Gabapentine deemed ineffective for hot flashes.
SILVER SPRING, MD. -- Women need a nonhormonal treatment for moderate to severe vasomotor symptoms in menopause. But gabapentin is not that drug, according to the majority of a Food and Drug Administration advisory panel, who recommended against approval of a sustained-release formulation of the antiepileptic drug on March 3.
At the meeting, the FDA's Reproductive Health Drugs Advisory Committee voted 12-2 that the risk-benefit profile of gabapentin did not support approval of the proposed indication, citing the limited, modest effect on vasomotor symptoms in three clinical trials. Also working against recommendation of approval were the known risks of the medication, particularly effects on cognition and other central nervous system effects. The sustained-release formulation, manufactured by Depomed, stays in the stomach for 8-10 hours, prolonging release of the drug. Were it to be approved despite the panel's recommendation, it would be the first nonhormonal drug approved for treating vasomotor symptoms. The manufacturer recommends that the drug be dosed by titration to a total daily dose of 1,800 mg, with a 600-mg dose taken with the morning meal and 1,200 mg taken with the evening meal.
"We all recognize the critical need for nonhormonal medications [for vasomotor symptoms], and our patients have clearly been asking for such a product," said the panel chair Julia Johnson, professor and chair of the department of obstetrics and gynecology, University of Massachusetts, Worcester. "However, the risk of the medication cannot be ignored for a treatment with marginal effectiveness on hot flashes and gabapentin's adverse event profile, she noted.
Another panelist, Kathryn Curtis, Ph.D., in the Centers for Disease Control and Prevention's division of reproductive health, said that despite the "huge" need for a nonhormonal treatment for vasomotor symptoms, the drug had a very limited, modest effect and its approval would be "misleading" to women who need the treatment.
Depomed conducted three phase III studies of postmenopausal women (mean ages 53-54 years), who had at least 7 moderate to severe hot flashes per day or at least 50 per week during the previous 30 days. The studies compared gabapentin with placebo. There was a statistically significant difference in the frequency of hot flashes among those treated with 1,800 mg/day, compared with those on placebo at week 4, but not at week 12, in all three studies. Changes from baseline in the severity of hot flashes were statistically significant at week 4 in all three studies and remained statistically significant in two of the three studies at week 12. But while statically significant, the benefits over placebo were modest.
The most common adverse events associated with treatment were dizziness and vertigo, and somnolence and sedation, as expected.
Gabapentin is widely prescribed off-label for vasomotor symptoms. The Depomed formulation was approved in 2011 for postherpetic neuralgia and is marketed as Gralise for this indication. The labeling includes a warning about suicidality risk, a class labeling for antiepileptic drugs.
The immediate-release formulation of gabapentin (Neurontin) was first approved in 1993 as an adjunctive treatment of partial seizures, and has been used off label for vasomotor symptoms. Gabapentin encarbil, a prodrug of gabapentin, marketed as Horizant, was approved in 2011 for restless legs syndrome and postherpetic neuralgia.
The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting.
Occasionally, a panelist may be given a waiver, but not at this meeting.
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|Publication:||Family Practice News|
|Article Type:||Conference news|
|Date:||Mar 15, 2013|
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