{Sexual Dysfunction}

FLIBANSERIN

BLACK BOX WARNINGS: Hypotension, syncope risk due to EtOH, CYP3A4 inhibitors, hepatic impairment

Adult Dosing

• Hypoactive sexual desire disorder (HSDD)
  • 100 mg PO qHS
  • D/C if no improvement in 8 weeks
• Moderate-strong CYP3A4 inhibitor use
  • Initiate 2 weeks after last dose of CYP3A4 inhibitor
  • Initiate CYP3A4 inhibitor 2 days after last dose
  • Do not use concomitantly (see DI)
• Administration
  • Missed doses administered at next bedtime

Pediatric Dosing

• Not indicated for pediatric use

Renal and Hepatic Dosing

• Renal
  • Manufacturer provides no specific dosage recommendations
• Hepatic
  • Any degree of impairment: contraindicated
  • Poor CYP2C19 metabolizers: increase monitoring for ADRs

Contraindications & Cautions

• Contraindications
  • Hypersensitivity
  • Concomitant moderate-strong CYP3A4 inhibitors
  • Hepatic impairment
• Cautions
  • FDA Black Box warnings
    • Increased risk of severe hypotension and syncope with:
      • EtOH: wait ≥2 hrs after consuming ≤2 drinks; if >2 drinks consumed, skip dose
      • Do not consume EtOH until next day after dose taken
      • CYP3A4 inhibitors: moderate or strong contraindicated (see adult dosing for separation protocol)
      • Monitor closely with multiple weak inhibitors
      • Hepatic impairment: significant increase observed with any degree of impairment
  • May cause CNS depression; risk increased if taken during waking hrs or concomitant EtOH/CNS depressants
  • Evidence of mammary tumors in animal testing; clinical significance of these findings unknown

Indications & Uses

• Acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women
• Limitations of use:
• Not for HSDD due to co-existing psychiatric or medical condition, relationship issues, or caused by other medications/substances

Mechanism of Action

• Therapeutic mechanism unknown; agonist activity at 5-HT1A and antagonist activity at 5-HT2A

Adverse Drug Reactions

• ≥2%
  • dizziness (11.4%)
  • dry mouth (2.4%)
  • fatigue (9.2%)
  • insomnia (4.9%)
  • nausea (10.4%)
  • somnolence (11.2%)
• <2%
  • abdominal pain (1.5%)
  • accidental injury (2.7%)
  • anxiety (1.8%)
  • appendicitis (0.2%)
  • constipation (1.6%)
  • metrorrhagia (1.4%)
  • rash (1.3%)
  • sedation (1.3%)
  • vertigo (1%)

Pregnancy and Lactation

• Pregnancy
  • Risk Summary: fetal risk cannot be ruled out; weigh risk/benefit
  • Human Data: No data
  • Animal Data: fetal toxicity occurred only in presence of significant maternal toxicity
• Lactation
  • Risk Summary: likely present in human milk; possible risk of serious ADRs in exposed infants
  • Effect on production: No data
  • Minimizing exposure: breastfeeding not recommended with Tx

Kinetics/Dynamics

• Bioavailability: 33%
• Peak Plasma Time: 0.75 hrs
• Protein-Bound: 98%
• Half-life: 11 hrs
• Metabolism: Primarily by CYP3A4, lesser CYP2C19
  • Minimally by CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2D6
• Excretion
  • Urine (44%)
  • Feces (51%)

Overdose Management

• Symptomatic and supportive

Interactions

• Go to Drug Interactions [DI]

Trade Names

• Dosing Strengths: (tablet) 100 mg

* = Discontinued

• United States: Addyi
• Canada: Addyi

Other Information

• Class: Sexual Dysfunction
• Requires prescription
• ATC Code: G02CX02

References

1. ASHP Drug Compendium (Flibanserin (Systemic); Central Nervous System Agents, Miscellaneous)
2. FDA Monograph flibanserin (Addyi) https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022526s009lbl.pdf (Accessed November 2020)
3. Health Canada Monograph flibanserin (Addyi) https://pdf.hres.ca/dpd_pm/00044049.PDF

Contributor(s)

1. Reiner, Stefan, PharmD

Updated/Reviewed: November, 2020