Addyi (Flibanserin): Current Use and Recommendations
Addyi (flibanserin 100 mg) is FDA-approved for treating acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, taken once daily at bedtime. 1
Indication
Flibanserin is specifically indicated for premenopausal women experiencing HSDD—characterized by persistently low sexual desire that causes marked distress and is not attributable to other medical conditions, relationship problems, or medication side effects. 2
Dosing Recommendations
- Standard dose: 100 mg once daily at bedtime 1
- Timing is critical: Must be taken at bedtime to minimize risks of hypotension and syncope 1
- Trial period: Discontinue after 8 weeks if no benefit is observed 3
- Missed dose: If a dose is missed at bedtime, take the next dose at bedtime the following day; do not take during waking hours 1
Efficacy Profile
Clinical trials demonstrate modest but statistically significant improvements:
- Approximately 0.5-1 additional satisfying sexual event per month compared to placebo 4
- Improvements in sexual desire scores (FSFI desire domain increase of 0.27-0.32) 4, 5
- Reduction in sexual distress 5
The effect size is modest, with meta-analyses showing standardized mean differences of 0.32-0.59 for primary outcomes. 4, 6 Women's global impression scores indicated "minimal improvement to no change" in some analyses. 4
Critical Safety Considerations
Boxed Warning: Alcohol Interaction
Contraindicated with alcohol use due to severe hypotension and syncope risk. 1 However, recent real-world studies show:
- Moderate alcohol (2 units of wine) consumed 2.5 hours before bedtime dosing was well-tolerated without clinically significant hypotension or syncope 7
- Morning dosing studies showed increased adverse events with alcohol, but bedtime dosing appears safer 8
- Clinical caveat: Despite these findings, the FDA boxed warning remains in effect and should guide prescribing 1
Common Adverse Events
- Dizziness (11.4%) - 4-fold increased risk vs placebo 4
- Somnolence (11.2%) - 4-fold increased risk 4
- Nausea (10.4%) - 2.4-fold increased risk 4
- Fatigue (9.2%) 3
- Discontinuation rate: 2.2-fold higher than placebo due to adverse events 4
Contraindications
- Hepatic impairment - contraindicated due to increased hypotension/syncope risk 1
- Concurrent moderate or strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) - significantly increases flibanserin levels and adverse event risk 1
- Alcohol use - per boxed warning 1
Special Populations and Limitations
Cancer Patients
Important limitation: Flibanserin has not been evaluated in women with cancer or those on endocrine therapy, and the risk/benefit ratio remains uncertain in this population. 2 The 2018 ASCO guidelines state that clinicians may offer flibanserin to premenopausal women with HSDD, but emphasize this caveat. 2
CYP2C19 Poor Metabolizers
These patients have increased flibanserin exposure and may experience more adverse events. 1
Clinical Implementation Algorithm
- Confirm HSDD diagnosis: Low sexual desire causing distress, not explained by other factors
- Screen for contraindications: Hepatic disease, CYP3A4 inhibitor use, alcohol consumption patterns
- Counsel on bedtime dosing requirement and alcohol avoidance
- Set expectations: Modest benefit (approximately 0.5 additional satisfying sexual events/month)
- Reassess at 8 weeks: Discontinue if no benefit
- Monitor for adverse events: Particularly dizziness, somnolence, hypotension
Context Within Treatment Paradigm
Psychosocial counseling should be offered as first-line or adjunctive therapy for women with HSDD, as recommended by ASCO guidelines. 2 Flibanserin represents a pharmacological option within a broader biopsychosocial treatment approach, not a standalone solution. 9
The medication's modest efficacy, significant adverse event profile, and multiple contraindications require careful patient selection and shared decision-making about whether the potential benefits justify the risks and costs.