Flibanserin is a non-hormonal, multifunctional serotonin agonist and antagonist (MSAA) approved for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. It represents a significant advancement in the neuropharmacological management of this condition, targeting central neurotransmitter pathways involved in sexual motivation. Unlike hormonal therapies, flibanserin works by modulating serotonin, dopamine, and norepinephrine systems to rebalance neural circuits governing sexual desire. Its approval marked a pivotal shift toward evidence-based, centrally-acting treatment options for this often-overlooked aspect of women’s health.

Features

• Active ingredient: Flibanserin 100 mg
• Pharmacologic class: Multifunctional serotonin agonist and antagonist (MSAA)
• Mechanism of action: 5-HT1A receptor agonist and 5-HT2A receptor antagonist
• Additional activity: Moderate agonist activity at dopamine D4 receptors
• Formulation: Oral tablet
• Prescription status: Schedule-controlled substance (C-IV)
• Manufacturer: Original developer: Boehringer Ingelheim; currently marketed by various license holders
• Regulatory status: FDA-approved for premenopausal women with HSDD

Benefits

• Increases the number of satisfying sexual events (SSEs) per month
• Reduces distress associated with low sexual desire
• Improves sexual desire scores as measured by validated patient-reported outcomes
• Non-hormonal mechanism avoids systemic endocrine effects
• Targeted central nervous system action addresses the neurobiological basis of desire
• May improve overall sexual well-being and relationship satisfaction

Common use

Flibanserin is specifically indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD). HSDD is characterized by a persistent deficiency or absence of sexual fantasies and desire for sexual activity that causes marked distress or interpersonal difficulty, and which is not better accounted for by another medical or psychiatric condition, relationship problems, or the effects of a medication or substance. The “acquired” specification denotes that the low desire developed in a patient who previously had no problems with sexual interest, while “generalized” indicates that it is not situational or partner-specific.

Clinical trials have demonstrated efficacy in women who meet strict diagnostic criteria for HSDD, particularly those who experience significant distress related to their low desire. It is not indicated for use in postmenopausal women or men, nor is it approved for treating sexual dysfunction due to comorbid medical or psychiatric conditions, relationship issues, or substance use.

Dosage and direction

The recommended dosage is 100 mg taken orally once daily at bedtime. Administration at bedtime is crucial to mitigate the risk of hypotension, syncope, and central nervous system depression, as these adverse reactions are more likely to occur shortly after ingestion.

Treatment should be initiated and monitored by a healthcare provider experienced in diagnosing and managing HSDD. The tablet should be swallowed whole and not crushed or chewed. It may be taken with or without food, though consistent administration relative to meals is recommended.

Patients should be advised that clinical improvement in sexual desire and distress may not be apparent for several weeks. Clinical trials demonstrated significant separation from placebo at 4 weeks, with continued improvement through 24 weeks of treatment. Discontinuation should be considered if no meaningful benefit is observed after 8 weeks of therapy.

Precautions

Flibanserin carries several important safety considerations requiring careful patient selection and monitoring:

Hypotension and Syncope: Flibanserin can cause significant hypotension and syncope, particularly with concomitant alcohol use. The risk is increased during the first two weeks of treatment and when starting therapy after interruption. Patients should be thoroughly counseled about alcohol avoidance.

Central Nervous System Depression: Flibanserin may cause CNS depression (somnolence, sedation). Patients should not engage in potentially hazardous activities until they know how flibanserin affects them, particularly when starting treatment or increasing dosage.

Hepatic Impairment: Flibanserin is contraindicated in patients with hepatic impairment due to significantly increased exposure and risk of adverse reactions. Baseline liver function tests should be considered.

Concomitant Medications: Flibanserin is metabolized primarily by CYP3A4 and to a lesser extent by CYP2C19. Strong or moderate CYP3A4 inhibitors are contraindicated. Concomitant use with other CNS depressants increases the risk of hypotension, syncope, and CNS depression.

Pregnancy and Lactation: There are no adequate data on developmental risks associated with use in pregnant women. Animal studies showed adverse effects on development at exposures greater than those used clinically. Use during pregnancy only if potential benefit justifies potential risk. It is not known whether flibanserin is excreted in human milk; caution should be exercised when administered to nursing women.

Contraindications

• Hepatic impairment
• Concomitant use with strong or moderate CYP3A4 inhibitors
• Concomitant use with CYP2C19 inhibitors in poor metabolizers
• History of hypersensitivity to flibanserin or any component of the formulation
• Concomitant alcohol use (absolute contraindication)

Strong CYP3A4 inhibitors include drugs such as ketoconazole, itraconazole, clarithromycin, ritonavir, and conivaptan. Moderate inhibitors include erythromycin, diltiazem, verapamil, fluconazole, and grapefruit juice.

