FDA approves expanded use of flibanserin for hypoactive sexual desire disorder in women

HSDD is characterized by limited or absent sexual fantasies or desires, resulting in interpersonal strain or heightened distress, which persist for a minimum of 6 months. Flibanserin is specifically indicated for patients whose diagnosis is unrelated to relationship issues, psychiatric or medical conditions, or the effects of medication or drugs. Recent trials involving premenopausal women who have endured HSDD for a minimum of 6 months have further reinforced the drug's potential as a practical therapeutic option.

This makes flibanserin a pivotal choice for premenopausal women experiencing primary HSDD. This activity covers flibanserin's indications, contraindications, mechanism of action, administration, monitoring, and toxicity. This activity aims to enhance collaboration among healthcare professionals for improved management of HSDD in patients using flibanserin, ultimately leading to more effective patient care and superior outcomes. Identify the specific indications for flibanserin use in premenopausal women with hypoactive sexual desire disorder, distinguishing it from other therapeutic options. Assess patients for potential contraindications and monitor for adverse effects, ensuring ongoing assessment of the medication's impact on sexual function and overall well-being.

Microcircuits and Sexual Interest and Desire

Flibanserin selectively targets central serotonin postsynaptic receptors, exhibiting both agonistic and antagonistic effects on 5-HT1A and 5-HT2A, respectively. Flibanserin's activity on these specific serotonin receptors distinguishes it from other drugs targeting serotonin receptors. The activity of flibanserin on 5-HT1A and 5-HT2A receptors leads to elevated NE and DA levels and reduced serotonin levels within the prefrontal cortex intracellularly. Alongside its targeted effects on postsynaptic serotonin receptors, flibanserin exhibits limited antagonistic activity on 5-HT2B, 5-HT2C, and DA D4 receptors. [3][11] Flibanserin is not associated with addiction or misuse potential, as it does not alter dopaminergic neurotransmission in the nucleus accumbens.

Serious Adverse Effects

Absorption: In healthy premenopausal women, the oral administration of a 100 mg dose of flibanserin results in a time to reach a maximum plasma concentration of approximately 0.75 hours. The absolute bioavailability of flibanserin after oral dosing is 33%. Distribution: Flibanserin binds primarily to albumin, exhibiting a plasma protein binding of approximately 98%. Metabolism: Flibanserin undergoes primary metabolism through the cytochrome P450 enzymes lady era tablets CYP3A4 and CYP2C19,[12] with minimal contributions to its metabolism made from CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2D6 based on in vitro and in vivo data. Flibanserin undergoes extensive metabolism, resulting in at least 35 metabolites, most of which are present in low concentrations in plasma. Apply knowledge of flibanserin's mechanism of action into clinical decision-making, aligning its pharmacological effects with patient-specific factors. Collaborate with other healthcare professionals to enhance interdisciplinary approaches in managing hypoactive sexual desire disorder, fostering comprehensive and patient-centered care. Sexual dysfunction affects approximately 50% of women in the United States. Among the various factors contributing to sexual dysfunction in women, hypoactive sexual desire disorder (HSDD) is the most commonly identified cause. [1][2] The diagnosis of this condition is unrelated to relationship issues, psychiatric or medical conditions, or the effects of medication or drugs.

Although the exact physiological causes of HSDD remain inconclusive, a hypothesis suggests that HSDD may be influenced by neurotransmitter function and hormonal levels. Flibanserin is the first medication approved by the U.S.

Side effects

Among these, only 2 metabolites—6,21-dihydroxy-flibanserin-6,21-disulfate and 6-hydroxy-flibanserin-6-sulfate—exhibit plasma concentrations comparable to flibanserin. Notably, both of these metabolites are inactive. The average terminal half-life of flibanserin is approximately 11 hours. Flibanserin is available in a 100 mg oral tablet form and is administered once daily at bedtime. Flibanserin is recommended to be taken at bedtime to minimize the risk of hypotension, syncope, accidental injury, or central nervous system (CNS) depression during waking hours.

