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			{{Short description|Medication}}
	{{drugbox
			{{Use dmy dates|date=August 2024}}
			{{cs1 config |name-list-style=vanc |display-authors=6}}
			{{Infobox drug
	| Verifiedfields = changed		| Verifiedfields = changed
	| UNII_Ref = {{fdacite|changed|FDA}}		| Watchedfields = changed
			| verifiedrevid = 437139289
			| image = Flibanserin.svg
			| image2 = Flibanserin ball-and-stick model.png
			<!--Clinical data-->
			| tradename = Addyi
			| Drugs.com = {{drugs.com|monograph|flibanserin}}
			| DailyMedID = Flibanserin
			| routes_of_administration = ]
			| ATC_prefix = G02
			| ATC_suffix = CX02
			| legal_CA = Rx-only
			| legal_CA_comment = <ref>{{cite web | url=https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00348 | title=Regulatory Decision Summary for Addyi | date=23 October 2014 }}</ref>
			| legal_US = Rx-only
			| legal_US_comment = <ref name="Addyi FDA label" />
			<!--Pharmacokinetic data-->
			| bioavailability = 33%<ref name="Addyi FDA label">{{cite web | title=Addyi- flibanserin tablet, film coated | website=DailyMed | date=10 October 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394 | access-date=20 October 2020}}</ref>
			| protein_bound = ~98%
			| metabolism = Extensive by ] (mainly by ] and ])
			| elimination_half-life = ~11 hours
			| excretion = ] (51%), ] (44%)
			<!--Identifiers-->
			| IUPHAR_ligand = 8182
			| CAS_number_Ref = {{cascite|correct|??}}
			| CAS_number = 167933-07-5
			| PubChem = 6918248
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| ChemSpiderID = 5293454
			| ChEBI_Ref = {{ebicite|changed|EBI}}
			| ChEBI = 90865
			| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 37JK4STR6Z		| UNII = 37JK4STR6Z
			| KEGG_Ref = {{keggcite|correct|kegg}}
	| verifiedrevid = 407490953
			| KEGG = D02577
	| IUPAC_name = 1-(2-{4-piperazin-1-yl}ethyl)-1,3-dihydro-2''H''-benzimidazol-2-one
	| image = Flibanserin-structural.svg
	| InChI = 1/C20H21F3N4O/c21-20(22,23)15-4-3-5-16(14-15)26-11-8-25(9-12-26)10-13-27-18-7-2-1-6-17(18)24-19(27)28/h1-7,14H,8-13H2,(H,24,28)
	| InChIKey = PPRRDFIXUUSXRA-UHFFFAOYAA
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 231068		| ChEMBL = 231068
			| DrugBank = DB04908
			<!--Chemical data-->
			| IUPAC_name = 1-(2-<nowiki/>{4-piperazin-1-yl}ethyl)-1,3-dihydro-2''H''-benzimidazol-2-one
			| C=20 | H=21 | F=3 | N=4 | O=1
			| smiles = FC(F)(F)c4cc(N3CCN(CCN2c1ccccc1NC2=O)CC3)ccc4
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C20H21F3N4O/c21-20(22,23)15-4-3-5-16(14-15)26-11-8-25(9-12-26)10-13-27-18-7-2-1-6-17(18)24-19(27)28/h1-7,14H,8-13H2,(H,24,28)		| StdInChI = 1S/C20H21F3N4O/c21-20(22,23)15-4-3-5-16(14-15)26-11-8-25(9-12-26)10-13-27-18-7-2-1-6-17(18)24-19(27)28/h1-7,14H,8-13H2,(H,24,28)
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = PPRRDFIXUUSXRA-UHFFFAOYSA-N		| StdInChIKey = PPRRDFIXUUSXRA-UHFFFAOYSA-N
	| CAS_number = 167933-07-5
	| ATC_prefix = none
	| ATC_suffix =
	| PubChem = 6918248
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 5293454
	| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D02577
	| C = 20 | H = 21 | F = 3 | N = 4 | O = 1
	| molecular_weight = 390.40 g/mol
	| smiles = FC(F)(F)c4cc(N3CCN(CCN2c1ccccc1NC2=O)CC3)ccc4
	| bioavailability =
	| metabolism =
	| elimination_half-life =
	| excretion =
	| pregnancy_category =
	| legal_status = Uncontrolled
	| routes_of_administration = ]
	}}		}}
			<!-- Definition and medical uses -->
			'''Flibanserin''', sold under the brand name '''Addyi''', is a medication approved for the treatment of ] women with ] (HSDD).<ref name=pmid12177684>{{cite journal | vauthors = Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S | title = Pharmacology of flibanserin | journal = CNS Drug Reviews | volume = 8 | issue = 2 | pages = 117–142 | year = 2002 | pmid = 12177684 | pmc = 6741686 | doi = 10.1111/j.1527-3458.2002.tb00219.x | doi-access = free }}</ref><ref>{{cite journal | vauthors = Jolly E, Clayton A, Thorp J, Lewis-D'Agostino D, Wunderlich G, Lesko L |title=Design of Phase III pivotal trials of flibanserin in female Hypoactive Sexual Desire Disorder (HSDD) |journal=Sexologies |volume=17 |issue=Suppl 1 |pages=S133–4 |date=April 2008 |doi=10.1016/S1158-1360(08)72886-X }}</ref> The medication improves sexual desire, increases the number of satisfying sexual events, and decreases the distress associated with low sexual desire.<ref name=":0">{{Cite web |date=1 September 2021 |title=ADDYI- flibanserin tablet, film coated |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394 |access-date=14 November 2022 |website=DailyMed}}</ref> The most common side effects are ], sleepiness, ], difficulty falling asleep or staying asleep and dry mouth.<ref name=":0" />
