Flibanserin represents a significant pharmacological development in the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Unlike therapies that focus solely on hormonal modulation, flibanserin is a multifunctional serotonin agonist and antagonist (MSAA) that targets central neurochemical pathways implicated in sexual motivation and response. Its approval marked the first non-hormonal, centrally-acting agent specifically indicated for this distressing and often overlooked condition, offering a novel mechanism of action for clinicians. This product card provides a comprehensive, evidence-based overview for healthcare professionals.

Features

• Active Ingredient: Flibanserin
• Pharmacologic Class: Multifunctional Serotonin Agonist and Antagonist (MSAA)
• Available Dosage Form: 100 mg oral tablets
• Mechanism of Action: Acts as a postsynaptic 5-HT1A receptor agonist and a presynaptic 5-HT2A receptor antagonist, modulating serotonin, dopamine, and norepinephrine activity in key brain regions such as the prefrontal cortex.
• FDA Indication: For the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD).
• Prescription Status: Available only through a certified Risk Evaluation and Mitigation Strategy (REMS) program due to the risk of severe hypotension and syncope, particularly with alcohol interaction.

Benefits

• Addresses the core symptom of HSDD by increasing the number of satisfying sexual events (SSEs) per month, as demonstrated in pivotal clinical trials.
• Targets the underlying neurobiological imbalance associated with low sexual desire, rather than providing only symptomatic or hormonal support.
• Offers a non-hormonal treatment option, which is a critical consideration for women with contraindications to or concerns about estrogen-based therapies.
• Improves patient-reported outcomes, including scores on the Female Sexual Function Index (FSFI) desire domain and the Female Sexual Distress Scale-Revised (FSDS-R) Item 13, which measures distress related to low desire.
• Provides a daily oral dosing regimen that integrates into a patient’s routine, promoting adherence outside of the sexual context.

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 or recurrent deficiency (or absence) of sexual fantasies and desire for sexual activity, which causes marked distress or interpersonal difficulty, and is not better accounted for by a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance. The “acquired” specifier denotes that the low desire developed in a patient who previously had no such concerns, while “generalized” applies to the lack of desire that is not situational or partner-specific. It is not intended for use in postmenopausal women or men, and it is not indicated to enhance sexual performance.

Dosage and direction

• Recommended Dosage: 100 mg taken orally once daily at bedtime.
• Administration: The tablet should be swallowed whole. Administration at bedtime is mandated to mitigate the risk of adverse events such as hypotension, syncope, somnolence, and sedation.
• Initiation and Titration: Treatment should be initiated and prescribed only by certified healthcare providers enrolled in the REMS program. The starting dose is 100 mg; no titration is required.
• Timing of Effect: Patients should be counseled that a clinical response may not be observed for at least 8 weeks of continued use. Efficacy was established in 24-week trials.
• Re-evaluation: The need for continued treatment should be reassessed after 8 weeks to determine if the benefits outweigh the risks for the individual patient.

Precautions

• Hypotension and Syncope: Flibanserin can cause severe hypotension and syncope. The risk is increased with concomitant alcohol use, concomitant use with moderate or strong CYP3A4 inhibitors, and in patients with hepatic impairment.
• Central Nervous System Depression: Flibanserin can cause central nervous system (CNS) depression (e.g., somnolence, sedation). Patients should not engage in potentially hazardous activities requiring full alertness, such as driving, until at least 6 hours after taking the dose and they know how the drug affects them.
• Alcohol Interaction: Concomitant use of alcohol with flibanserin is contraindicated. Even small amounts of alcohol can precipitate severe hypotension and syncope. Patients must be advised to abstain from alcohol completely.
• Hepatic Impairment: Flibanserin is contraindicated in patients with hepatic impairment. It is extensively metabolized by the liver, and impairment significantly increases drug exposure and the associated risks.
• Pregnancy and Lactation: There are no adequate data on the developmental risk associated with the use of flibanserin in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if flibanserin is present in human milk; a risk to the breastfed infant cannot be ruled out.