Approval process and advocacy

In case of a missed dose, patients are recommended to take it the following night without doubling the dosage. If the patient does not report any improvement in their symptoms after 8 weeks of compliance with the medication, flibanserin should be discontinued. Healthcare professionals should carefully consider concomitant medications outlined in the drug interactions. Healthcare providers should exercise caution when prescribing flibanserin in conjunction with potent CYP2C19 inhibitors. The combination of these medications has been associated with heightened adverse reactions, likely stemming from presumed elevated levels of flibanserin. Food and Drug Administration (FDA) in 2015 for the management of HSDD in premenopausal women. [3] The American College fildena purple pill of Obstetricians and Gynecologists (ACOG) supports the use of flibanserin for premenopausal women experiencing HSDD. [4] The American Psychiatric Association's guidelines also acknowledge flibanserin as a viable treatment option for HSDD. Although flibanserin was initially developed to treat depression, studies revealed its ineffectiveness as an antidepressant compared to a placebo. However, these initial studies did identify positive results in terms of sexual function. [6] Subsequently, the effectiveness of flibanserin was analyzed through several clinical trials—3 of which involved premenopausal women who had experienced HSDD for a minimum of 6 months. The participants in the study had a mean age of 36, a relationship duration of 11 years, and an HSDD duration of 5 years. Clinical trial results demonstrated statistical significance in endpoint measurements, utilizing the Female Sexual Function Index (FSFI) and satisfying sexual events (SSE). The FSFI addressed the following 2 questions: "Over the past 4 weeks, how often did you feel sexual desire or interest?" "Over the past 4 weeks, how would you rate your level of sexual desire or interest?" Furthermore, patient responses to the statement, "Indicate your most intense level of sexual desire." For both endpoint measurements, values were calculated on a scale of 1 to 5 (ranging from almost never or never to almost always or always) or 0 to 3 (ranging from no desire to strong desire). All 3 clinical trials included an additional endpoint assessing, "How often did you feel bothered by low sexual desire?" on a scale of 0 to 4 (ranging from never to always) over 7 days.

• Potential for negative publicity and stigma surrounding a "pink Viagra."
• Media coverage often oversimplifies its mechanism and expected results.
• Patient education is crucial to set realistic expectations about benefits.
• Support groups and online communities exist for women discussing HSDD treatment.
• Ongoing research continues to explore other pharmacologic targets for HSDD.
• Future developments may include new formulations or combination therapies.
• The approval of flibanserin spurred increased investment in female sexual health.
• It remains a subject of debate in medical ethics, women's health, and drug regulation.
• Prescribers should stay updated on post-marketing safety communications.

The results of this endpoint were comparable to that of the FSFI score, suggesting improvement in sexual satisfaction. The mean change from baseline at week 24 was approximately 0.7 for FSFI and -0.7 for the additional endpoint. [9][10] Serotonin influences various physiological functions, including sexual desire. The negative regulation of libido occurs through microcircuits at sites where serotonin and prolactin exert their actions. This suggests that an imbalance in these microcircuits may contribute to the development of HSDD, indicating reduced levels of DA and NE and increased amounts of 5-HT.

Flibanserin selectively targets central serotonin postsynaptic receptors, exhibiting both agonistic and antagonistic effects on 5-HT1A and 5-HT2A, respectively.

Bottom Line

Sexual dysfunction affects approximately 50% of women in the United States. Among the various factors contributing to sexual dysfunction in women, hypoactive sexual desire disorder (HSDD) is the most commonly identified cause. [1][2] The diagnosis of this condition is unrelated to relationship issues, psychiatric or medical conditions, or the effects of medication or drugs. Although the exact physiological causes of HSDD remain inconclusive, a hypothesis suggests that HSDD may be influenced by neurotransmitter function and hormonal levels. Flibanserin is the first medication approved by the U.S.