			] by ] was halted in October 2010, following a negative evaluation by the US ] (FDA).<ref name=spon>Spiegel online: , 8 October 2010 (in German)</ref> The rights to the drug were then transferred to Sprout Pharmaceuticals, which achieved approval of the drug by the US FDA in August 2015.<ref>{{cite journal | vauthors = Mullard A | title = FDA approves female sexual dysfunction drug | journal = Nature Reviews. Drug Discovery | volume = 14 | issue = 10 | pages = 669 | date = October 2015 | pmid = 26424353 | doi = 10.1038/nrd4757 | s2cid = 36380932 }}</ref>
	'''Flibanserin''' (code name '''BIMT-17'''; proposed trade name '''Girosa''') is a ] that was investigated by ] as a novel, non-hormonal treatment for pre-menopausal women with ] (HSDD).<ref>{{cite journal | doi = 10.1111/j.1527-3458.2002.tb00219.x | author = Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S|title = Pharmacology of flibanserin | journal = CNS Drug Rev.| volume = 8| issue = 2| pages = 117–142| year = 2002| month=summer | pmid = 12177684}}</ref><ref>{{cite journal |author=Jolly E, Clayton A, Thorp J, Lewis-D’Agostino D, Wunderlich G, Lesko L |title=Design of Phase III pivotal trials of flibanserin in female Hypoactive Sexual Desire Disorder (HSDD) |journal=Sexologies |volume=17 |issue=Suppl 1 |pages=S133–4 |month=April |year=2008 |doi=10.1016/S1158-1360(08)72886-X }}</ref> Development was terminated in October 2010 following a negative report by the ].<ref name=spon>Spiegel online: , 8 October 2010 (in German)</ref>
			Addyi is approved for medical use in the US for premenopausal women with HSDD and in Canada for premenopausal and postmenopausal women with HSDD.<ref name=":0" /><ref>{{Cite web |date=26 January 2021 |title=ADDYI Product Monograph |url=https://pdf.hres.ca/dpd_pm/00059744.PDF |access-date=14 November 2022 |website=Health Canada}}</ref>
	HSDD is the most commonly reported female sexual complaint and characterized by a decrease in sexual desire that causes marked personal distress and/or personal difficulties. According to prevalence studies about 1 in 10 women reported low sexual desire with associated distress, which may be HSDD.<ref>{{cite journal |author=Nygaard I |title=Sexual dysfunction prevalence rates: marketing or real? |journal=Obstet Gynecol |volume=112 |issue=5 |pages=968–9 |year=2008 |month=November |pmid=18978094 |doi=10.1097/01.AOG.0000335775.68187.b2 }}</ref> The neurobiological pathway of female sexual desire involves interactions among multiple neurotransmitters, sex hormones and various psychosocial factors. Sexual desire is modulated in distinct brain areas by a balance between inhibitory and excitatory neurotransmitters, serotonine acting as an inhibitor while dopamine and norepinephrine act as a stimulator of sexual desire.<ref>{{cite journal |author=Clayton AH |title=The pathophysiology of hypoactive sexual desire disorder in women |journal=Int J Gynaecol Obstet |volume=110 |issue=1 |pages=7–11 |month=July |year=2010 |pmid=20434725 |doi=10.1016/j.ijgo.2010.02.014 |url=http://www.ijgo.org/article/S0020-7292%2810%2900138-4/abstract}}</ref><ref name=Pfaus09>{{cite journal |author=Pfaus JG |title=Pathways of sexual desire |journal=J Sex Med |volume=6 |issue=6 |pages=1506–33 |year=2009 |month=June |pmid=19453889 |doi=10.1111/j.1743-6109.2009.01309.x}}</ref>
	Flibanserin is a 5-HT1A receptor agonist and 5-HT2A receptor antagonist that had initially been investigated as an ].<ref name="pmid9537806">{{cite journal |author=D'Aquila P, Monleon S, Borsini F, Brain P, Willner P |title=Anti-anhedonic actions of the novel serotonergic agent flibanserin, a potential rapidly-acting antidepressant |journal=European Journal of Pharmacology |volume=340 |issue=2-3 |pages=121–32 |year=1997 |month=December |pmid=9537806 |doi= 10.1016/S0014-2999(97)01412-X|url=}}</ref><ref>{{cite journal|author = Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R | url=http://www.nature.com/bjp/journal/v139/n7/full/0705341a.html | title= Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. | journal= Br J Pharmacol.