evidence regarding amiodarone as a carcinogen is weak, because the HR [hazard ratio] is only 1.001 for one additional daily dose.”