Key Takeaways

Food and Drug Administration (FDA) in 2015 for the management of HSDD in premenopausal women. [3] The American College fildena purple pill of Obstetricians and Gynecologists (ACOG) supports the use of flibanserin for premenopausal women experiencing HSDD. [4] The American Psychiatric Association's guidelines also acknowledge flibanserin as a viable treatment option for HSDD. Although flibanserin was initially developed to treat depression, studies revealed its ineffectiveness as an antidepressant compared to a placebo. However, these initial studies did identify positive results in terms of sexual function. Flibanserin's activity on these specific serotonin receptors distinguishes it from other drugs targeting serotonin receptors. The activity of flibanserin on 5-HT1A and 5-HT2A receptors leads to elevated NE and DA levels and reduced serotonin levels within the prefrontal cortex intracellularly. Alongside its targeted effects on postsynaptic serotonin receptors, flibanserin exhibits limited antagonistic activity on 5-HT2B, 5-HT2C, and DA D4 receptors.

Further reading

Upon its approval in August 2015, flibanserin required a Risk Evaluation and Mitigation Strategy (REMS) program that included Elements to Assure Safe Use (ETASU), which mandated certification for both prescribers and pharmacists. [14] However, in 2019, the FDA replaced the original REMS with a medication-guide-only REMS, eliminating the certification requirement for prescribers or pharmacists. Pharmacogenetics: Clinicians should be mindful of pharmacogenetic variations to mitigate the risk of adverse effects related to flibanserin, particularly in patients identified as poor CYP2C19 metabolizers. Individuals classified as poor CYP2C19 metabolizers may experience elevated levels of flibanserin, heightening the risk of adverse events such as hypotension, syncope, and CNS depression. This subgroup constitutes 2% to 5% of Caucasians and Africans and 2% to 15% of Asians.

Missed Dose Instructions

Hepatic impairment: Mild hepatic impairment (Child-Pugh score of 5 to 6 points) showed that single 50 mg oral doses of flibanserin led to increased systemic exposure and a longer half-life than those with normal hepatic function. Due to the limited sample size in moderate hepatic impairment (Child-Pugh score of 8 to 9 points), conclusive statements regarding the impact of flibanserin exposure cannot be asserted. Notably, flibanserin is contraindicated for hepatic impairment. Renal impairment: The pharmacokinetic data in the labeling indicates a slight increase in the area under the curve (AUC) by 1.1-fold in mild-to-moderate renal impairment and a 1.2-fold increase in AUC for severe renal impairment compared to healthy individuals. In addition, the data suggest that patients with renal impairment may not require dosage adjustments, as the observed alteration in AUC is minimal. [3][11] Flibanserin is not associated with addiction or misuse potential, as it does not alter dopaminergic neurotransmission in the nucleus accumbens.

Real Science. Real Results.

[6] Subsequently, the effectiveness of flibanserin was analyzed through several clinical trials—3 of which involved premenopausal women who had experienced HSDD for a minimum of 6 months. The participants in the study had a mean age of 36, a relationship duration of 11 years, and an HSDD duration of 5 years. Clinical trial results demonstrated statistical significance in endpoint measurements, utilizing the Female Sexual Function Index (FSFI) and satisfying sexual events (SSE). The FSFI addressed the following 2 questions: "Over the past 4 weeks, how often did you feel sexual desire or interest?" "Over the past 4 weeks, how would you rate your level of sexual desire or interest?" Furthermore, patient responses to the statement, "Indicate your most intense level of sexual desire." For both endpoint measurements, values were calculated on a scale of 1 to 5 (ranging from almost never or never to almost always or always) or 0 to 3 (ranging from no desire to strong desire). All 3 clinical trials included an additional endpoint assessing, "How often did you feel bothered by low sexual desire?" on a scale of 0 to 4 (ranging from never to always) over 7 days.

Common Adverse Effects

The results of this endpoint were comparable to that of the FSFI score, suggesting improvement in sexual satisfaction. The mean change from baseline at week 24 was approximately 0.7 for FSFI and -0.7 for the additional endpoint. [9][10] Serotonin influences various physiological functions, including sexual desire. The negative regulation of libido occurs through microcircuits at sites where serotonin and prolactin exert their actions. This suggests that an imbalance in these microcircuits may contribute to the development of HSDD, indicating reduced levels of DA and NE and increased amounts of 5-HT. Absorption: In healthy premenopausal women, the oral administration of a 100 mg dose of flibanserin results in a time to reach a maximum plasma concentration of approximately 0.75 hours. The absolute bioavailability of flibanserin after oral dosing is 33%. Distribution: Flibanserin binds primarily to albumin, exhibiting a plasma protein binding of approximately 98%.