| volume=139| issue=7| pages= 1281–8| year= 2003 | month= August | doi= 10.1038/sj.bjp.0705341|pmid = 12890707|pmc = 1573953}}</ref> Preclinical evidence suggested that flibanserin targets these receptors preferentially in selective brain areas and helps to restore a balance between these inhibitory and excitatory effects.<ref name=Pfaus09/><ref name=Allers10>{{cite journal |author=Allers K, Dremencov E, Ceci A, ''et al.'' |title=Acute and repeated flibanserin administration in female rats modulates monoamines differentially across brain areas: a microdialysis study |journal=J Sex Med |volume=7 |issue=5 |pages=1757–67 |month=May |pmid=20163532 |year=2010 |doi=10.1111/j.1743-6109.2010.01763.x }}</ref>
	HSDD has been recognized as a distinct sexual function disorder for more than 30 years.<ref>American Psychiatric Association. Sexual and gender identity disorders. In: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000:493–538.</ref>
			HSDD was recognized as a distinct sexual function disorder for more than 30 years, but was removed from the '']'' in 2013, and replaced with a new diagnosis called ] (FSIAD).<ref>American Psychiatric Association. Sexual and gender identity disorders. In: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000:493–538.</ref><ref>{{cite news|url=https://www.nytimes.com/2015/02/27/opinion/nothing-is-wrong-with-your-sex-drive.html|title=Nothing Is Wrong With Your Sex Drive| vauthors = Nagoski E |date=27 February 2015|access-date=31 July 2017|newspaper=The New York Times}}</ref>
	== Mechanism of action ==
	The proposed mechanism of action refers back to the Kinsey dual control model.<ref>Janssen, E, Bancroft J. The dual control model: The role of sexual inhibition & excitation in sexual arousal and behavior In Janssen, E. (Ed). (2006). The Psychophysiology of Sex. Bloomington, IN:Indiana University press.</ref> Several sex steroids, neurotransmitters, and hormones have important excitatory or inhibitory effects on the sexual response. Among the neurotransmitters, the excitatory activity is driven by dopamine and norepinephrine, while the inhibitory activity is driven by serotonin. The balance between these systems is relevant for a healthy sexual response. By modulating these neurotransmitters in selective brain areas, flibanserin, a ] agonist and ] antagonist, is likely to restore the balance between these neurotransmitter systems.<ref name=Pfaus09/><ref name=Allers10/>
			==Medical uses==
	== Clinical trials ==
			Flibanserin is used for ] among women. The onset of the flibanserin effect was seen from the first timepoint measured after 4 weeks of treatment and maintained throughout the treatment period.<ref>Simon JA, Thorp J, Katz M et al. Onset of Efficacy of Flibanserin in Premenopausal Women with Hypoactive Sexual Desire Disorder. Abstract presented at the 58th Annual Clinical Meeting of The American College of Obstetricians and Gynecologists, May 2010.</ref><ref name="Addyi FDA label" />
	Several large pivotal Phase III studies with Flibanserin were conducted in the USA, Canada and Europe.<ref name=UCM215437>http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM215437.pdf, accessed June 16th 2010</ref> They involved more than 5,000 pre-] women with generalized acquired ] (HSDD). The results of the Phase III North American Trials demonstrated that
	<blockquote>
	Although the two North American trials that used the flibanserin 100 mg qhs dose showed a
	statistically significant difference between flibanserin and placebo for the endpoint of , they
	both failed to demonstrate a statistically significant improvement on the co-primary endpoint of
	sexual desire. Therefore, neither study met the agreed-upon criteria for success in establishing the
	efficacy of flibanserin for the treatment of .<ref>page 38, http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM215437.pdf, accessed June 17th 2010</ref>
	</blockquote>
