Flibanserin represents a significant pharmacological development in the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. It is the first and only non-hormonal, centrally-acting agent approved by the FDA specifically for this indication. This product card provides a comprehensive, expert-level overview of its pharmacology, clinical application, and safety profile for healthcare professionals.

Features

• Mechanism of Action: Multifunctional serotonin receptor agonist and antagonist; acts as a full agonist on postsynaptic 5-HT1A receptors and an antagonist on 5-HT2A receptors.
• Pharmacokinetics: Rapidly absorbed with a mean absolute oral bioavailability of approximately 33%; high plasma protein binding (>98%).
• Formulation: Standardized 100 mg oral tablet.
• Metabolism: Primarily hepatic, via CYP3A4 and CYP2C19 pathways, with minor contributions from glucuronidation.
• Elimination: Mean terminal half-life of approximately 11 hours; excreted predominantly in urine (44%) and feces (51%).
• Onset of Action: Therapeutic effects on sexual desire are typically observed after 4-8 weeks of consistent dosing.

Benefits

• Targeted Neurotransmitter Modulation: Specifically addresses the neurochemical imbalance (decreased dopamine/norepinephrine, increased serotonin) theorized to underlie HSDD.
• Non-Hormonal Profile: Offers a treatment option for women who cannot or prefer not to use hormonal therapies, mitigating associated risks.
• Improvement in Sexually-Related Distress: Clinical trials demonstrated statistically significant reductions in distress scores related to low sexual desire, a core diagnostic criterion.
• Increase in Satisfying Sexual Events (SSEs): Leads to a measurable increase in the number of SSEs per month compared to placebo.
• Disease-Specific Indication: The first agent developed and approved specifically for premenopausal women with HSDD, validating the condition and its treatment.

Common use

Flibanserin is 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 which 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 it developed in a patient who previously had no problems with sexual desire, and “generalized” specifies that it is not situational. It is not intended for use in postmenopausal women or men, and its efficacy for treating sexual dysfunction due to other medical conditions or relationship issues has not been established.

Dosage and direction

The recommended dosage is 100 mg taken orally once daily at bedtime.

Administration Instructions:

• Timing: Administration at bedtime is mandated to mitigate the risk of severe hypotension and syncope, which are associated with the drug’s mechanism and are more likely to occur if the patient is upright.
• Consumption: The tablet should be swallowed whole; it can be taken with or without food. However, patients should avoid grapefruit or grapefruit juice as it inhibits CYP3A4 and can significantly increase flibanserin exposure.
• Initiation: Prescribing should be initiated by a healthcare provider familiar with the diagnosis of HSDD and the risks of flibanserin.
• REMS Program: Prescribers and pharmacies must be certified through the FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) program due to the risks of hypotension and syncope.

Treatment efficacy should be reassessed after 8 weeks of continuous therapy. Discontinuation should be considered if no meaningful improvement in desire and associated distress is observed.

Precautions

• Hypotension and Syncope: There is a significant risk of sudden hypotension and loss of consciousness (syncope). This risk is increased with alcohol consumption, hepatic impairment, and concomitant use of moderate or strong CYP3A4 inhibitors. Patients must be advised of the strict alcohol contraindication.
• Central Nervous System Depression: Can cause somnolence, sedation, and fatigue. Patients should exercise caution when engaging in activities requiring full alertness, such as driving or operating machinery, until they know how the drug affects them.
• Hepatic Impairment: Contraindicated in patients with hepatic impairment due to substantially increased exposure and amplified risk of adverse effects, including hypotension and syncope.
• Pregnancy and Lactation: Not recommended for use during pregnancy. Safety during lactation is unknown; a risk-benefit analysis is required.
• Alcohol Use: ABSOLUTE CONTRAINDICATION. Even small amounts of alcohol can precipitate severe hypotension and syncope. Patients must commit to complete abstinence from alcohol.

Contraindications

1. Concomitant use with alcohol.
2. Concomitant use with moderate or strong CYP3A4 inhibitors (e.g., ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice).
3. Hepatic impairment.
4. Use in patients taking other central nervous system depressants (e.g., benzodiazepines, narcotics, sleep aids) is not recommended due to additive sedative effects.