Peds Dosing .

HSDD is characterized by limited or absent sexual fantasies or desires, resulting in interpersonal strain or heightened distress, which persist for a minimum of 6 months. Flibanserin is specifically indicated for patients whose diagnosis is unrelated to relationship issues, psychiatric or medical conditions, or the effects of medication or drugs. Recent trials involving premenopausal women who have endured HSDD for a minimum of 6 months have further reinforced the drug's potential as a practical therapeutic option. This makes flibanserin a pivotal choice for premenopausal women experiencing primary HSDD. This activity covers flibanserin's indications, contraindications, mechanism of action, administration, monitoring, and toxicity.

A note about sex and gender

This activity aims to enhance collaboration among healthcare professionals for improved management of HSDD in patients using flibanserin, ultimately leading to more effective patient care and superior outcomes. Identify the specific indications for flibanserin use in premenopausal women with hypoactive sexual desire disorder, distinguishing it from other therapeutic options. Assess patients for potential contraindications and monitor for adverse effects, ensuring ongoing assessment of the medication's impact on sexual function and overall well-being. Apply knowledge of flibanserin's mechanism of action into clinical decision-making, aligning its pharmacological effects with patient-specific factors. Collaborate with other healthcare professionals to enhance interdisciplinary approaches in managing hypoactive sexual desire disorder, fostering comprehensive and patient-centered care. Metabolism: Flibanserin undergoes primary metabolism through the cytochrome P450 enzymes lady era tablets CYP3A4 and CYP2C19,[12] with minimal contributions to its metabolism made from CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2D6 based on in vitro and in vivo data. Flibanserin undergoes extensive metabolism, resulting in at least 35 metabolites, most of which are present in low concentrations in plasma. Among these, only 2 metabolites—6,21-dihydroxy-flibanserin-6,21-disulfate and 6-hydroxy-flibanserin-6-sulfate—exhibit plasma concentrations comparable to flibanserin. Notably, both of these metabolites are inactive.

• Flibanserin's mechanism involves increasing dopamine and norepinephrine and decreasing serotonin levels.
• It does not address libido caused by relationship issues or physical health problems.
• Flibanserin was once controversial due to debates over its effectiveness.
• It is not suitable for women taking certain antidepressants due to drug interactions.
• The medication has warnings for severe hypotension and syncope.
• Patients are advised to avoid alcohol consumption completely while on the drug.
• Flibanserin's approval was considered a breakthrough for female sexual health.
• Insurance coverage for flibanserin varies and can be limited.
• The drug's marketing emphasizes the importance of patient counseling.

The average terminal half-life of flibanserin is approximately 11 hours. Flibanserin is available in a 100 mg oral tablet form and is administered once daily at bedtime. Flibanserin is recommended to be taken at bedtime to minimize the risk of hypotension, syncope, accidental injury, or central nervous system (CNS) depression during waking hours. In case of a missed dose, patients are recommended to take it the following night without doubling the dosage.

• Reporting of adverse events is encouraged through the FDA MedWatch program.
• Healthcare providers should report syncope, severe hypotension, or liver injury.
• Post-marketing surveillance is critical for understanding rare, long-term risks.
• Drug utilization reviews track prescribing patterns and potential misuse.
• In case of suspected pregnancy, patients should contact their doctor immediately.
• Animal studies showed developmental toxicity at doses much higher than human dose.
• Lactation studies in animals showed excretion in milk; human data are lacking.
• Decision to breastfeed while on flibanserin requires weighing potential risks.
• The benefit for an individual patient must justify the potential risk to a fetus/infant.