			The effectiveness of flibanserin was evaluated in three phase 3 clinical trials. Each of the three trials had two co-primary endpoints, one for satisfying sexual events (SSEs) and the other for sexual desire. Each of the 3 trials also had a secondary endpoint that measured distress related to sexual desire. All three trials showed that flibanserin produced an increase in the number of SSEs and reduced distress related to sexual desire. The first two trials used an electronic diary to measure sexual desire, and did not find an increase. These two trials also measured sexual desire using the Female Sexual Function Index (FSFI) as a secondary endpoint, and an increase was observed using this latter measure. The FSFI was used as the co-primary endpoint for sexual desire in the third trial, and again showed a statistically significant increase.<ref name="Addyi FDA label" />
	These data were first presented on November 16, 2009 at the congress of the European Society for Sexual Medicine in ].<ref>Jolly E, Clayton AH, Thorp J, et al. Efficacy of flibanserin 100 mg qhs as a potential treatment for Hypoactive Sexual Desire Disorder in pre-menopausal women. Oral presentation at the European Society of Sexual Medicine Congress, November 2009.</ref> The women receiving Flibanserin reported that the average number of times they had “satisfying sexual events” rose from 2.8 to 4.5 times a month. However, women receiving placebo reported also an increase of “satisfying sexual events” from 2.7 to 3.7 times a month. Evaluation of the overall improvement of their condition and whether the benefit was meaningful to the women, showed a significantly higher rate of a meaningful benefit in the flibanserin-treated patient group versus the placebo group.<ref>Jolly E, Thorp J, Clayton AH, et al. Patients’ Perspective of Efficacy of Flibanserin in Premenopausal Women with HSDD. Oral presentation at the 58th Annual Clinical Meeting of The American College of Obstetricians and Gynecologists, May 2010. </ref> The onset of the Flibanserin effect was seen from the first timepoint measured after 4 weeks of treatment and maintained throughout the treatment period.<ref>Simon JA, Thorp J, Katz M et al. Onset of Efficacy of Flibanserin in Premenopausal Women with Hypoactive Sexual Desire Disorder. Abstract presented at the 58th Annual Clinical Meeting of The American College of Obstetricians and Gynecologists, May 2010. </ref> The overall incidence of adverse events among women taking flibanserin was low, the majority of adverse events being mild to moderate and resolved during the treatment. The most commonly reported adverse events included dizziness, nausea, fatigue, somnolence and insomnia.<ref name=UCM215437/>
			Supportive analyses based on the patient's perspective of her symptoms at the end of the study showed that improvements in symptoms of HSDD were not only statistically significant but also clinically meaningful to women.<ref>{{cite journal | vauthors = Simon JA, Clayton AH, Kim NN, Patel S | title = Clinically Meaningful Benefit in Women with Hypoactive Sexual Desire Disorder Treated with Flibanserin | journal = Sexual Medicine | volume = 10 | issue = 1 | pages = 100476 | date = February 2022 | pmid = 34999484 | pmc = 8847820 | doi = 10.1016/j.esxm.2021.100476 }}</ref>
	== FDA approval ==
	On June 18, 2010, a federal advisory panel to the U.S. ] (FDA) unanimously voted against recommending approval of Flibanserin. Earlier in the week, a FDA staff report also recommended non-approval of the drug. While the FDA still might approve Flibanserin, in the past, negative panel votes tended to cause the FDA not to approve.<ref>{{Cite news | title = Drug for sexual desire disorder opposed by panel | newspaper = ] | date = 18 June 2010 | postscript = <!--None--> }}</ref>
	==Withdrawal==		==Side effects==
			The majority of ] were mild to moderate in severity. The most commonly reported adverse events included ], ], ], ], and ].<ref name=":0" />
	On October 8, 2010, Boehringer Ingelheim announced that it would discontinue its development of flibanserin in light of the FDA advisory panel's recommendation.<ref>{{cite news| url=http://www.reuters.com/article/idUSTRE6970TN20101008 | work=Reuters | first=Ludwig | last=Burger | title=Boehringer pulls the plug on "pink Viagra" | date=8 October 2010}}</ref>
			Drinking alcohol while on flibanserin may increase the risk of severe ]. The Addyi Prescribing Information was updated in 2019 following the FDA's review of three postmarketing alcohol interaction studies which led to increased understanding of this drug interaction. This new data led to a removal of the contraindication with alcohol and new recommendations on how to safely consume alcohol while receiving Addyi therapy.