Possible side effect

The most common adverse reactions (occurring in ≥2% of patients and more frequently than with placebo) include:

Very common (≥10%):

• Dizziness (11.4%)
• Somnolence (11.2%)
• Nausea (10.9%)

Common (2-10%):

• Fatigue (9.2%)
• Insomnia (4.6%)
• Dry mouth (3.2%)
• Anxiety (2.1%)

Serious but less common adverse effects:

• Syncope (0.4%)
• Hypotension (1.0%)
• Accidental injury (2.3%)

The incidence of syncope and hypotension increases significantly with alcohol consumption. In clinical trials, syncope occurred in 0.1% of patients without alcohol but up to 4% when alcohol was consumed within close proximity to flibanserin dosing.

Most adverse reactions are mild to moderate in severity and often diminish with continued treatment. Dose reduction to 50 mg daily may be considered for patients who cannot tolerate the 100 mg dose due to side effects.

Drug interaction

Flibanserin has multiple clinically significant drug interactions:

CYP3A4 Inhibitors (Contraindicated): Strong and moderate CYP3A4 inhibitors significantly increase flibanserin exposure. Concomitant use is contraindicated. A washout period of at least 2 weeks should occur before starting flibanserin after discontinuation of these inhibitors.

CYP2C19 Inhibitors: In poor metabolizers of CYP2C19, concomitant use with CYP2C19 inhibitors may increase flibanserin exposure. Use should be avoided in these patients.

Alcohol: Concomitant use dramatically increases the risk of hypotension, syncope, and CNS depression. Patients must completely avoid alcohol during treatment.

CNS Depressants: May potentiate sedation and hypotension when used with other CNS depressants including benzodiazepines, opioids, antipsychotics, antidepressants, and sedative antihistamines.

Oral Contraceptives: Flibanserin may decrease the effectiveness of hormonal contraceptives. Additional non-hormonal contraception should be used during treatment.

Other Serotonergic Drugs: Theoretical risk of serotonin syndrome when combined with other serotonergic agents, though this was not observed in clinical trials.

Missed dose

If a dose is missed at the usual bedtime, the patient should skip the missed dose and take the next dose at the regular time the following evening. Patients should not take two doses within the same 24-hour period, as this may increase the risk of adverse effects including hypotension and syncope.

Consistent nightly administration is important for maintaining therapeutic effect. Patients should be advised to establish a routine for taking flibanserin to minimize the likelihood of missed doses.

Overdose

There is limited experience with flibanserin overdose in humans. Based on its pharmacological profile, symptoms of overdose would be expected to include exaggerated pharmacological effects: severe hypotension, profound sedation, and possibly syncope.

In cases of suspected overdose, supportive care is the mainstay of treatment. This includes continuous hemodynamic monitoring, ECG monitoring, and symptomatic treatment of hypotension with intravenous fluids. Vasopressors may be required for refractory hypotension. Patients should be monitored for at least 24 hours due to the drug’s half-life of approximately 11 hours.

Gastric lavage or administration of activated charcoal may be considered if presented soon after ingestion, though the clinical benefit is uncertain. There is no specific antidote for flibanserin overdose.

Storage

Store at room temperature (20-25°C or 68-77°F), with excursions permitted between 15-30°C (59-86°F). Keep in the original container to protect from moisture and light. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging.

Proper disposal of unused medication is important to prevent accidental ingestion or misuse. Patients should be advised to utilize drug take-back programs or follow specific disposal instructions provided with the medication.

Disclaimer

Flibanserin is available by prescription only and should be used under the supervision of a qualified healthcare provider. This information is for educational purposes only and does not replace professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or treatment.

The full prescribing information, including boxed warning regarding hypotension, syncope, and CNS depression with alcohol use, should be reviewed before initiating therapy. Patients must be enrolled in the FDA-approved Risk Evaluation and Mitigation Strategy (REMS) program to receive flibanserin.

Reviews

Clinical trials demonstrated statistically significant improvements in satisfying sexual events (SSE) and sexual desire with flibanserin compared to placebo. In integrated study results, flibanserin-treated women experienced approximately 0.5-1.0 additional SSEs per month and significant improvements on the Female Sexual Function Index (FSFI) desire domain and the Female Sexual Distress Scale-Revised (FSDS-R).

Patient-reported outcomes suggest that women who respond to flibanserin experience meaningful improvements in desire and reduced distress associated with low sexual desire. However, the effect size is modest, and not all patients respond. The benefit-risk profile must be carefully considered for each individual.

Real-world evidence continues to accumulate regarding flibanserin’s effectiveness and safety in clinical practice. Many experts emphasize the importance of comprehensive evaluation and management of HSDD, including psychological and relationship factors, rather than relying solely on pharmacological intervention.