Flibanserin (brand name Addyi) is indicated for the treatment of “hypoactive sexual desire disorder” (HSDD) in premenopausal women. It is the first drug to be approved by the FDA for female sexual dysfunction. Flibanserin acts on central serotonin receptors and was initially developed to be an antidepressant. Although it was not effective for depression, flibanserin did appear to increase sex drive.
The use of flibanserin is limited by modest efficacy and the risk of severe hypotension and syncope (fainting). This risk is increased by alcohol, and by medications that inhibit CYP3A4 (the primary enzyme that metabolizes flibanserin). Consequently, alcohol use is contraindicated during flibanserin therapy, and flibanserin is contraindicated in individuals taking moderate or strong CYP3A4 inhibitors, which include several antibiotics, antiviral agents, cardiac drugs, and grapefruit juice.
The CYP2C19 enzyme also contributes to the metabolism of flibanserin, and individuals who lack CYP2C19 activity (“CYP2C19 poor metabolizers”) have a higher exposure to flibanserin than normal metabolizers.
The risk of hypotension, syncope, and CNS depression may be increased in individuals who are CYP2C19 poor metabolizers, according to the FDA-approved drug label, which also states that approximately 2–5% of Caucasians and Africans and 2–15% of Asians are CYP2C19 poor metabolizers. However, the drug label does not provide alternative dosing for poor metabolizers (Table 1). The standard recommended dosage of flibanserin is 100 mg once per day, taken at bedtime (1).