	== See also ==
	* ]
			Current recommendations are to wait at least two hours after consuming one or two standard alcoholic drinks before taking ADDYI at bedtime or to skip their ADDYI dose if they have consumed three or more standard alcoholic drinks that evening.<ref name=":0" />
	* ]
	* ]
			==Mechanism of action==
	* ]
	* ]
			===Activity profile===
	* ]
			Flibanserin acts as a ] in the ] and the ], but only as a ] in the ] of the ]<ref name="5-ht1a efficacy">{{cite journal | vauthors = Rueter LE, de Montigny C, Blier P | title = In vivo electrophysiological assessment of the agonistic properties of flibanserin at pre- and postsynaptic 5-HT1A receptors in the rat brain | journal = Synapse | volume = 29 | issue = 4 | pages = 392–405 | date = August 1998 | pmid = 9661257 | doi = 10.1002/(SICI)1098-2396(199808)29:4<392::AID-SYN11>3.0.CO;2-T | s2cid = 23093139 }}</ref> of the ] (]) (K<sub>i</sub> = 1&nbsp;nM in ]s, but only 15–50&nbsp;nM in cortex, hippocampus and dorsal raphe)<ref name="pmid12177684" /> and, with lower ], as an ] of the ] (K<sub>i</sub> = 49 nM) and antagonist or very weak ] of the ] (K<sub>i</sub> = 4–24 nM,<ref>{{cite journal | vauthors = Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S | title = Pharmacology of flibanserin | journal = CNS Drug Reviews | volume = 8 | issue = 2 | pages = 117–142 | date = 2002 | pmid = 12177684 | pmc = 6741686 | doi = 10.1111/j.1527-3458.2002.tb00219.x }}</ref> K<sub>i</sub> = 8–650 nM <ref name="Stahl2015">{{cite journal | vauthors = Stahl SM | title = Mechanism of action of flibanserin, a multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder | journal = CNS Spectrums | volume = 20 | issue = 1 | pages = 1–6 | date = February 2015 | pmid = 25659981 | doi = 10.1017/S1092852914000832 | doi-access = free }}</ref>).<ref name="InvernizziSacchetti2003">{{cite journal | vauthors = Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R | title = Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors | journal = British Journal of Pharmacology | volume = 139 | issue = 7 | pages = 1281–1288 | date = August 2003 | pmid = 12890707 | pmc = 1573953 | doi = 10.1038/sj.bjp.0705341 }}</ref><ref name="pmid8584042">{{cite journal | vauthors = Borsini F, Giraldo E, Monferini E, Antonini G, Parenti M, Bietti G, Donetti A | title = BIMT 17, a 5-HT2A receptor antagonist and 5-HT1A receptor full agonist in rat cerebral cortex | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 352 | issue = 3 | pages = 276–282 | date = September 1995 | pmid = 8584042 | doi = 10.1007/bf00168557 | s2cid = 19340842 }}</ref><ref name="StahlSommer2011">{{cite journal | vauthors = Stahl SM, Sommer B, Allers KA | title = Multifunctional pharmacology of flibanserin: possible mechanism of therapeutic action in hypoactive sexual desire disorder | journal = The Journal of Sexual Medicine | volume = 8 | issue = 1 | pages = 15–27 | date = January 2011 | pmid = 20840530 | doi = 10.1111/j.1743-6109.2010.02032.x }}</ref> Despite the much greater affinity of flibanserin for the 5-HT<sub>1A</sub> receptor, and for reasons that are unknown (although it might be caused by the competition with endogenous serotonin), flibanserin occupies the 5-HT<sub>1A</sub> and 5-HT<sub>2A</sub> receptors '']'' with similar percentages.<ref name=pmid12177684/><ref name="pmid11243720">{{cite journal | vauthors = Scandroglio A, Monferini E, Borsini F | title = Ex vivo binding of flibanserin to serotonin 5-HT1A and 5-HT2A receptors | journal = Pharmacological Research | volume = 43 | issue = 2 | pages = 179–183 | date = February 2001 | pmid = 11243720 | doi = 10.1006/phrs.2000.0762 }}</ref> Flibanserin also has low affinity for the ] (K<sub>i</sub> = 89.3 nM) and the ] (K<sub>i</sub> = 88.3 nM), both of which it behaves as an antagonist of.<ref name="StahlSommer2011" /> Flibanserin preferentially activates 5-HT<sub>1A</sub> receptors in the ], demonstrating regional selectivity, and has been found to increase ] and ] levels and decrease ] levels in the rat prefrontal cortex, actions that were determined to be mediated by activation of the 5-HT<sub>1A</sub> receptor.<ref name="InvernizziSacchetti2003" /> As such, flibanserin has been described as a ] (NDDI).<ref name="StahlSommer2011" /><ref name="StahlStahl2008">{{cite book | vauthors = Stahl SM | title = Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications | url = https://archive.org/details/stahlsessentialp00stah | url-access = registration | access-date = 23 April 2012 | date = 17 March 2008 | publisher = Cambridge University Press | isbn = 978-0-521-67376-1 | page = }}</ref>