Contraindications

• Concomitant use with alcohol.
• Concomitant use with moderate or strong CYP3A4 inhibitors (e.g., ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice).
• Hepatic impairment.
• Concomitant use with other CNS depressants (this is a strong warning, though not an absolute contraindication in the labeling, extreme caution is required).

Possible side effect

The most common adverse reactions (≥2% incidence and greater than placebo) observed in clinical trials include:

• Dizziness
• Somnolence (sleepiness)
• Nausea
• Fatigue
• Insomnia
• Dry mouth
• Other reported side effects include: anxiety, flushing, abdominal pain, constipation, paresthesia (tingling sensation), and rash.

The most serious adverse reactions are syncope (fainting) and hypotension (low blood pressure), particularly when associated with alcohol use.

Drug interaction

Flibanserin is primarily metabolized by the cytochrome P450 enzyme CYP3A4 and, to a lesser extent, by CYP2C19. Its pharmacokinetics are highly susceptible to drug interactions.

• Strong and Moderate CYP3A4 Inhibitors (CONTRAINDICATED): Concomitant use dramatically increases flibanserin exposure, leading to a high risk of severe hypotension and syncope. Examples include: ketoconazole, itraconazole, voriconazole, clarithromycin, erythromycin, nefazodone, diltiazem, verapamil, grapefruit juice.
• Weak CYP3A4 Inhibitors: May increase flibanserin concentration. Use with caution and monitor for adverse reactions. Examples include: oral contraceptives, cimetidine.
• CYP2C19 Inhibitors (e.g., fluconazole, fluvoxamine, ticlopidine): May increase flibanserin concentration. Use with caution.
• CNS Depressants: Concomitant use with other CNS depressants (e.g., benzodiazepines, narcotics, antipsychotics, antidepressants, sedating antihistamines) may potentiate sedation and hypotension.
• P-gp Inhibitors (e.g., verapamil): May increase flibanserin absorption.

Missed dose

If a dose is missed, the patient should skip that dose and take the next dose at the usual time the following night. The patient should not double the dose to make up for a missed one.

Overdose

• Manifestations: In cases of overdose, the expected clinical effects would be an exaggeration of the known adverse reactions, most notably severe hypotension, syncope, and profound CNS depression (sedation, somnolence).
• Management: There is no specific antidote for flibanserin overdose. Management should consist of supportive measures, including continuous ECG and vital sign monitoring. Due to the high protein binding of flibanserin, dialysis is unlikely to be effective. The patient’s airway should be maintained, and intravenous fluids and vasopressors may be required to treat hypotension.

Storage

• Store flibanserin tablets at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
• Keep in the original bottle to protect from light and moisture.
• Keep out of reach of children and pets.

Disclaimer

This information is intended for educational purposes of healthcare professionals and is a summary of key prescribing information. It is not exhaustive. The prescriber must be certified in the flibanserin REMS program and must consult the full FDA-approved Prescribing Information, including the Boxed Warning, prior to initiating therapy. The healthcare provider is responsible for thoroughly evaluating the patient, discussing the significant risks (especially regarding alcohol), benefits, and alternatives, and ensuring the patient is an appropriate candidate for this medication.

Reviews

• Clinical Trial Data: Pooled data from three 24-week, randomized, placebo-controlled trials (N= approximately 2,400 premenopausal women with HSDD) showed that flibanserin 100 mg daily resulted in a statistically significant increase from baseline in the number of satisfying sexual events (SSEs) per month (an increase of 0.8 to 1.2 over placebo) and a significant decrease in distress scores related to sexual desire (FSDS-R Item 13 score decreased 0.3 to 0.4 over placebo).
• Expert Opinion (Medical Literature): Reviews in journals like Fertility and Sterility and JAMA acknowledge flibanserin as a first-in-class treatment with a novel mechanism for a condition with few options. However, experts consistently emphasize its modest efficacy and significant safety profile, concluding that it represents an option for a carefully selected subset of patients who understand the risks and strictly adhere to contraindications, particularly alcohol avoidance.
• Patient Reported Outcomes: While some women in clinical trials and post-marketing reports have noted a meaningful improvement in desire and a reduction in associated distress, others have discontinued use due to side effects (notably dizziness, nausea, and fatigue) or a lack of perceived benefit.