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Flibanserin response

MedGen UID:
1170598
•Concept ID:
CN507895
•
Sign or Symptom
Synonym: ADDYI response
Drug:
Flibanserin
MedGen UID:
156695
•Concept ID:
C0754280
•
Pharmacologic Substance
An orally bioavailable, non-hormonal, multifunctional serotonin agonist and antagonist (MSAA) that may improve sexual desire and arousal in women. Upon oral administration, flibanserin selectively binds to serotonin receptors in the central nervous system, acting as an agonist on 5-HT1A receptors and an antagonist on 5-HT2A receptors. Agonist activity at 5-HT1A postsynaptic receptors may enhance the release of dopamine and other monoamines. Combined with 5-HT2A antagonism, flibanserin boosts levels of dopamine in the mesocortical area of the prefrontal cortex and produces a net increase of norepinephrine selectively in the prefrontal cortex through disinhibition of locus coeruleus noradrenergic neurons. In addition, flibanserin reduces concentrations of serotonin in the prefrontal cortex with chronic administration. Reducing serotonin, which modulates sexual activity in an inhibitory fashion through downstream decreases in dopamine release, while enhancing the release of norepinephrine and dopamine in the prefrontal cortex may improve sexual desire and interest. [from NCI]
Flibanserin
 
Gene (location): CYP2C19 (10q23.33)

Definition

Flibanserin is indicated for the treatment of “hypoactive sexual desire disorder” (HSDD) in premenopausal women. It is the first drug to be approved by the FDA for female sexual dysfunction. Flibanserin acts on central serotonin receptors and was initially developed to be an antidepressant. Although it was not effective for depression, flibanserin did appear to increase sex drive. The use of flibanserin is limited by modest efficacy and the risk of severe hypotension and syncope (fainting). This risk is increased by alcohol, and by medications that inhibit CYP3A4 (the primary enzyme that metabolizes flibanserin). Consequently, alcohol use is contraindicated during flibanserin therapy, and flibanserin is contraindicated in individuals taking moderate or strong CYP3A4 inhibitors, which include several antibiotics, antiviral agents, cardiac drugs, and grapefruit juice. The CYP2C19 enzyme also contributes to the metabolism of flibanserin, and individuals who lack CYP2C19 activity (“CYP2C19 poor metabolizers”) have a higher exposure to flibanserin than normal metabolizers. The risk of hypotension, syncope, and CNS depression may be increased in individuals who are CYP2C19 poor metabolizers, according to the FDA-approved drug label, which also states that approximately 2–5% of Caucasians and Africans and 2–15% of Asians are CYP2C19 poor metabolizers. However, the drug label does not provide alternative dosing for poor metabolizers. The standard recommended dosage of flibanserin is 100 mg once per day, taken at bedtime. [from Medical Genetics Summaries]

Additional description

From NCBI curation
Flibanserin is indicated for the treatment of “hypoactive sexual desire disorder” (HSDD) in premenopausal women. It is the first drug to be approved by the FDA for female sexual dysfunction. Flibanserin acts on central serotonin receptors and was initially developed to be an antidepressant. Although it was not effective for depression, flibanserin did appear to increase sex drive. The use of flibanserin is limited by modest efficacy and the risk of severe hypotension and syncope (fainting). This risk is increased by alcohol, and by medications that inhibit CYP3A4 (the primary enzyme that metabolizes flibanserin). Consequently, alcohol use is contraindicated during flibanserin therapy, and flibanserin is contraindicated in individuals taking moderate or strong CYP3A4 inhibitors, which include several antibiotics, antiviral agents, cardiac drugs, and grapefruit juice. The CYP2C19 enzyme also contributes to the metabolism of flibanserin, and individuals who lack CYP2C19 activity (“CYP2C19 poor metabolizers”) have a higher exposure to flibanserin than normal metabolizers. The risk of hypotension, syncope, and CNS depression may be increased in individuals who are CYP2C19 poor metabolizers, according to the FDA-approved drug label, which also states that approximately 2–5% of Caucasians and Africans and 2–15% of Asians are CYP2C19 poor metabolizers. However, the drug label does not provide alternative dosing for poor metabolizers. The standard recommended dosage of flibanserin is 100 mg once per day, taken at bedtime.

Professional guidelines

PubMed

Repurposing Drugs for Treatment of Age-Related Macular Degeneration.
Francisco SG, Rowan S
Adv Exp Med Biol 2023;1415:73-77. doi: 10.1007/978-3-031-27681-1_12. PMID: 37440017
Medical Treatment of Female Sexual Dysfunction.
Nappi RE, Tiranini L, Martini E, Bosoni D, Righi A, Cucinella L
Urol Clin North Am 2022 May;49(2):299-307. doi: 10.1016/j.ucl.2022.02.001. PMID: 35428435
Hypoactive Sexual Desire Disorder in Women: Physiology, Assessment, Diagnosis, and Treatment.
Pettigrew JA, Novick AM
J Midwifery Womens Health 2021 Nov;66(6):740-748. Epub 2021 Sep 12 doi: 10.1111/jmwh.13283. PMID: 34510696Free PMC Article

Curated

DailyMed Drug Label, ADDYI- flibanserin tablet, film coated, 2021

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted 1 information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2015 Statement from the US Food and Drug Administration (FDA): CYP2C19 poor metabolizers had increased flibanserin exposures compared to CYP2C19 extensive metabolizers. Additionally, syncope occurred in a subject who was a CYP2C19 poor metabolizer. Therefore, increase monitoring for adverse reactions (e.g., hypotension) in patients who are CYP2C19 poor metabolizers. The frequencies of poor CYP2C19 metabolizers are approximately 2–5% among Caucasians and Africans and approximately 2– 15% among Asians.

Please review the complete therapeutic recommendations that are located here: (1).

1 The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug. Certain terms, genes and genetic variants may be corrected in accordance to nomenclature standards, where necessary. We have given the full name of abbreviations, shown in square brackets, where necessary.

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