	* ]
	* ]
			The proposed ] refers to the Kinsey dual control model of ].<ref>Janssen, E, Bancroft J. The dual control model: The role of sexual inhibition & excitation in sexual arousal and behavior In Janssen, E. (Ed). (2006). The Psychophysiology of Sex. Bloomington, IN:Indiana University press.</ref> Various ]s, ]s, and other ]s have important ] or ] effects on the sexual response. Among neurotransmitters, excitatory activity is driven by dopamine and norepinephrine, while inhibitory activity is driven by serotonin. The balance between these systems is of significance for a normal sexual response. By modulating serotonin and dopamine activity in certain parts of the brain, flibanserin may improve the balance between these neurotransmitter systems in the regulation of sexual response.<ref name=Pfaus09>{{cite journal | vauthors = Pfaus JG | title = Pathways of sexual desire | journal = The Journal of Sexual Medicine | volume = 6 | issue = 6 | pages = 1506–1533 | date = June 2009 | pmid = 19453889 | doi = 10.1111/j.1743-6109.2009.01309.x | s2cid = 3427784 }}</ref><ref name=Allers10>{{cite journal | vauthors = Allers KA, Dremencov E, Ceci A, Flik G, Ferger B, Cremers TI, Ittrich C, Sommer B | display-authors = 6 | title = Acute and repeated flibanserin administration in female rats modulates monoamines differentially across brain areas: a microdialysis study | journal = The Journal of Sexual Medicine | volume = 7 | issue = 5 | pages = 1757–1767 | date = May 2010 | pmid = 20163532 | doi = 10.1111/j.1743-6109.2010.01763.x }}</ref>
	* ]
	* ]
			==Society and culture==
			Flibanserin was originally developed as an ],<ref name="pmid9537806">{{cite journal | vauthors = D'Aquila P, Monleon S, Borsini F, Brain P, Willner P | title = Anti-anhedonic actions of the novel serotonergic agent flibanserin, a potential rapidly-acting antidepressant | journal = European Journal of Pharmacology | volume = 340 | issue = 2–3 | pages = 121–132 | date = December 1997 | pmid = 9537806 | doi = 10.1016/S0014-2999(97)01412-X }}</ref><ref name="InvernizziSacchetti2003"/> but was found to have pro-sexual effects and was later repurposed for the treatment of HSDD.
			===Names===
			The brand name is Addyi.
			===Approval process and advocacy===
			In June 2010, a federal advisory panel to the US ] (FDA) unanimously voted against recommending approval of flibanserin, citing an inadequate risk-benefit ratio. The Committee acknowledged the validity of hypoactive sexual desire as a diagnosis, but expressed concern with the drug's side effects and insufficient evidence for efficacy, especially the drug's failure to show a statistically significant effect on the co-primary endpoint of sexual desire.<ref>{{citation |contribution=18 June 2010 meeting of the FDA Advisory Committee for Reproductive Health Drugs |title=Minutes |contribution-url=https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM248751.pdf |access-date=18 November 2015 }}</ref> Earlier in the week, a FDA staff report also recommended non-approval of the drug. Ahead of the votes, Boehringer Ingelheim had mounted a publicity campaign to promote the controversial disorder of "hypoactive sexual desire".<ref>{{Cite news |title = Drug for sexual desire disorder opposed by panel|newspaper = ]|date = 18 June 2010|url = https://www.nytimes.com/2010/06/19/business/19sexpill.html}}</ref> In 2010 the FDA issued a ], stating that the ] could not be approved in its current form. The letter cited several concerns, including the failure to demonstrate a statistical effect on the co-primary endpoint of sexual desire and overly restrictive entry criteria for the two Phase 3 trials. The Agency recommended performing a new Phase 3 trial with less restrictive entry criteria.<ref name="BRUDAC">{{Cite web|url=https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/UCM449088.pdf|title=Joint Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee (BRUDAC) and the Drug Safety and Risk Management (DSaRM) Advisory Committee|website=] }}</ref> On 8 October 2010, Boehringer announced that it would discontinue its development of flibanserin in light of the FDA's decision.<ref>{{cite news| url= https://www.reuters.com/article/idUSTRE6970TN20101008 | work=Reuters | vauthors = Burger L | title=Boehringer pulls the plug on "pink Viagra" | date=8 October 2010}}</ref>
