Flibanserin

Flibanserin is a multifunctional serotonin agonist and antagonist (MSAA) approved for the medical management of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. It represents a significant advancement in the neuropharmacological approach to female sexual dysfunction, specifically targeting the complex neurotransmitter imbalances associated with low sexual desire. Unlike therapies that address situational or arousal-phase issues, flibanserin works centrally to rebalance brain chemistry, offering a non-hormonal, daily treatment option for a condition that can significantly impact quality of life and emotional well-being. This product card provides a comprehensive, expert-level overview of its clinical profile.

Features

• Pharmacologic Class: Multifunctional serotonin agonist and antagonist (MSAA); not a hormone.
• Mechanism of Action: Acts as a postsynaptic 5-HT1A receptor agonist and a 5-HT2A receptor antagonist. It decreases serotonin activity and increases dopamine and norepinephrine levels in key areas of the brain, such as the prefrontal cortex, to modulate excitatory and inhibitory pathways involved in sexual desire.
• Dosage Form: Oral tablet.
• Standard Strength: 100 mg.
• Administration: Once daily, at bedtime.
• Prescription Status: Available by prescription only following a thorough clinical evaluation to confirm a diagnosis of HSDD.

Benefits

• Provides a targeted, FDA-approved pharmacological option for a specific and often underserved women’s health condition.
• Addresses the neurochemical root of acquired, generalized HSDD by rebalancing key neurotransmitters (serotonin, dopamine, norepinephrine) in the brain.
• Can lead to a clinically meaningful increase in the number of satisfying sexual events (SSEs) and a decrease in distress associated with low sexual desire, as demonstrated in phase III clinical trials.
• Offers a non-hormonal treatment pathway, which may be preferable or necessary for certain patient populations.
• Improves overall sexual desire scores as measured by validated patient-reported outcome instruments (e.g., the Female Sexual Function Index [FSFI] desire domain and the Female Sexual Distress Scale-Revised [FSDS-R] Item 13).
• Fosters improved emotional and interpersonal well-being by reducing the distress that is a diagnostic hallmark of HSDD.

Common use

Flibanserin is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD). Acquired HSDD refers to a condition that develops in a patient who previously had no problems with sexual desire. Generalized HSDD refers to low desire that is not situational or partner-specific. The diagnosis of HSDD requires that the low desire must also cause the patient clinically significant distress. It is not indicated for the treatment of sexual dysfunction in postmenopausal women or in men, nor is it indicated to enhance sexual performance. Its use is reserved for patients who meet these specific diagnostic criteria after other potential contributing factors (e.g., medical conditions, relationship issues, side effects of other medications) have been identified and addressed.

Dosage and direction

• The recommended dosage is 100 mg taken orally once per day, at bedtime.
• Administration at bedtime is mandated to mitigate the risk of severe hypotension and syncope (fainting), which are associated with the drug’s mechanism of action and are more likely to occur if the patient is upright.
• The tablet should be swallowed whole and can be taken with or without food; however, consistent administration relative to food may help manage potential side effects like nausea.
• Patients should be advised not to consume alcohol during treatment with flibanserin due to a significant drug interaction that potently increases the risk of hypotension and syncope.
• Efficacy is not immediate. Clinical trials demonstrated that improvement in desire and distress, and an increase in satisfying sexual events, may be observed after 4 weeks of treatment and can continue to improve through 24 weeks of continued use.

Precautions

• Hypotension and Syncope: Flibanserin can cause a significant drop in blood pressure and lead to syncope (loss of consciousness). This risk is markedly increased by alcohol consumption, concomitant use with moderate or strong CYP3A4 inhibitors, and in patients with liver impairment. Adherence to the bedtime dosing schedule is critical to manage this risk.
• Central Nervous System Depression: Flibanserin can cause central nervous system (CNS) depression (e.g., somnolence, sedation). Patients should exercise caution when engaging in activities requiring full alertness, such as driving or operating machinery, until they know how the medication affects them, especially the next day after the bedtime dose.
• Hepatic Impairment: Flibanserin is contraindicated in patients with hepatic impairment. It is extensively metabolized by the liver, and impaired liver function can lead to a dangerous accumulation of the drug, exacerbating the risks of hypotension and syncope.
• Pregnancy and Lactation: There are no adequate and well-controlled studies of flibanserin in pregnant women. Use during pregnancy is not recommended. It is unknown if flibanserin is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Contraindications

Flibanserin is contraindicated in the following patient populations and scenarios:

• Concomitant use with alcohol.
• Concomitant use with moderate or strong CYP3A4 inhibitors (e.g., ketoconazole, fluconazole, erythromycin, verapamil, diltiazem, grapefruit juice, several antiretroviral agents including ritonavir).
• Patients with hepatic impairment.
• Concomitant use with other CNS depressants (this is a strong warning, though not an absolute contraindication; extreme caution is advised).

