Amiodarone ups risk of acute pancreatitis: study

Last Updated: 2015-01-21

By Megan Brooks

NEW YORK (Reuters Health) - Use of the antiarrhythmic amiodarone raises the risk of acute pancreatitis, according to a large observational study.

"Our results indicate that acute pancreatitis could be an adverse effect of amiodarone use, an effect that may not be shared by other antiarrhythmic drugs," Dr. Alvaro Alonso and colleagues from the University of Minnesota in Minneapolis say in a research letter online January 19 in JAMA Internal Medicine.

"Even though the absolute risk of acute pancreatitis in the general population is low, health care professionals should be aware of this potential association in the treatment of patients with NVAF (nonvalvular atrial fibrillation) or acute pancreatitis," they advise.

A few isolated case reports of acute pancreatitis possibly linked to amiodarone use have been reported in the literature, but the possible association hasn't been explored in a large study, until now.

Dr. Alonso and colleagues did a nested case-control study using health care utilization data. The 1686 case patients had NVAF and were admitted to the hospital with a primary diagnosis of acute pancreatitis between January 1, 2007 and December 31, 2012. Five control patients with NVAF were matched with each case patient (n=8430).

The use of amiodarone was associated with about a 50% increased odds of acute pancreatitis (odds ratio 1.53).

The odds were nearly doubled in the 12 months after amiodarone was initiated (multivariable odds ratio 1.86) and did not depend on cumulative use of amiodarone.

"Considering an incidence of acute pancreatitis of 3 to 4 cases per 10,000 adults per year, the observed association would result in approximately 1 to 2 additional cases of acute pancreatitis per 10,000 amiodarone users per year," the investigators say.

Acute pancreatitis was not associated with use of other antiarrhythmic drugs (ie, dronedarone, sotalol hydrochloride, flecainide, propafenone, or dofetilide).

"Because the incidence of acute pancreatitis is low, our findings do not really require a change in clinical practice," Dr. Alonso wrote in email to Reuters Health. "However, we believe that our findings should be considered by clinicians attending patients with acute pancreatitis (for example, considering amiodarone as a potential cause in patients taking this drug)."

"Also, our findings may indicate that other antiarrhythmics besides amiodarone could be more appropriate in patients with history of acute pancreatitis - though our results support this recommendation only indirectly," Dr. Alonso added.

The mechanism(s) underlying the association between acute pancreatitis and amiodarone are unclear, "although direct cytotoxicity or immune-mediated pathways, as described for amiodarone-related pulmonary toxic effects, could be potential explanations," the researchers say.

"Our findings do not provide direct evidence of a potential mechanism - assuming that the association was really causal," Dr. Alonso told Reuters Health. "We observed, though, that the association of amiodarone with increased pancreatitis risk was independent of cumulative exposure to pancreatitis and that the increased risk was mostly present soon after initiation of pancreatitis, which may support the presence of an idiosyncratic reaction. Studying the potential mechanisms for the association described in our paper could help identify patients more likely to develop this adverse effect and develop new drugs that do not have similar toxicity."

The study was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health and the University of Minnesota Academic Health Center. The authors have disclosed no conflicts of interest.

SOURCE: http://bit.ly/1BbHnv0

JAMA Intern Med 2015.