			Sprout responded to the FDA's cited deficiencies and refiled the NDA in 2013. The submission included data from a new Phase 3 trial and several Phase 1 drug-drug interaction studies.<ref name="BRUDAC" /><ref>{{cite news| url=http://www.news-medical.net/news/20130627/Sprout-Pharmaceuticals-resubmits-flibanserin-NDA-for-treating-HSDD-in-pre-menopausal-women.aspx | title=Sprout Pharmaceuticals resubmits flibanserin NDA for treating HSDD in pre-menopausal women | date=27 June 2013}}</ref> The FDA again refused the application, citing an uncertain risk/benefit ratio. In December 2013, a Formal Dispute Resolution was filed,<ref name="sproutCon">{{cite web|url=http://sproutpharma.com/sprout-pharmaceuticals-receives-clear-guidance-from-fda-on-path-forward-to-resubmit-new-drug-application-for-flibanserin-the-first-potential-medical-treatment-for-hypoactive-sexual-desire-disorder-in/|title=ADDYI® (flibanserin) - Home|website=sproutpharma.com|access-date=31 July 2017|archive-date=10 August 2015|archive-url=https://web.archive.org/web/20150810054544/http://www.sproutpharma.com/sprout-pharmaceuticals-receives-clear-guidance-from-fda-on-path-forward-to-resubmit-new-drug-application-for-flibanserin-the-first-potential-medical-treatment-for-hypoactive-sexual-desire-disorder-in/|url-status=dead}}</ref> which contained the requirements of the FDA for further studies. These include two studies in healthy subjects to determine if flibanserin impairs their ability to drive, and to determine if it interferes with other biochemical pathways. The Agency agreed to call a new Advisory Committee meeting to consider whether the risk-benefit ratio of flibanserin was favorable after this additional data was obtained.<ref name="sproutCon"/><ref name="freep">''FDA seeks more tests on a female Viagra'', by Matthew Perrone, The Detroit Free Press, page 2A Wednesday, 12 February 2014</ref><ref>{{cite web|url=http://www.cnn.com/2014/02/11/health/female-sex-drive-drug/index.html|title=FDA: Female sex drive drug needs more research - CNN.com| vauthors = Landau E |website=CNN|date=11 February 2014|access-date=31 July 2017}}</ref> Sprout expected to resubmit the New Drug Application (NDA) in the 3rd quarter of 2014.<ref name="sproutCon"/><ref name="freep"/>
			In June 2015, the US FDA Advisory Committee, which includes the Bone, Reproductive, and Urologic Drugs Advisory Committee (BRUDAC) and the Drug Safety and Risk Management Advisory Committee (DSRM), recommended approval of the drug by 18–6, with the proviso that measures be taken to inform women of the drug's side effects.<ref>{{cite news | vauthors = Stein R |date=4 June 2015 |title=Advisers To FDA Recommend Agency Approve Drug To Boost Female Libido |url=https://www.npr.org/sections/health-shots/2015/06/04/411260331/advisers-to-fda-consider-controversial-drug-to-boost-female-libido |work=] |access-date=4 June 2015 }}</ref><ref>{{cite news|title=Critics: Women's Sex Pill Approval Vote Driven By PR, Not Science|url=https://www.forbes.com/sites/davidkroll/2015/06/07/critics-womens-sex-pill-approval-vote-driven-by-pr-not-science/|work=Forbes|date=7 June 2015}}</ref> On 18 August 2015, the FDA approved Addyi (Flibanserin) for the treatment of premenopausal women with low sexual desire that causes personal distress or relationship difficulties. The approval specified that flibanserin should not be used to treat low sexual desire caused by co-existing psychiatric or medical problems; low sexual desire caused by problems in the relationship; or low sexual desire due to medication side effects.<ref name="Addyi FDA label" />
			As of 21 August 2015, '']'' reported that Sprout Pharmaceuticals had not yet made an application to the ] for a marketing authorisation.<ref>{{cite journal | vauthors = Torjesen I |date=21 August 2015 |title=First drug to improve sexual desire in women approved in the United States |journal=] |volume=295 |issue=7878 |doi=10.1211/PJ.2015.20069201 | name-list-style=vanc }}</ref>
