What is the recommended treatment for hypoactive sexual desire disorder (HSDD) with Flibanserin (Addyi)?

Flibanserin (Addyi) for Hypoactive Sexual Desire Disorder

Recommended Treatment Approach

Flibanserin 100 mg taken once daily at bedtime is the FDA-approved first-line pharmacological treatment for premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), though its clinical benefit is modest—approximately one additional satisfying sexual event every 2 months compared to placebo. 1, 2, 3

Patient Selection Criteria

Before prescribing flibanserin, confirm the following diagnostic criteria are met:

• Premenopausal status (flibanserin is FDA-approved only for premenopausal women, though evidence suggests potential efficacy in postmenopausal women) 2, 4
• Acquired, generalized HSDD characterized by low sexual desire causing marked distress or interpersonal difficulty 2
• Exclusion of other causes: Low desire is NOT due to co-existing medical/psychiatric conditions, relationship problems, or effects of other medications 2
• Duration assessment: The pooled trial population had mean HSDD duration of 56.5 months 3

Dosing and Administration

Critical dosing requirements:

• 100 mg once daily at bedtime ONLY 2, 5
• Never take during waking hours—this significantly increases risks of hypotension, syncope, accidental injury, and CNS depression 2
• Discontinue after 8 weeks if no improvement 2, 6

Absolute Contraindications

Do not prescribe flibanserin if the patient has:

• Hepatic impairment of any degree 2
• Concurrent use of moderate or strong CYP3A4 inhibitors, including:
  • HIV protease inhibitors (ritonavir, atazanavir, indinavir, etc.) 2
  • Oral azole antifungals (fluconazole, ketoconazole, itraconazole, posaconazole) 2
  • Macrolide antibiotics (erythromycin, clarithromycin) 2
  • Calcium channel blockers (diltiazem, verapamil) 2
  • Nefazodone 2

Critical Safety Warnings

Alcohol Interaction (Boxed Warning)

Patients must avoid alcohol completely from the time of dosing until the following day: 2

• If consuming 1-2 standard drinks, wait at least 2 hours before taking flibanserin at bedtime 2
• If consuming 3+ standard drinks, skip that evening's dose entirely 2
• Alcohol combined with flibanserin dramatically increases risk of severe hypotension and syncope 2

Common Adverse Events

The most frequent side effects include:

• Dizziness (11.4-11.8%) 3, 6, 7
• Somnolence (11.2%) 3, 6, 7
• Nausea (10.4%) 6, 7
• Fatigue (9.2-10.3%) 5, 6, 7
• Insomnia (4.9%) 6

Risk ratios compared to placebo: dizziness 4.00, somnolence 3.97, nausea 2.35, fatigue 1.64 7

Expected Clinical Outcomes

Set realistic expectations with patients:

• Mean increase of 0.49 additional satisfying sexual events per month (approximately 1 additional event every 2 months) 7
• FSFI desire domain score improvement of 0.27-0.9 points 3, 7
• Reduction in sexual distress as measured by FSDS-R scores 3, 5
• Women's global impression indicated minimal improvement to no change on average 7

Special Populations and Considerations

Cancer Survivors

• Flibanserin has NOT been studied in women with cancer history or those on endocrine therapy 8
• The American Society of Clinical Oncology notes the risk/benefit ratio is uncertain in this population 8
• Consider alternative approaches first (psychosexual counseling, mechanical devices) 8, 1

Postmenopausal Women

• Not FDA-approved for postmenopausal women 2
• Evidence from the PLUMERIA trial suggests potential efficacy, though one primary endpoint (satisfying sexual events) did not reach statistical significance 4
• FSFI desire domain scores did show significant improvement in postmenopausal women 4

Drug Interactions

• Weak CYP3A4 inhibitors (including oral contraceptives) increase flibanserin exposure and adverse event risk 2
• Strong CYP2C19 inhibitors increase flibanserin exposure 2
• CYP3A4 inducers substantially reduce flibanserin concentrations—use not recommended 2
• Digoxin: Flibanserin increases digoxin levels; monitor digoxin concentrations closely 2
• CYP2C19 poor metabolizers have increased flibanserin exposure and higher risk of adverse events 2

Patient Counseling Points

Instruct patients to:

• Lie down immediately if experiencing lightheadedness or dizziness 2
• Seek emergency help if pre-syncope symptoms persist or if they feel they might faint 2
• Avoid activities requiring full alertness (driving, operating machinery) for at least 6 hours after dosing 2
• Not breastfeed while taking flibanserin 2
• Report all new medications or supplements before starting them 2

Alternative Treatment Options

When flibanserin is contraindicated or not tolerated, consider:

• Bremelanotide (FDA-approved alternative for premenopausal HSDD, subcutaneous injection as needed) 1, 9
• Off-label bupropion (limited safety/efficacy data) 1
• Psychosexual counseling (recommended by ASCO as first-line for cancer survivors) 8
• Mechanical devices (vibrators, clitoral stimulatory devices) 1
• Pelvic physical therapy 1

Common Pitfalls to Avoid

• Do not prescribe for performance enhancement—flibanserin is not indicated for this purpose 2
• Do not prescribe without excluding situational or relationship-based causes of low desire 2
• Do not continue beyond 8 weeks without documented benefit 2, 6
• Do not minimize the alcohol interaction—this is a boxed warning with serious consequences 2
• Do not prescribe to patients with any degree of hepatic impairment 2