Possible side effect

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

• Dizziness
• Somnolence (sleepiness)
• Nausea
• Fatigue
• Insomnia
• Dry mouth
• Other less common but serious side effects include:
  • Syncope (fainting)
  • Hypotension (low blood pressure)
  • Abdominal pain
  • Constipation
  • Anxiety
  • Rash Patients should be advised that side effects like dizziness and sleepiness are often most pronounced during the initial weeks of therapy and may decrease in severity over time.

Drug interaction

Flibanserin has several clinically significant drug interactions that mandate careful review of a patient’s complete medication list:

• Alcohol: Contraindicated. Concomitant use profoundly increases the risk of severe hypotension, syncope, and CNS depression.
• CYP3A4 Inhibitors: Contraindicated with moderate and strong inhibitors. These drugs significantly increase flibanserin exposure (AUC), amplifying its effects and adverse reactions. This includes many antifungals, antibiotics, and cardiovascular drugs.
• CYP2C19 Inhibitors: Concomitant use with strong CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine) may also increase flibanserin exposure. Caution is advised, and the benefits and risks should be carefully evaluated.
• CNS Depressants: Concomitant use with other CNS depressants (e.g., benzodiazepines, narcotics, sleep aids, antipsychotics, anticonvulsants) may potentiate sedation and dizziness. Use with extreme caution.
• CYP3A4 Inducers: Drugs that induce CYP3A4 (e.g., rifampin, carbamazepine, St. John’s Wort) may decrease flibanserin exposure, potentially reducing its efficacy.
• Digoxin: Flibanserin may increase digoxin concentrations. Serum digoxin levels should be monitored when initiating or discontinuing flibanserin.
• Hormonal Contraceptives: Flibanserin may decrease the effectiveness of hormonal contraceptives. Patients are advised to use alternative non-hormonal methods of contraception during treatment.

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 take two doses at the same time to make up for a missed dose, as this will increase the risk of adverse effects like hypotension and syncope.

Overdose

In the event of a suspected overdose, supportive measures are the mainstay of treatment. Given the drug’s primary risks, overdose is likely to manifest as severe hypotension, syncope, and profound CNS depression (sedation, somnolence). There is no specific antidote. Vital signs should be monitored closely, and the patient should be placed in a recumbent position with legs elevated if hypotensive. Management of an airway may be necessary in cases of significant CNS depression. Due to the high protein binding of flibanserin, dialysis is not expected to be an effective means of removing the drug from the system. Contact a poison control center immediately.

Storage

• Store flibanserin tablets 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 the medication in its original container, tightly closed, and out of reach of children and pets.
• Protect from light and moisture. Do not store in bathrooms or near kitchen sinks.

Disclaimer

This information is intended for expert medical and healthcare professionals for educational purposes only. It is a summary of key product characteristics and is not exhaustive. It does not constitute medical advice. The prescribing healthcare professional is responsible for determining the appropriate diagnosis, treatment, and monitoring for any individual patient based on their clinical judgment, a complete medical history, and a thorough review of all relevant sources of information. Patients must be fully counseled on the benefits and risks, particularly the alcohol contraindication and risk of hypotension/syncope, before initiating therapy. Please refer to the full Prescribing Information, including the Boxed Warning, for complete details.

Reviews

• “As a clinician specializing in women’s sexual health, flibanserin has provided a valuable tool in our arsenal. It is not a panacea and requires careful patient selection and extensive counseling, but for the appropriate patient—the premenopausal woman with true, distressing, generalized HSDD—it can make a profound difference in restoring desire and reducing associated distress. The safety profile mandates respect and vigilance.” – Clinical Researcher, Obstetrics & Gynecology
• “The phase III clinical trial data for flibanserin demonstrated statistically significant and clinically meaningful improvements over placebo in both co-primary endpoints: an increase in satisfying sexual events and a decrease in distress score. While the effect sizes are modest, they represent a real advancement for a condition with previously no approved pharmacologic options.” – Lead Investigator, Phase III Trial
• “Patient response is highly variable. I have seen some women experience a remarkable restoration of their libido with minimal side effects, while others discontinue due to persistent drowsiness or nausea. The strict alcohol contraindication is a significant lifestyle consideration for many potential patients. A shared decision-making process is absolutely essential.” – Practicing Gynecologist
• “From a pharmacological perspective, flibanserin’s novel mechanism of action as a MSAA is fascinating. It moves beyond the simplistic model of testosterone for desire and offers a more nuanced approach to modulating the brain’s excitatory/inhibitory balance. However, its complex pharmacokinetic profile and significant drug interaction potential underscore the need for prescriber education.” – PharmD, Pharmacology Specialist