General Information

Addyi (flibanserin) is a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist.

Addyi is specifically indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty.

Dosing/Administration

Addyi is supplied as a tablet for oral administration.

The recommended dosage is 100 mg taken once daily at bedtime. Addyi should be dosed at bedtime because administration during waking hours increases risks of hypotension, syncope, accidental injury, and central nervous system (CNS) depression.

Discontinue treatment after 8 weeks if no improvement is observed.

Side Effects

Adverse effects associated with the use of Addyi may include, but are not limited to, the following:

dizziness

somnolence

nausea

fatigue

insomnia

dry mouth

The Addyi drug label comes with a Black Box Warning:

The use of Addyi and alcohol together close in time increases the risk of severe hypotension and syncope. Patients should wait at least two hours after consuming one or two standard alcoholic drinks before taking Addyi at bedtime or to skip their Addyi dose if they have consumed three or more standard alcoholic drinks that evening.

Severe hypotension and syncope can occur when Addyi is used with moderate or strong CYP3A4 inhibitors or in patients with hepatic impairment; therefore, Addyi use in these settings is contraindicated.

Clinical Trial Results

The FDA approval of Addyi was based on three 24- week, randomized, double-blind, placebo-controlled trials (Studies 1, 2, and 3). The three trials included premenopausal women with acquired, generalized HSDD of at least 6 months duration. In the clinical trials, acquired HSDD was defined as HSDD that developed in subjects who previously had no problems with sexual desire. Generalized HSDD was defined as HSDD that was not limited to certain types of stimulation, situations or partners. The subjects were treated with Addyi 100 mg once daily at bedtime (n = 1187) or placebo (n = 1188). These trials each had two co-primary efficacy endpoints, one for satisfying sexual events (SSEs) and the other for sexual desire:

The change from baseline to Week 24 in the number of monthly SSEs (i.e., sexual intercourse, oral sex, masturbation, or genital stimulation by the partner). The SSEs were based on patient responses to the following questions: “Did you have a sexual event?” and “Was the sex satisfying for you?”

Studies 1 and 2 had a different sexual desire endpoint than Study 3:

In Studies 1 and 2, the sexual desire co-primary endpoint was the change from baseline to Week 24 in the calculated monthly sexual desire score and was based on patient responses to the question: “Indicate your most intense level of sexual desire.” Every day, patients rated their sexual desire level from 0 (no desire) to 3 (strong desire) and recorded their response in an electronic Diary (eDiary). These responses were summed over a 28-day period to yield the calculated monthly sexual desire score, which ranged from 0 to 84.

In Study 3, the desire domain of the Female Sexual Function Index (FSFI Desire) was the sexual desire co-primary endpoint. The desire domain of the FSFI has two questions. The first question asks patients “Over the past 4 weeks, how often did you feel sexual desire or interest?”, with responses ranging from 1 (almost never or never) to 5 (almost always or always). The second question asks patients “Over the past 4 weeks, how would you rate your level (degree) of sexual desire or interest?”, with responses ranging from 1 (very low or none at all) to 5 (very high). The FSFI Desire score was calculated by adding the patient’s responses to these two questions then multiplying that sum by 0.6. The FSFI Desire domain score ranged from 1.2 to 6.

In all three trials, Addyi resulted in statistically significant improvement compared to placebo in the change from baseline in monthly SSEs at Week 24. In Study 1 and 2, there were no statistically significant differences between Addyi and placebo for the eDiary sexual desire endpoint (change in baseline to Week 24). In contrast, in Study 3 there was statistically significant improvement in the change from baseline to Week 24 in sexual desire (using the FSFI Desire Domain) with Addyi compared to placebo.