Flibanserin (Addyi) for Hypoactive Sexual Desire Disorder
Recommended Treatment and Dosage
For premenopausal women with acquired, generalized HSDD, flibanserin 100 mg taken once daily at bedtime is the recommended first-line FDA-approved pharmacological treatment. 1, 2
Dosing Specifications
- Standard dose: 100 mg orally once daily at bedtime 1, 2
- Must be taken at bedtime because daytime administration significantly increases risks of hypotension, syncope, accidental injury, and CNS depression 2
- Discontinue after 8 weeks if no improvement is observed 2
Expected Clinical Outcomes
The efficacy of flibanserin is modest but statistically significant:
- Approximately 1 additional satisfying sexual event every 2 months compared to placebo 1, 3
- Statistically significant improvements in FSFI desire domain scores (mean increase of 0.9 vs 0.6 for placebo) 4
- Significant reduction in sexual distress measured by FSDS-R-13 scores 4, 5
- In pooled analysis of 2,465 women, mean increase in satisfying sexual events was 2.1 vs 1.2 for placebo over 28 days 4
Critical Safety Warnings and Contraindications
Absolute Contraindications
- Moderate or strong CYP3A4 inhibitors (severe hypotension and syncope risk) 2
- Any degree of hepatic impairment 2
- Hypersensitivity reactions 2
Alcohol Interaction (Boxed Warning)
- Patients must wait at least 2 hours after consuming 1-2 standard alcoholic drinks before taking flibanserin at bedtime 2
- Skip the dose entirely if 3 or more alcoholic drinks consumed that evening 2
- Avoid alcohol until the following day after taking bedtime dose 2
- Combined use dramatically increases risk of severe hypotension and syncope 2
Common Adverse Effects
The most frequently reported adverse events (≥2% incidence):
- Dizziness (10.5-10.8%) 2, 4, 5
- Somnolence (11.8%) 2, 4, 6
- Nausea 2, 5
- Fatigue (10.3%) 2, 6
- Insomnia 2
- Dry mouth 2
Discontinuation due to adverse events occurred in 9.6% of flibanserin-treated women vs 3.7% on placebo 5
Important Drug Interactions
- Oral contraceptives and other weak CYP3A4 inhibitors: Increase flibanserin exposure and adverse reaction incidence 2
- Strong CYP2C19 inhibitors: Increase flibanserin exposure, raising risk of hypotension, syncope, and CNS depression 2
- CYP3A4 inducers: Not recommended; substantially reduce flibanserin concentrations 2
- Digoxin: Flibanserin increases digoxin concentrations; requires increased monitoring for digoxin toxicity 2
Special Population Considerations
CYP2C19 Poor Metabolizers
- Increased flibanserin exposure with heightened risk of hypotension, syncope, and CNS depression 2
Postmenopausal Women
- FDA approval is specifically for premenopausal women only 2
- Off-label use in postmenopausal women showed efficacy in FSFI desire domain scores but not consistently in satisfying sexual events 7
- Consider alternative FDA-approved options like bremelanotide or off-label treatments 1, 8
Cancer Survivors
- Flibanserin has NOT been evaluated in women with cancer history or those on endocrine therapy 3
- Risk/benefit ratio remains uncertain in this population 3
Nursing Mothers
- Not recommended 2
Patient Counseling Points
- Avoid activities requiring full alertness (operating machinery, driving) until at least 6 hours after each dose and until effects are known 2
- Patients experiencing pre-syncope symptoms should immediately lie supine and seek medical help if symptoms don't resolve 2
- Treatment is not indicated for enhancing sexual performance 2
- HSDD must be acquired and generalized, not due to co-existing medical/psychiatric conditions, relationship problems, or medication effects 2
Alternative First-Line Option
Bremelanotide is an FDA-approved alternative for premenopausal women with HSDD, administered as a self-injected subcutaneous dose as needed (melanocortin receptor agonist mechanism) 1