What is Flibanserin (Addyi)?

What is Flibanserin (Addyi)?

Flibanserin is an FDA-approved oral medication (100 mg taken once daily at bedtime) specifically indicated for treating acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. 1

Mechanism of Action

• The exact mechanism by which flibanserin treats HSDD is not fully understood 1
• Flibanserin acts as a serotonin 5-HT1A receptor agonist and 5-HT2A receptor antagonist, with additional moderate antagonist activity at 5-HT2B, 5-HT2C, and dopamine D4 receptors 1

Clinical Efficacy

• Flibanserin results in approximately 1 additional satisfying sexual event every 2 months compared to placebo 2, 3
• The medication demonstrates statistically significant improvements in sexual desire as measured by the Female Sexual Function Index (FSFI) desire domain score 2
• In pooled analysis of pivotal trials, flibanserin showed a mean increase of 2.1 satisfying sexual events over 28 days versus 1.2 with placebo (p < 0.0001) 4
• Flibanserin also significantly reduces distress related to low sexual desire compared to placebo 4

Dosing and Administration

• The recommended dose is 100 mg taken once daily at bedtime 1
• Steady-state plasma concentrations are achieved after 3 days of dosing 1
• Food increases the extent of absorption (AUC increased 1.18- to 1.56-fold depending on fat content), though the clinical significance is modest 1

Common Adverse Effects

• The most frequent adverse events (occurring in ≥10% of patients) include dizziness and somnolence 4
• These sedation-related effects are the primary reason for bedtime dosing 5
• The medication is generally well-tolerated with no withdrawal reactions observed upon discontinuation 6

Critical Safety Warnings and Contraindications

• Flibanserin is absolutely contraindicated in patients with any degree of hepatic impairment, as exposure increases 4.5-fold, significantly raising the risk of hypotension, syncope, and CNS depression 1
• Alcohol consumption is contraindicated due to increased risk of hypotension and syncope 1
• The medication carries a boxed warning regarding these risks 1
• CYP2C19 poor metabolizers (2-15% of various populations) require increased monitoring for adverse reactions, particularly hypotension, due to increased drug exposure 1

Drug Metabolism and Interactions

• Flibanserin is primarily metabolized by CYP3A4 and, to a lesser extent, by CYP2C19 1
• Strong or moderate CYP3A4 inhibitors would be expected to significantly increase flibanserin exposure and should be avoided 1
• Approximately 98% of flibanserin is bound to human serum proteins, mainly albumin 1

Special Populations and Limitations

• Flibanserin has NOT been evaluated in women with a history of cancer or those on endocrine therapy, and the risk/benefit ratio in these populations remains uncertain 2
• The medication is not indicated for use in postmenopausal women, pediatric patients, or geriatric patients 1
• Breastfeeding is not recommended during treatment due to potential for serious adverse reactions including sedation in breastfed infants 1
• Safety and effectiveness data in cancer survivors or postmenopausal women is limited 3

Clinical Context and Treatment Positioning

• The American College of Obstetricians and Gynecologists recommends flibanserin as a first-line FDA-approved medication for premenopausal women with HSDD, with bremelanotide as an alternative 3
• While the efficacy is modest (approximately one additional satisfying sexual event every two months), it represents the first FDA-approved pharmacological option for this condition 3
• Off-label alternatives with limited data include bupropion and buspirone 3