March 6, 2013 -- An FDA panel has rejected two nonhormonal options for the treatment of moderate to severe hot flashes resulting from menopause.
Although all panel members agreed that nonhormonal treatments are needed to relieve the hot flashes that make life difficult for many postmenopausal women, they decided to say no to Sefelsa (gabapentin) and low-dose Pexeva (paroxetine mesylate).
If either drug were approved by the FDA, it would be the first nonhormonal drugs for hot flashes on the market. Gabapentin is an antiseizure medication. Paroxetine mesylate is being offered as a low-dose version of the antidepressant Pexeva. Both drugs have been used "off-label" by doctors to help women with hot flashes.
The panel voted 12-2 against Sefelsa, saying they were unimpressed by the drug's limited effectiveness in controlling hot flashes in light of its possible mental health side effects and other central nervous system effects.
Kathryn M. Curtis, PhD, from the CDC, calls Sefelsa's effect "limited and modest" in explaining her no vote.
"We all understand the huge need for a nonhormonal treatment for [hot flashes], but approving a drug that has a very modest effect is almost misleading to those women who are really looking for something that is very effective," Curtis says.
Valerie Montgomery Rice, MD, from Morehouse School of Medicine in Atlanta, echoes her sentiments.
"As much as I would love to have nonhormonal alternatives for women, I'm concerned about the sustainability and the limited [effectiveness] of this product. I'm also concerned about the dizziness and disorientation with this drug. We just have to keep trying," she says.
Linda Keyes, a consumer representative on the panel and one of the two yes voters, says the demand and desire for such nonhormonal treatment "is high enough that I feel that a very modest reduction is still acceptable, assuming the risks are known and carefully watched, which I believe they can be."
Keyes says women are very aware of the risks with Sefelsa. "It's all over the Internet. While I don't think that's a justification for approval, I do think it might be a reason for increased guidance and regulation. It might be better just putting gabapentin out there."
Later in the day, the panel voted 10-4 against low-dose Pexeva, saying the drug's minimal benefit did not outweigh its risks.
A few concerns also were raised about the drug's safety profile, and in particular its association with suicidal thoughts and osteoporosis.
Julia V. Johnson, MD, from the University of Massachusetts Medical School in Worcester, who was chairperson of the day's committee meeting, says she felt those risks were small and did not appear to be different from the risks seen with more standard doses of paroxetine. "Still, we have very little information about this lower dose. We did see some effect on suicidal ideation, and I was somewhat concerned that there may be a greater effect than seen."
A bigger stumbling block for the panel was the relatively small benefit seen with Pexeva compared with a placebo. "I voted against recommending approval when I looked at the magnitude of the treatment effect relative to the magnitude of the placebo effect, where there is no risk involved," says Daniel L. Gillen, PhD, from the University of California, Irvine.
However, some panel members believe they saw some evidence of benefit with the drug.
"I'm not worried about the safety profile, because it's already an FDA-approved drug. If we are worried, the way to address that is to help women access a lower-dose version," says Eleanor Bimla Schwarz, MD, from the University of Pittsburgh School of Medicine in Pennsylvania.
Richard Bockman, MD, PhD, from the Hospital for Special Surgery in New York City, says it is time to approve this drug because it is already being commonly used off-label to treat hot flashes.
"I think there is a very small beneficial effect from this drug," he says, explaining his yes vote. "It is widely used and there is wide experience with this drug. This very small dose is probably safe. I think it's time to legitimize its use."
Clifford J. Rosen, MD, from Maine Medical Center Research Institute in Scarborough, voted against recommending approval but says he empathizes with the yes voters.
"In some ways, having an indication might allow us to have better surveillance over who is getting this drug and how it is being utilized. Right now, we have very strong difficulty figuring this out," he says.
The FDA is expected to make a decision on Sefelsa by May 31 and on low-dose Pexeva by June 28. The agency does not have to follow the advice of its advisory committees, but it usually does.
To see a version of this story for physicians, visit Medscape, the leading site for physicians and health care professionals.