FDA Panel: Update Bisphosphonate Labeling



ADELPHI, MD. – Data on the safety and effectiveness of bisphosphonate drugs for the long-term treatment of osteoporosis is lacking and direly needed, according to a joint Food and Drug Administration advisory committee meeting.

Specifically, the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 17-6 on Sept. 9 that labeling for these drugs should be changed to clarify the duration of use for this drug class.

The agency convened the joint meeting to evaluate particular concerns about the long-term use bisphosphonate drugs, given reports of atypical subtrochanteric and femoral fractures, jaw osteonecrosis, and esophageal cancer associated with bisphosphonate use.

The labels of bisphosphonate drugs – alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast) – already include "important limitation of use" information. This labeling states that the optimal duration of treatment (for an individual drug) has not been determined and that all patients on bisphosphonate therapy should be periodically reassessed for the necessity of continued therapy.

While the panel voted to clarify the label language, they were emphatic that much more data are needed to establish the long-term efficacy and safety of bisphosphonates in general and with special regard to atypical fractures, jaw osteonecrosis, and esophageal cancer.

The two committees also were asked to assess the strength of data on the long-term use of bisphosphonates; the overall risks and benefits of continuous long-term use (3-5 years or more); whether restricting the duration of use or implementing a drug holiday would be beneficial; which outcomes require further evidence; and how should this data be obtained.

The expert consensus is that existing data – some of which go out to roughly 10 years for one drug – do not address the efficacy of the long-term use of bisphosphonates. They recommended that (in no particular order) additional data are needed with regard to the occurrence of atypical fractures, osteonecrosis of the jaw, esophageal cancer, osteoporotic fracture reduction efficacy with long-term (at least 3-5 years) continuous bisphosphonate use, and the effect of a "drug holiday" on drug safety and effectiveness.

Osteoporosis currently affects approximately 10 million Americans, according to the American Society for Bone and Mineral Research. An additional 34 million have low bone mass, which may progress to osteoporosis.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally a panelist may be given a waiver, but none were given at this meeting.

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