Bisphosphonates - New Labeling Data On Long-term Usage Recommended By FDA Advisory Panel

Bisphosphonates, medications for the treatment and prevention of osteoporosis and other bone conditions, should have additional data on their labels on treatment duration, an FDA Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee (the Panel) recommended. However, the panel did not go as far as advising that specific time limits be included. Approximately 5 million Americans fill bisphosphonates prescriptions annually, and include such brand names as Fosamax, Reclast, Boniva, Altevia, Actonel, and Aclasta.

The meeting on bisphosphonates was convened in Adelphi, Maryland, in response to growing concern regarding the long-term use of these medications – when patients are on them for over three to five years. The FDA had received reports of bone death – osteonecrosis – of the jaw, as well as unusual thigh bone (femur) fractures in females who had been on bisphosphonates for several years.

According to some recent studies, women might still derive benefits from the effects of bisphosphonates for several years after they stop taking them because the active ingredient remains in bone for years.

The panel voted 17 to 6 in favor of recommending extra labeling data about the medications’ long term efficacy and safety.

The FDA (Food and Drug Administration) usually goes along with the Panel’s recommendations, but it does not have to.

The FDA announced on September 7th in a preliminary review of the drugs that “(unusual fractures) appear to have a strong association with bisphosphonates, although causality has not been determined. There is no agreement on the extent to which cumulative use of bisphosphonates increases the risk of atypical fractures.”

FDA researchers concluded that there is no clear evidence of benefit or harm for women who continue taking bisphosphonates for over five years, and “no subset of patients who have a clear and consistent reduced fracture risk.”

The current label states that all efficacy and safety clinical trial data on bisphosphonates are based on one to four years usage, depending on the medication, and that nobody yet knows what the optimal use duration is.

Panel members said it is difficult to know in advance which patients might benefit from long-term bisphosphonates usage.

The majority of patients who gave evidence to the Panel regarding their unusual femur fractures said they had started on bisphosphonates in their 50s or 60s. Some said they were treated for osteopenia, meaning they did not have osteoporosis at the start of treatment, but their bone density was lower than it should be.

Panel member, Lewis Nelson, director of medical toxicology fellowship program at New York University, said that the updated label for the drugs should state clearly that efficacy drops off after some time, possibly five years.

The FDA said that in July 2011 it was also looking at conflicting studies coming from the UK on bisphosphonates pills, such as Actonel, Fosamax and Boniva, with regards to esophageal cancer risk.

In 2010 global sales of Actonel reached $1.03 billion, Bonica $975 million, Fosamax $926 million and Reclast $579 million.