If the patient does not report any improvement in their symptoms after 8 weeks of compliance with the medication, flibanserin should be discontinued. Healthcare professionals should carefully consider concomitant medications outlined in the drug interactions. Healthcare providers should exercise caution when prescribing flibanserin in conjunction with potent CYP2C19 inhibitors. The combination of these medications has been associated with heightened adverse reactions, likely stemming from presumed elevated levels of flibanserin. Upon its approval in August 2015, flibanserin required a Risk Evaluation and Mitigation Strategy (REMS) program that included Elements to Assure Safe Use (ETASU), which mandated certification for both prescribers and pharmacists. [14] However, in 2019, the FDA replaced the original REMS with a medication-guide-only REMS, eliminating the certification requirement for prescribers or pharmacists. Pharmacogenetics: Clinicians should be mindful of pharmacogenetic variations to mitigate the risk of adverse effects related to flibanserin, particularly in patients identified as poor CYP2C19 metabolizers. Individuals classified as poor CYP2C19 metabolizers may experience elevated levels of flibanserin, heightening the risk of adverse events such as hypotension, syncope, and CNS depression. This subgroup constitutes 2% to 5% of Caucasians and Africans and 2% to 15% of Asians. Hepatic impairment: Mild hepatic impairment (Child-Pugh score of 5 to 6 points) showed that single 50 mg oral doses of flibanserin led to increased systemic exposure and a longer half-life than those with normal hepatic function. Due to the limited sample size in moderate hepatic impairment (Child-Pugh score of 8 to 9 points), conclusive statements regarding the impact of flibanserin exposure cannot be asserted. Notably, flibanserin is contraindicated for hepatic impairment. Renal impairment: The pharmacokinetic data in the labeling indicates a slight increase in the area under the curve (AUC) by 1.1-fold in mild-to-moderate renal impairment and a 1.2-fold increase in AUC for severe renal impairment compared to healthy individuals. In addition, the data suggest that patients with renal impairment may not require dosage adjustments, as the observed alteration in AUC is minimal. The FDA-approved labeling does not specify any dosage adjustments for renal impairment. Pregnancy considerations: An ongoing flibanserin pregnancy registry study assesses pregnancy outcomes in women exposed to flibanserin at any stage of pregnancy ( To date, no studies on pregnant women have conclusively identified any drug-associated risks.

• The pharmacology of flibanserin demonstrates a complex serotonin-dopamine interplay.
• The medication is not a substitute for addressing relationship or psychological factors.
• It is essential to evaluate contraindications before prescribing flibanserin.
• The drug's societal impact includes increased awareness of female sexual health.
• Use during pregnancy is contraindicated due to unknown risks.
• Flibanserin requires healthcare provider supervision due to its safety profile.
• Its effectiveness varies, necessitating personalized treatment approaches.
• Ongoing studies seek to expand understanding of its benefits and risks.
• The medication represents a milestone in female sexual medicine advancements.

However, studies based on animals have indicated certain adverse effects on reproduction and development, including diminished fetal weight, structural anomalies, and increased fetal loss, observed at exposures significantly exceeding the maximum recommended human dosage. Notably, although flibanserin is not recommended during pregnancy, it is also not contraindicated in this population. Breastfeeding considerations: Although flibanserin has been detected in rat milk, its presence in human milk and its impact on the breastfed infant and milk production remains unknown.

More about flibanserin

The FDA-approved labeling does not specify any dosage adjustments for renal impairment. Pregnancy considerations: An ongoing flibanserin pregnancy registry study assesses pregnancy outcomes in women exposed to flibanserin at any stage of pregnancy ( To date, no studies on pregnant women have conclusively identified any drug-associated risks. However, studies based on animals have indicated certain adverse effects on reproduction and development, including diminished fetal weight, structural anomalies, and increased fetal loss, observed at exposures significantly exceeding the maximum recommended human dosage. Notably, although flibanserin is not recommended during pregnancy, it is also not contraindicated in this population. Breastfeeding considerations: Although flibanserin has been detected in rat milk, its presence in human milk and its impact on the breastfed infant and milk production remains unknown.

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