Apparently, the third time is the charm for flibanserin, a combination 5-HT1A agonist/5-HT2A antagonist treatment for female hypoactive sexual desire (HSD), part of the newly designated FSIAD or female sexual interest/arousal disorder.
The Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee met together to discuss the medication’s fate on June 4. This third application was submitted for the more restrictive indication of use in premenopausal women, and adds more clinical data to the three published registration studies. The committees agreed that treatment results in only modest improvement, and does have significant side effects, but should be approved with several requirements: a risk-management plan to address serious side effects, a requirement for physician certification, and postmarketing studies to further evaluate safety and efficacy long-term and in women who drink alcohol.
The side effects were rare, but could be serious, such as hypotension, sedation, and syncope. These effects could be made worse with alcohol or concurrent use of CYPA34-inhibitor medications, found in some common medications such as several antibiotics, antifungals, and antidepressants. Citing a dearth of treatment options for women with FSIAD, the Food and Drug Administration advisory panel voted 18-6 that the overall benefit-risk profile of flibanserin was positive and recommended approval. The full FDA decision is expected by August 2015.
As women’s physicians, ob.gyns. are strategically placed to have the biggest effect in the war on female sexual interest/arousal disorder or FSIAD. Not only are we the physicians women most commonly see during the reproductive years, we already have developed a rapport and built a trust to discuss embarrassing topics such as vaginal odors, urinary and fecal incontinence, and sexually transmitted infections. Talking about sex is a logical extension of our roles, and should be a top priority, should flibanserin finally be approved.
Although we are trained to talk about sex, a significant proportion of ob.gyns. either don’t or don’t feel comfortable doing so. And when we talk about sex, we tend to gloss over it superficially. For instance, nearly 40% of women admit to having some form of sexual dysfunction ( Obstet. Gynecol. 2008;112:970-8 ). Nearly two-thirds of doctors ask about sexual activity, but only 40% inquire about sexual problems or dysfunction. Just 28% routinely ask about sexual orientation, and only 29% of doctors ask patients whether their sex life is satisfying ( J. Sex. Med. 2012;9:1285-94 ).
And why do physicians not ask? “I don’t feel like I have anything to offer them,” is a common refrain.
Flibanserin has been touted in the lay media as the “female Viagra.” But not only is the mechanism of action different, so is the efficacy. The effectiveness of flibanserin in its three registration studies only improved the number of satisfying sexual events (SSEs) per month by about one, compared with placebo. And in two of the three studies, “quality-of-life” questionnaire ‘Female Sexual Dysfunction Index’ scores after treatment were not significantly higher. Having 8-12 more SSEs per year does not sound like much, but to those affected by FSIAD, this could more than double the number of events those women are having per year. In short, although flibanserin does not work for everyone, for some, it does.
Women’s groups have been praising the possibility of approving the first medication that helps with FSIAD, especially since there are a plethora of medications that have been approved for male sexual interest and arousal. However, the potential side effects are not minimal, and a full discussion of the risks and benefits should be done with one’s physician before making a decision to try any medication. That being said, rates of sedation and syncope (9%-11% and 0.4%) are lower than the rates for similar psychoactive medications (Wellbutrin, Paxil, Cymbalta, Zoloft, Prozac, Celexa).
I think that it is laudable that the FDA wants to be so careful with a medication that could potentially be prescribed very frequently upon initial launch, since it will be the first and only medication in the class. However, even a medication with a very low side-effect profile can have large absolute numbers of complications if it is widely used. Nobody in the medical community wants to see the medication introduced, only to be withdrawn from the market when large numbers of side effects are reported. And we certainly don’t cherish the idea of a new wave of class-action lawsuit advertisements. However, the goal of a modest return of libido is just as laudable, and I hope the FDA agrees.
Patrick J. Woodman, D.O., is a urogynecologist and clinical professor at Michigan State University College of Osteopathic Medicine in East Lansing, and Obstetrics & Gynecology Residency Program Director at St. John Macomb-Oakland Hospital, St. John Providence Health System in Warren, Mich. He reported having no relevant financial disclosures. Email him at obnews@frontlinemedcom.com.
