Men taking amiodarone at increased risk for cancer

The antiarrhythmia drug amiodarone appears to be linked to a higher risk of cancer in men, specifically those who receive higher cumulative defined daily doses within the first year of treatment, according to a retrospective study published online April 8 in Cancer.

Compared with the general population, the overall risk of cancer for patients taking amiodarone did increase with a standardized incidence ratio of 1.12 (95% CI, 0.99-1.26; P=.067). However, the risk of all cancers was significantly higher in men than in women (SIR, 1.18; 95% CI, 1.02-1.36; P=.022; and SIR, 0.99; 95% CI, 0.79-1.23, respectively).

"When prescribing amiodarone, doctors need to keep in mind that this medication may increase cancer risk," lead study author Vincent Yi-Fong Su, MD, Taipei Veterans General Hospital, Taipei, Taiwan, told Formulary. "Patients who were male or who received high cumulative daily doses of amiodarone within the first year had an increased risk of developing cancer. Those with both factors were 46% more likely to develop cancer than those with neither factor."

After 3 years of follow-up, men who received cumulative defined daily doses in a year greater than 180 had a 46% higher risk of cancer (SIR, 1.46; 95% CI, 1.11-1.89; P=.008), reported Dr Su, MD, and colleagues.

In this study, more than 6,800 patients who received amiodarone for 28 or more days between January 1996 and December 2008 were identified from the National Health Insurance Research Database in Taiwan. The final cohort consisted of 6,418 patients, and approximately 57% were male. The median age at diagnosis was 70 years. The median follow-up was 2.57 years.

Patients had a number of comorbidities, including diabetes mellitus (39%), cirrhosis (3.2%), chronic pulmonary obstructive disorder (44%), chronic kidney disease (25%), heart failure (47%), hypertension (76%), and cardiovascular disease (72%).

Patients were followed until cancer occurrence, the end point of the study. At the end of 2008, there were 280 cancers diagnosed, 198 in men and 82 in women.

“In the current study, male patients had an increased risk of cancer, but female patients did not. One possible explanation for this difference is that there is a 37% higher clearance rate of amiodarone in females than in males because of differences in cytochrome P450 3A4 activity and the percentage of body fat,” the authors wrote.

In a multivariate analysis, age, cirrhosis, socioeconomic status, and cumulative daily doses of amiodarone also were associated with increased risk of cancer. However, the interactions between variables were not significant, Dr. Su reported.

“There is a dose-effect relation between amiodarone and cancer occurrence,” the authors concluded. “It should be noted that the evidence regarding amiodarone as a carcinogen is weak, because the HR is only 1.001 for one additional daily dose.”

The authors suggested that future amiodarone trials should report cancer events, and further research is warranted.