Possible side effect

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

• Very Common (≥10%): Dizziness, somnolence (sleepiness), nausea.
• Common (2-10%): Fatigue, insomnia, dry mouth, anxiety, hypotension, syncope (fainting).

Other notable side effects can include:

• Abdominal pain
• Constipation
• Rash
• Paresthesia (tingling sensation)

The most serious side effects are syncope and hypotension, which necessitate immediate medical attention.

Drug interaction

Flibanserin is primarily metabolized by CYP3A4 and, to a lesser extent, CYP2C19. It is a weak inhibitor of P-glycoprotein (P-gp) and BCRP.

• Strong/Moderate CYP3A4 Inhibitors (CONTRAINDICATED): Concomitant use dramatically increases flibanserin plasma concentrations, elevating the risk of severe hypotension, syncope, and CNS depression. Examples include: ketoconazole, itraconazole, voriconazole, clarithromycin, diltiazem, verapamil, grapefruit juice.
• CYP2C19 Inhibitors: May increase flibanserin exposure. Use with caution and monitor for adverse reactions. Examples include: proton pump inhibitors (e.g., omeprazole), fluconazole.
• CNS Depressants: Additive sedative effects are likely. Use with extreme caution. Examples include: benzodiazepines, opioids, antipsychotics, antidepressants, sedative antihistamines, alcohol (CONTRAINDICATED).
• Other Serotonergic Drugs: The theoretical risk of serotonin syndrome exists. Use with caution with other serotonergic agents (e.g., SSRIs, SNRIs, triptans).
• P-gp/BCRP Substrates: Flibanserin may increase concentrations of drugs that are substrates of these transporters (e.g., digoxin, rosuvastatin). Monitor accordingly.

Missed dose

If a dose is missed at the scheduled bedtime, the patient should skip that dose entirely. The missed dose should not be taken the following morning. Taking a dose in the morning increases the risk of hypotension, syncope, and CNS depression during waking hours when the patient is upright and active. The patient should simply resume the regular 100 mg dose at bedtime the next evening. Patients should not double the dose to make up for a missed one.

Overdose

Symptoms: Overdose would be expected to potentiate the known adverse effects of flibanserin, including severe hypotension, profound sedation, and syncope. CNS depression could progress to stupor or coma.

Management: There is no specific antidote for flibanserin overdose. Management consists of:

1. Supportive Care: This is the mainstay of treatment. Continuous cardiac and blood pressure monitoring is essential.
2. Symptomatic Treatment: Intravenous fluids and vasopressors may be required to manage hypotension. The patient should be placed in a supine position with legs elevated.
3. Gastric Lavage: May be considered if ingestion was very recent.
4. Activated Charcoal: Can be administered if the patient presents soon after ingestion.
5. Monitoring: Observe for a minimum of 24-48 hours due to the drug’s 11-hour half-life.

Storage

• Store at room temperature between 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°F).
• Keep in the original bottle or container to protect from light and moisture.
• Keep tightly closed.
• Keep out of reach of children and pets.

Disclaimer

This information is intended for educational purposes for healthcare professionals and is not a substitute for professional medical advice, diagnosis, or treatment. The prescribing healthcare provider is responsible for determining the appropriateness of flibanserin for an individual patient, considering their complete medical history, contraindications, and potential drug interactions. The prescriber and patient must be enrolled in the FDA-mandated REMS program. Always consult the FDA-approved full Prescribing Information, including the Boxed Warning regarding the risk of hypotension and syncope with alcohol use, before initiating therapy.

Reviews

Clinical trials and post-marketing surveillance provide the following expert consensus:

“Flibanserin offers a validated, non-hormonal pharmacologic option for a specific and distressing condition. Its efficacy, while modest in absolute terms, is statistically significant and clinically meaningful for a subset of premenopausal women with HSDD who have not found relief through counseling alone. The major limitation to its use is its significant safety profile, necessitating strict patient selection, comprehensive education on alcohol contraindication, and bedtime dosing. It is not a ‘female Viagra’ but rather a chronic-use modulator of central neurotransmitters. For the right patient—a healthy, premenopausal woman with true HSDD who can strictly adhere to the safety protocols—it can be a valuable tool in a multifaceted treatment approach.”