On September 9, 2011 two independent advisory panels to the Food and Drug Administration (FDA) recommended limiting the use of bone-building drugs called bisphosphonates to only five years. Bisphosphonates are used by over 5 million women in the United States and include the drugs Aclasta, Actonel, Altevia, Boniva, Fosamax, and Reclast.
The medical advisers did not press the issue as strongly as the FDA staff itself did in a 45-page report issued in previously. The staff report said studies “suggest no significant advantage of continuing drug therapy beyond five years.” The FDA is expected to issue a revised label in November for the drugs Aclasta, Actonel, Altevia, Boniva, Fosamax, and Reclast.
The two panels met jointly to comment on the staff’s broad safety review of the drugs, prompted by concerns over a relatively small number of long-term users who had suffered unusual thigh fractures or a serious jaw disease. The benefits of the drugs have only been proven for three to five years, not longer, FDA staff members said, warning about links to those rare conditions after longer use.
The advisory meeting ended in a 17-6 vote on a single question put to the panel for a vote: whether the labels should “further clarify the duration of use” of the drugs. Several advisers said the question was vague. So are the current labels, which say, “The optimal duration of use has not been determined.”
The FDA said an estimated 9 percent of users take the drugs longer than three years, and under 1 percent take them longer than five years. But none of the panel members recommended firm restrictions on longer-term use. None suggested a black box warning, as some former patients who suffered the injuries are seeking.
Dr. Lewis S. Nelson, a toxicologist with the New York University School of Medicine and chairman of the FDA Drug Safety and Risk Management Committee said the evidence warranted “something a little bit more dramatic,” like moving the statement to the “warnings” section of the label from the section on “indications and usage.”
The six people who voted against a label change said there was insufficient evidence of risk in longer use, especially with a drug proven to benefit women for the first three to five years.
The committee also called for more study of the overall effectiveness of the drugs in their desired goal of preventing fractures. And the advisers recommended that the FDA take a close look at why the drugs are prescribed as preventive medicine for women who do not even have osteoporosis.
Panelists noted that it’s difficult to predict which women will benefit from long-term bisphosphonate use. The Fosamax study did find that women’s bone mineral density at the time they discontinued the drug was strongly related to their fracture risk over the next five years.
Data from a 10-year Merck clinical trial show that Fosamax’s benefits outweigh its potential hazards in osteoporosis patients who are at risk for regular bone fractures, said Arthur Santora, executive director of clinical research at Merck Research Laboratories.
Temporary cessation of Fosamax treatment, known as a drug holiday, “may be considered for patients who are no longer considered to have a sufficiently high fracture risk,” Santora told the panel. “However, neither restricting the duration of use nor implementing a drug holiday is likely to be beneficial for patients at sufficiently high fracture risk who require long-term treatment.”