Updated 8/19/2015 with FDA approval

The FDA has approved Sprout Pharmaceuticals’ flibanserin (Addyi), the first treatment for female sexual dysfunction.
 
Hypoactive sexual desire disorder (HSDD) is estimated to affect 7.7% to 14% of premenopausal women in the United States, or 5.5 to 8.6 million individuals.
 
FDA panels previously rejected new drug applications for the HSDD treatment in September 2013 and February 2014. But Sprout returned with additional data on the drug, leading to a favorable FDA panel opinion on June 4, 2015.

Some have described the pink pill as a female counterpart to the erectile dysfunction drug, sildenafil (Viagra).
 
Addyi is contraindicated in patients with liver impairment and those on moderate or strong CYP3A4 inhibitors, and the treatment carries a Boxed Warning about the risks of severe hypotension and loss of consciousness among those who drink alcohol. Because of this, Addyi will only be available via certified health care professionals and certified pharmacies.
 
Addyi was also approved with a risk evaluation and mitigation strategy (REMS) because of the risk of severe hypotension and loss of consciousness. Prescribers of Addyi must be certified with the REMS program and complete training. They must also use a Patient-Provider Agreement form to emphasize the risks of drinking while taking Addyi.
 
Pharmacies must only provide Addyi if the patient has a prescription form from a certified prescriber, and pharmacists are responsible for also counseling patients prior to dispensing about the importance of alcohol abstinence.
 
Mechanism of action
 
The exact mechanism of action in HSDD treatment is unknown, though it does have known mixed agonist/antagonist effects on postsynaptic serotonergic receptors. Specifically, flibanserin is a 5-hydroxytryptamine (5-HT)1A agonist and a 5-HT2A antagonist. Prior to its proposed use in women with HSDD, the drug was considered for an antidepressant indication.
 
Although all antidepressants carry a black-box warning for potentially increasing suicidality risk, further study revealed no sign of this increased risk in patients taking flibanserin.
 
Pharmacokinetic profile
 
Although peak levels of flibanserin are typically reached within 45 to 60 minutes of administration, taking the medication with a meal may delay peak levels by 1 to 3 hours. The terminal elimination half-life is approximately 12 hours.
 
Taking flibanserin with a high-fat, high-calorie meal increases exposure by more than 50%. Coadministration with the strong CYP3A4 inhibitors ketoconazole and fluconazole increased exposure 4.5-fold and 7-fold, respectively.
 
Although hormonal contraceptives are weak inhibitors of CYP3A4, these medications increase exposure to flibanserin by approximately 40%.
 
Efficacy data
 
In 3 clinical trials, each of which were approximately 6 months in duration, researchers identified statistically significant improvements in the number of satisfying sexual events, as well as reduced distress levels related to sexual desire. To measure the latter, investigators used a survey known as the Female Sexual Function Index (FSFI).
 
From a baseline median of 2 to 3 satisfying sexual events each month, daily use of flibanserin increased levels by a median of 0.5 to 1 event per month over placebo treatment. On the sexual desire score, which ranges from 1.2 to 6, baseline mean levels of 1.8 to 1.9 increased by a mean of 0.3 to 0.4 points more than treatment with placebo, although sexual desire score improvements were not consistently statistically significant.
 
On the FSFI, which ranges from 0 to 4, baseline mean levels of 3.2 to 3.4 were reduced by an average of 0.3 to 0.4 more points in women receiving active treatment than in women receiving placebo.
 
Dosing and potential interactions
 
Proposed flibanserin dosing is 100 mg taken daily at bedtime.
 
Common adverse events associated with the drug include hypotension, syncope, and accidental injury. Investigators also identified a potentially greater incidence of appendicitis in women taking flibanserin.
 
Flibanserin use with hormonal contraceptives increased the incidence of somnolence, dizziness, and fatigue, while use with triptans increased the incidence of somnolence and upper respiratory infection.
 
Genotoxicity and reproductive data
 
Use of flibanserin in mice led to increased rates of mammary tumors in female animals. However, genotoxicity assays do not indicate potential for DNA damage. Additionally, the mechanism of tumor induction in animals is unknown.
 
Because premenopausal women would primarily use flibanserin, reproductive safety data are particularly important. Pregnancy testing was required for women entering clinical trials of flibanserin, and women who became pregnant discontinued treatment. Effects on pregnant animal models were not discussed in an FDA briefing document regarding the drug.