The U.S. Food and Drug Administration (FDA) has approved Addyi (flibanserin, Sprout Pharmaceuticals) to boost sexual desire in premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), according to an agency press release.
Addyi is now the first FDA-approved treatment for HSDD, which is characterized by low sexual desire that causes significant distress or interpersonal difficulty and is not related to a co-existing medical or psychiatric condition, problems within a relationship or the effects of a medication or other drug substance.
The disorder is acquired when a patient who previously had no problems begins to develop issues with sexual desire. HSDD is considered generalized when it occurs regardless of the type of sexual activity, the situation or the sexual partner.
Addyi is a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, although it remains unclear through which mechanism the drug improves sexual desire and related distress.
The drug is a once-daily treatment that is to be taken at bedtime to reduce the risk for adverse events due to possible hypotension, syncope and central nervous system depression like sleepiness and sedation. If no improvement in sexual desire or related distress is experienced after 8 weeks, women should discontinue treatment, according to the release.
Researchers assessed the efficacy of the 100-mg bedtime dose of Addyi in three 24-week randomized, double-blind, placebo-controlled trials that involved about 2,400 premenopausal women (mean age, 36 years) with acquired, generalized HSDD. Duration of the disorder was approximately 5 years.
In the trials, women tracked the number of satisfying sexual events (scored on a range of 1.2 to 6.0), reported sexual desire during the preceding 4 weeks and distress due to low sexual desire (range of 0 to 4). Treatment with Addyi appeared to increase the number of satisfying sexual events by 0.5 to one additional event per month, increased sexual desire score by 0.3 to 0.4 and decreased related distress by 0.3 to 0.4, as compared with placebo, according to information in the release.
Results from additional analyses in women who felt much or very much improved overall with treatment showed that 10% more patients who took Addyi vs. placebo experienced meaningful improvements in satisfying sexual events, sexual desire or distress. The drug, however, is not linked to enhanced sexual performance.
Dizziness, sleepiness, nausea, fatigue, insomnia and dry mouth were the most commonly reported adverse reactions associated with use of Addyi.
In clinical trials of women with acquired, generalized HSDD, about 3,000 women have received the 100-mg bedtime dose of Addyi, with about 1,700 receiving treatment for at least 6 months and 850 receiving treatment for at least 1 year.
The release warns that Addyi can cause hypotension and syncope, and drinking alcohol or taking Addyi with certain medicines, including moderate or strong CYP3A4 inhibitors, can exacerbate the risk for these severe adverse events.
The drug is also being approved with a risk evaluation and mitigation strategy (REMS) that includes elements to assure safe use (ETASU). The REMS is required by the FDA due to the increased risk for severe hypotension and syncope due to the interaction between Addyi and alcohol.
Addyi also carries a Boxed Warning emphasizing the severe hypotension and syncope risks in those who drink alcohol during treatment or those who use moderate or strong CYP3A4 inhibitors as well as those who have liver impairment. The FDA is requiring the manufacturer to conduct three studies to better understand these risks.
“Today’s approval provides women distressed by their low sexual desire with an approved treatment option. The FDA strives to protect and advance the health of women, and we are committed to supporting the development of safe and effective treatments for female sexual dysfunction,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research (CDER), said in the release.
“Because of a potentially serious interaction with alcohol, treatment with Addyi will only be available through certified health care professionals and certified pharmacies. Patients and prescribers should fully understand the risks associated with the use of Addyi before considering treatment.”