Update of Safety Review of Bisphosphonates

The FDA announced on October 1, 2007 plans to review safety data surrounding the use of bisphosphonates and an apparent increased risk of atrial fibrillation.  This review was planned following the publication of an article and accompanying letter to the editor in the May 3, 2007 issue of The New England Journal of Medicine describing increased rates of atrial fibrillation in two separate studies of women aged 65 to 89 years old with osteoporosis that were being treated with Reclast or Fosamax.  Increased risk of serious atrial fibrillation was present in the data available to the FDA during that time, and this risk was included in the labeling of Reclast.  However, after review of the current data, the FDA recommends that health care professionals should not change their prescribing patterns for bisphosphonates, nor should patients stop taking their prescribed bisphosphonate therapy. 

Data was submitted to the FDA by the four sponsors of placebo-controlled clinical trials of alendronate, ibandronate, risedronate, and zoledronic acid in order to further investigate the potential risk for atrial fibrillation in male and female patients treated with these medications.  The data submitted included 19,687 bisphosphonate-treated patients and 18,358 placebo-treated patients that were followed for 6 months to 3 years.  Atrial fibrillation occurrence in each study was rare, with most studies having 2 or fewer occurrences.  The absolute difference in event rates between each of the bisphosphonate and placebo arms was reported to vary between 0-3 per 1,000.  There has been one large study of zoledronic acid which reported a statistically significant increase in the rate of serious atrial fibrillation events, however there appears to be no clear association across all studies.  The FDA stated that it was aware of the conflicting results in the literature and other studies about the incidence and outcomes of atrial fibrillation in patients taking bisphosphonates, and it is continuing to examine the issue. 

References:
1) www.fda.gov

Prepared by: Jen Curtis, PharmD. Candidate