The Food and Drug Administration will seek data for an “in-depth evaluation” of atrial fibrillation for the entire bisphosphonate class of drugs as well as continue to monitor any spontaneous postmarketing reports of the heart rhythm disorder, agency officials announced on Oct. 1.
FDA is not recommending at this point that physicians alter their prescribing choices or that patients change their medications.
The review encompasses products approved primarily to treat osteoporosis, slow bone turnover in Paget's disease, and treat bone metastases in cancer patients—specifically alendronate (Fosamax and Fosamax Plus D), risedronate (Actonel and Actonel with Calcium), ibandronate (Boniva), zoledronic acid (Reclast and Zometa), pamidronate (Aredia), and etidronate.
The evaluation follows publication of two studies describing increased rates of serious atrial fibrillation in older women treated with zoledronic acid or alendronate for osteoporosis (N. Engl. J. Med. 2007;356:1809–33 and N. Engl. J. Med. 2007;356:1895–6). In those studies, researchers found that more women who received one of the bisphosphonates developed serious atrial fibrillation versus those receiving placebo, according to the FDA announcement, which noted that overall rates of atrial fibrillation were not statistically different between the studies' active treatment and placebo arms.
Upon reviewing its postmarketing reports of atrial fibrillation in association with both oral and intravenous bisphosphonates, the agency did not find a “population of bisphosphonates users at increased risk” for the atrial fibrillation. And since atrial fibrillation is a common disorder in patients over age 65 years—the same population that was studied in the New England Journal of Medicine articles—the FDA cautioned that it is “unclear how these data … should be interpreted.”
Further, the FDA's recent review and approval of zoledronic acid included data on possible associations with atrial fibrillation, the agency said.
Those reviews found that most incidents occurred more than a month after infusion of the drug, which is administered once yearly to treat postmenopausal osteoporosis.
The in-depth review may take up to 12 months, according to the FDA. This is the agency's second “early communication” of a drug safety review, part of FDA's efforts to be more transparent in oversight of postmarketing drug safety. The first communication, which was released in August, addressed the proton pump inhibitors omeprazole and esomeprazole.
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