Flibanserin

Approved Indications:

• Hypoactive Sexual Desire Disorder (HSDD) in Premenopausal Women: Treatment of acquired, generalized hypoactive sexual desire disorder (HSDD), characterized by low sexual desire causing marked distress or interpersonal difficulty, not due to a co-existing medical or psychiatric condition, problems within the relationship, or effects of a medication or substance.

Off-label / Clinically Accepted Uses:

• Use in postmenopausal women is not approved and lacks sufficient evidence.
• Investigational use in other female sexual dysfunctions remains under study.

• Adults (Premenopausal Women):
• Recommended dose is 100 mg orally once daily at bedtime.
• Initiate treatment only in premenopausal women diagnosed with HSDD.
• Continuous daily dosing is required to maintain effect.
• Pediatrics:
• Safety and efficacy have not been established; not recommended.
• Elderly:
• Use with caution; limited data available.
• Hepatic Impairment:
• Contraindicated in moderate to severe hepatic impairment due to increased exposure.
• Renal Impairment:
• No dose adjustment generally required for mild to moderate impairment; limited data in severe impairment.
• Administration:
• Take orally once daily at bedtime to reduce risk of hypotension and syncope.
• Duration:
• Evaluate effectiveness after 8 weeks; discontinue if no improvement.

Flibanserin is a multifunctional serotonin receptor modulator that acts as a 5-HT1A receptor agonist and 5-HT2A receptor antagonist in the central nervous system. This dual action decreases inhibitory serotonergic activity and enhances dopaminergic and noradrenergic neurotransmission in brain regions involved in sexual desire regulation. By modulating these neurotransmitters, flibanserin improves sexual desire and reduces distress associated with low sexual desire.

• Absorption:
  Rapidly absorbed with peak plasma concentrations reached approximately 45 to 60 minutes after oral administration.
• Bioavailability:
  Oral bioavailability is moderate; food intake increases absorption but also delays peak concentration.
• Distribution:
  Extensive tissue distribution; approximately 98% protein bound.
• Metabolism:
  Primarily metabolized in the liver by CYP3A4 and to a lesser extent CYP2C19 enzymes into inactive metabolites.
• Elimination:
  Half-life is approximately 11 hours. Excreted mainly via feces and urine.

• Pregnancy:
  FDA Category C. Animal studies have shown adverse effects on the fetus at high doses; no adequate human data. Use only if clearly needed.
• Lactation:
  Unknown if excreted in human milk. Caution is advised; breastfeeding is generally not recommended during treatment.

• Primary class: Female sexual dysfunction agent
• Subclass: Serotonin receptor modulator

• Known hypersensitivity to flibanserin or any excipients
• Use with alcohol due to risk of severe hypotension and syncope
• Concurrent use with moderate or strong CYP3A4 inhibitors (e.g., ketoconazole, erythromycin)
• Hepatic impairment (moderate to severe)
• Pregnancy and breastfeeding

• Severe Hypotension and Syncope: Risk increased with alcohol and CYP3A4 inhibitors; patients must abstain from alcohol during treatment and for at least 2 weeks after discontinuation.
• Central Nervous System Effects: Somnolence, fatigue, dizziness, and potential for CNS depression.
• Risk of Depression and Suicidal Ideation: Use cautiously in patients with depression history; monitor closely.
• Interactions with CYP3A4 Inhibitors: Can significantly increase flibanserin levels, leading to toxicity.
• Monitoring: Regular assessment of blood pressure, mental status, and symptom improvement is necessary.

Common Adverse Effects:

• Dizziness
• Somnolence
• Nausea
• Fatigue
• Insomnia
• Dry mouth

Serious/Rare Side Effects:

• Syncope and hypotension, especially with alcohol use
• Depression exacerbation or suicidal ideation
• Rare allergic reactions

• Alcohol: Contraindicated; combination may cause severe hypotension and syncope.
• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): Increase flibanserin plasma levels and toxicity risk; contraindicated.
• CYP3A4 inducers (e.g., rifampin): May reduce flibanserin efficacy by lowering plasma levels.
• CNS depressants: Additive sedative effects; caution advised.
• Other serotonergic drugs: Potential risk of serotonin syndrome; monitor closely.

• Updated labeling emphasizes strict contraindication with alcohol use due to hypotension risk.
• FDA guidelines restrict use to premenopausal women only; postmenopausal safety and efficacy not established.
• Monitoring for psychiatric symptoms is highlighted due to risk of depression.
• Ongoing evaluation of long-term safety is recommended.

• Store at room temperature between 20°C and 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original packaging until use.
• Keep out of reach of children.
• No refrigeration required.