What is Addyi (flibanserin) and how is it used to treat hypoactive sexual desire disorder in premenopausal women?

What is Addyi (Flibanserin)?

Addyi (flibanserin) is an FDA-approved oral medication specifically indicated for treating acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women—characterized by persistently low sexual desire that causes marked distress and is not due to medical/psychiatric conditions, relationship problems, or other medications. 1

Mechanism and Pharmacology

Flibanserin works as a 5-HT1A receptor agonist and 5-HT2A receptor antagonist, modulating serotonergic pathways in the brain that influence sexual desire 2, 3. This distinguishes it fundamentally from medications like sildenafil (Viagra), which work peripherally on blood flow—flibanserin acts centrally on neurotransmitter systems.

Clinical Efficacy

The medication produces modest but statistically significant improvements in sexual function 4:

• Approximately 0.5 to 1 additional satisfying sexual event per month compared to placebo 4, 2
• Improved sexual desire scores on validated instruments (Female Sexual Function Index desire domain and electronic diary assessments) 2, 3
• Reduced sexual distress associated with HSDD 2

Meta-analyses consistently demonstrate these benefits across diverse patient populations, though the magnitude of effect is considered moderate 4, 5.

Dosing and Administration

Critical dosing requirements 1:

• 100 mg once daily at bedtime only
• Must not be taken at any other time of day due to increased risk of hypotension and syncope
• Takes daily administration (not on-demand like erectile dysfunction medications)

Safety Profile and Contraindications

Absolute Contraindications 1:

Do not prescribe flibanserin if patients:

• Have liver problems
• Use alcohol (must abstain from alcohol after bedtime dose until the following day)
• Take moderate or strong CYP3A4 inhibitors, including:
  • HIV protease inhibitors (ritonavir, atazanavir, indinavir, nelfinavir, saquinavir)
  • Azole antifungals (fluconazole, ketoconazole, itraconazole, posaconazole)
  • Macrolide antibiotics (erythromycin, clarithromycin)
  • Calcium channel blockers (diltiazem, verapamil)
  • Hepatitis C antivirals (boceprevir, telaprevir)
  • Nefazodone

Common Adverse Effects 4, 2:

The most frequent side effects include:

• Dizziness (4-fold increased risk vs placebo)
• Somnolence (4-fold increased risk)
• Nausea (2.4-fold increased risk)
• Fatigue (1.6-fold increased risk)

Risk of discontinuation due to adverse events is 2.2 times higher than placebo 4.

Black Box Warning 1:

Severe hypotension and syncope risk is significantly increased with:

• Concurrent alcohol use
• CYP3A4 inhibitor co-administration
• Hepatic impairment

Patients experiencing presyncope or lightheadedness should lie down immediately and seek emergency care if symptoms persist.

Clinical Context and Guidelines

Guideline Recommendations:

ASCO (2018) states that clinicians may offer flibanserin to premenopausal women experiencing HSDD, with important caveats 6:

• Has not been evaluated in women with cancer history or those on endocrine therapy
• Risk/benefit ratio remains uncertain in these populations

NCCN (2024) recommends flibanserin as a reasonable option for premenopausal survivors with low desire/libido/intimacy issues 7, noting:

• Preliminary data suggest potential efficacy in breast cancer survivors on endocrine therapy 7
• May also have efficacy in postmenopausal women, though not FDA-approved for this indication 7

Important Clinical Caveats:

1. Not for postmenopausal women (FDA indication is premenopausal only) 1
2. Not for enhancing sexual performance—specifically treats HSDD 1
3. Not studied in men 1
4. Quality of evidence is graded as "very low" in systematic reviews 4
5. Patient global impression scores indicate "minimal improvement to no change" 4

Patient Selection Algorithm

Appropriate candidates:

• Premenopausal women
• Acquired, generalized HSDD (developed after previously normal desire; occurs regardless of partner/situation)
• Significant distress from low desire
• No medical/psychiatric cause, relationship problems, or medication effects
• No liver disease
• Willing to abstain from alcohol
• Not taking CYP3A4 inhibitors
• Realistic expectations about modest benefit

Counsel patients that:

• Benefits are modest (approximately 1 additional satisfying sexual event every 2 months)
• Daily medication required (not on-demand)
• Side effects are common, particularly dizziness and somnolence
• Must avoid alcohol completely while on treatment
• Should not drive or operate machinery within 6 hours of dosing 1

Breastfeeding

Advise patients not to breastfeed while taking flibanserin, as it is unknown whether the drug passes into breast milk 1.