The Food and Drug Administration on Oct. 13 issued a warning about the “possible” risk of the rare atypical femur fractures associated with bisphosphonate treatment in osteoporosis patients, after reviewing the final report on this association released Sept. 14 by the American Society for Bone and Mineral Research.
The FDA has requested that a warning about the association be added to the labels of all bisphosphonates approved for osteoporosis prevention and treatment, and that a medication guide explaining the risk and the symptoms of these fractures be provided to patients with each bisphosphonate prescription, said Dr. Sandra Kweder during the briefing.
The agency also is requiring a change to the “indications and usage” section of the bisphosphonate labels, which will note that the optimal duration of treatment with bisphosphonates is not clear when they are used to treat and/or prevent osteoporosis.
In March 2010, the FDA announced that it was reviewing reports of femur fractures associated with bisphosphonate use, and the report issued by an American Society for Bone and Mineral Research (ASBMR) task force concluded that long-term bisphosphonate treatment may be related to an increased risk of these fractures, described as atypical fractures of the subtrochanteric region of the hip and femoral shaft (http://onlinelibrary.wiley.com/doi/10.1002/jbmr.253/pdf
The ASBMR report “helped us understand these fractures a little bit better and makes us confident that this is something that is potentially more closely related to these drugs, particularly [during] long-term use, than we previously had evidence for,” said Dr. Kweder, deputy director of the Office of New Drugs in the FDA's Center for Drug Evaluation and Research.
These fractures affect the femoral shaft, are less likely to be associated with trauma than are typical osteoporotic fractures, are sometimes bilateral, and generally affect younger patients, she said. Affected patients have described dull aching thigh or groin pain weeks to months before complete fracture is identified, she noted. The data indicate that they are more common in patients who have been on treatment for more than 5 years.
Similar to the recommendations in the ASBMR report, the FDA's recommendations to health care professionals include evaluating any patient who presents with new thigh or groin pain for a femur fracture, stopping treatment in patients with evidence of a femoral shaft fracture, and periodically reevaluating the need for continued treatment, particularly in patients treated for more than 5 years.
The products affected are those approved for osteoporosis indications, such as alendronate (Fosamax), alendronate and cholecalciferol (Fosamax Plus D), risedronate sodium (Actonel), risedronate sodium with calcium carbonate (Actonel with Calcium), ibandronate sodium (Boniva), risedronate sodium (Atelvia), pamidronate injection (Aredia), and zoledronic acid injection (Reclast), as well as generic formulations of those drugs.
The FDA advisory is available at www.fda.gov/Drugs/DrugSafety/ucm229009.htmwww.fda.gov/medwatch/