Men taking the antiarrhythmia drug amiodarone (Nexterone), particularly those with extensive exposure, have an increased risk for cancer, study results indicate.
Among men taking amiodarone, cancer risk increased 20% compared with the general population, with a standardized incidence ratio of 1.18 (95% CI: 1.02-1.36; P=0.022), Vincent Yi-Fong Su, MD, of Taipei Veterans General Hospital in Taiwan and colleagues reported in Cancer.
This risk was even higher among men whose cumulative daily doses exceeded 180 annually, at 46% (SIR 1.46, 95% CI: 1.11-1.89; P=0.008), the researchers found.
“We suggest that cancer events should be routinely reported in future amiodarone trials, and further observational research is necessary,” Su said in a press release. “Also, when prescribing amiodarone, doctors need to keep in mind that this medication may increase cancer risk.”
Since licensure, amiodarone has been associated with several potentially serious adverse events, including thyroid dysfunction, pulmonary fibrosis, and skin and thyroid malignancies. To further explore a possible cancer link, Su and colleagues analyzed data from 6,418 patients Taiwanese National Health Insurance Research Database who received a prescription for the drug between 1997 and 2008.
Median patient age was 70 years, and median follow up was 2.57 years. Comorbidities included hypertension (76%), heart failure (47%), chronic obstructive pulmonary disease (44%) and diabetes (39%). A total of 288 cancers were identified during the almost 22,000 person-years of follow-up.
There was an approximate 10% increase in risk for all cancers among patients who received amiodarone (SIR 1.12, 95% CI: 0.99-1.26, P=0.067), the researchers found. However, women did not appear to be at increased risk (SIR 99; 95% CI: 0.79-1.23).
Among men, elevated risk occurred among those aged 20 to 60 years (SIR 1.67; 95% CI: 1.07-2.48; P=0.025) and those older than 80 years (SIR 1.41; 95% CI: 1.07-1.83; P=0.016).
One reason for the gender disparity may be that women clear amiodarone faster than men, the researchers suggested.
Multivariate analysis revealed several factors associated with increased risk including: age (HR 1.04; P<0.001), male gender (HR 1.90; P<0.001), cirrhosis (HR 3.70; P<0.001), cumulative daily dosage (HR 1.001 for each additional dose; P=0.022) and socioeconomic factors.
When the risk associated with cumulative doses was further stratified into tertiles, patients in the intermediate and highest levels of amiodarone exposure had adjusted HRs of 1.70 (95% CI: 1.02-2.84, P=0.042) and 1.98 (95% CI: 1.22-3.22, P=0.006), respectively.
There were no differences in risk for specific types of cancer, including lung, thyroid and skin.