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Less frequently reported adverse effects in clinical trials include anxiety, constipation, abdominal pain, sedation, accidental injury, appendicitis, and vertigo.

• Direct comparison trials between flibanserin and bremelanotide are lacking.
• Choice of treatment depends on patient preference, risk profile, and cost.
• Psychological and interpersonal factors are important contributors to HSDD.
• Combining medication with sex therapy or counseling may improve outcomes.
• Flibanserin does not increase libido in individuals without HSDD.
• It is not approved or intended for use as a recreational or enhancement drug.
• Off-label use, such as in postmenopausal women or men, is not supported by evidence.
• Healthcare providers must complete an online knowledge assessment for REMS certification.
• Certification must be renewed periodically according to the REMS program.

CNS depressants: CNS depressants, such as diphenhydramine, opioids, hypnotics, and benzodiazepines, pose an elevated risk of CNS depression when used concurrently with flibanserin compared to the use of flibanserin alone.

Further information

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 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.

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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 tadapox tablets 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.

Black Box Warnings

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. Healthcare professionals should engage in a comprehensive discussion with the patient regarding the concomitant use of other CNS depressants when prescribing flibanserin, considering the potential risks and benefits. The coadministration of flibanserin with alcohol is addressed explicitly in box warnings.

Strong or moderate CYP3A4 inhibitors: Strong or moderate CYP3A4 inhibitors, including azole antifungals and protease inhibitors, warrant careful consideration in assessing a patient's current medication regimen.

Healthcare professionals should know and inquire about these potential interactions to ensure safe prescribing practices.

INDICATION AND IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING

Due to the potential for adverse reactions, including sedation in a breastfed infant, breastfeeding is not recommended during flibanserin treatment. Pediatric patients: Flibanserin is not approved by the FDA for use in the pediatric population. Older patients: Flibanserin lacks FDA approval for use in older individuals, as its safety and efficacy in this age group have not been confirmed. The most frequently reported adverse effects of flibanserin, with an incidence of over 2%, include dizziness, somnolence, nausea, fatigue, insomnia, and dry mouth, listed in descending order of frequency. [15][14] Hypotension and syncope may manifest if flibanserin is combined with moderate or potent CYP3A4 inhibitors in individuals with hepatic impairment, alcohol, or other medications known for inducing hypotension and syncope. [15] Moderate or strong CYP3A4 inhibitors increase the plasma levels of flibanserin, thereby increasing the risk of syncope and hypotension.

Side effects

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.

Keys to patient success

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.

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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, sex tablet 100mg 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. Consequently, the combination of these medications with flibanserin is contraindicated.

• Flibanserin was developed by Boehringer Ingelheim, later licensed to Sprout Pharmaceuticals.
• It is considered a "female Viagra," though its mechanism differs from male erectile drugs.
• The medication is part of the growing field of female sexual dysfunction treatment.
• Most clinical trials showed a modest increase in satisfying sexual events.
• Flibanserin should be taken consistently for best results.
• It is not recommended for women who are pregnant or breastfeeding.
• Common adverse reactions include dry mouth and insomnia.
• The drug was approved after extensive clinical trials involving thousands of women.
• Long-term safety data is still being collected.

When a patient is taking a moderate or strong CYP3A4 inhibitor and plans to start taking flibanserin, it is essential to wait for at least 2 weeks after the last dose of the inhibitor to help minimize the risk of potential drug interactions and having elevated levels of flibanserin in the body.

• In 2019, the FDA required updates to the prescribing information regarding liver injury.
• Cases of hepatitis and liver enzyme elevations were reported post-marketing.
• Patients should be monitored for symptoms of liver injury (jaundice, dark urine).
• Discontinue flibanserin if liver injury is suspected.
• The REMS was modified to strengthen the warning about hepatotoxicity.
• Patients with signs of liver disease should not start flibanserin.
• Baseline liver enzyme testing is now considered a standard part of patient assessment.
• Follow-up testing may be recommended based on clinical judgment.
• The overall incidence of serious liver injury appears to be low.

Clinicians or prescribers should commence the moderate or strong CYP3A4 inhibitor 2 days after the last dose of flibanserin.

This allows sufficient time for the drug's clearance from the system, ensuring safe and effective treatment while minimizing the risk of potential drug interactions and adverse effects. CYP3A4 inducers: CYP3A4 inducers, including carbamazepine, phenobarbital, phenytoin, rifampin, rifabutin, rifapentine, and St John's Wort, significantly reduce flibanserin exposure when used concurrently.

Addyi is the #1 Prescribed Treatment by doctors for HSDD.1

[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.

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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.

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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.