			===Advocacy groups===
			''Even the Score'', a coalition of women's groups brought together by a Sprout consultant, actively campaigned for the approval of flibanserin. The campaign emphasized that several approved treatments for male sexual dysfunction exist, while no such treatment for women was available.<ref>{{Cite news|title = 'Viagra for Women' Is Backed by an F.D.A. Panel|url = https://www.nytimes.com/2015/06/05/business/panel-backs-a-drug-to-increase-womens-sex-drive.html|newspaper = The New York Times|date = 4 June 2015| vauthors = Pollack A }}</ref> The group successfully obtained letters of support from the President of the ], the editor of the ], and several members of Congress.<ref>{{cite web | url = https://www.theatlantic.com/health/archive/2015/08/why-flibanserin-is-not-the-female-viagra/401789/ | title = Why Flibanserin Is Not the 'Female Viagra' | website = ] | date = 19 August 2015 }}</ref>
			Other organizations supporting the approval of flibanserin included the ], the ], the ], ], and the ].<ref>{{cite news |url=https://www.nytimes.com/2015/08/19/business/fda-approval-addyi-female-viagra.html |title=F.D.A. Approves Addyi, a Libido Pill for Women |work=The New York Times |date=18 August 2015 | vauthors = Pollack A }}</ref><ref>{{cite web |url=https://www.arhp.org/modules/press/ARHP-Commends-FDAs-Recommendation-to-Approve-Flibanserin/93 |title=Association of Reproductive Health Professionals |access-date=17 November 2015 }}</ref><ref>{{cite web |url=http://www.nclnet.org/fda_fsd_vote |title=National Consumers League |date=4 June 2015 |access-date=17 November 2015 }}</ref><ref>{{cite web |url=http://www.ashasexualhealth.org/fda-approves-first-drug-treat-low-sexual-desire-women/ |title=American Sexual Health Association |date=19 August 2015 |access-date=17 November 2015 }}</ref>
			The approval was opposed by the ], the ] and ].<ref>{{cite web |url=http://www.newsobserver.com/news/business/article31116701.html |title=Raleigh's Sprout Pharmaceuticals awaits FDA ruling on female libido drug &#124; News & Observer }}</ref> A representative of ] said "To approve this drug will set the worst kind of precedent — that companies that spend enough money can force the FDA to approve useless or dangerous drugs."<ref>{{cite web |url= https://www.minnpost.com/second-opinion/2015/06/faux-advocacy-not-science-prompted-fda-panels-ok-low-libido-drug-women-critic |title='Faux-advocacy,' not science, prompted FDA panel's OK of 'low libido' drug for women, critics charge | vauthors = Perry P |work=minnpost.com |date=8 June 2015 |access-date=18 August 2015}}</ref> An editorial in ] noted that, "Although flibanserin is not the first product to be supported by a consumer advocacy group in turn supported by pharmaceutical manufacturers, claims of gender bias regarding the FDA's regulation have been particularly noteworthy, as have the extent of advocacy efforts ranging from social media campaigns to letters from members of Congress".<ref>{{cite journal | vauthors = Gellad WF, Flynn KE, Alexander GC | title = Evaluation of Flibanserin: Science and Advocacy at the FDA | journal = JAMA | volume = 314 | issue = 9 | pages = 869–870 | date = September 2015 | pmid = 26148201 | doi = 10.1001/jama.2015.8405 }}</ref>
			The Even the Score campaign was managed by ], a public relations firm, and received funding from Sprout.<ref>{{cite web |url= http://www.politico.com/story/2015/08/sexual-politics-boosts-bid-for-pink-viagra-121310.html |title=Women's sex drug gets political hard sell | vauthors = Karlin S |work=politico.com |date=13 August 2015 |access-date=18 August 2015}}</ref>
			===Acquisition by Valeant Pharmaceuticals===
			In August 2015, ] and Sprout Pharmaceuticals announced that Valeant will acquire Sprout, on a debt-free basis, for approximately $1 billion in cash, plus a share of future profits based upon the achievement of certain milestones.<ref>{{Cite web |url=http://ir.valeant.com/investor-relations/news-releases/news-release-details/2015/Valeant-Pharmaceuticals-To-Acquire-Sprout-Pharmaceuticals/default.aspx |title=Valeant - Valeant Pharmaceuticals to Acquire Sprout Pharmaceuticals |access-date=25 October 2015 |archive-url=https://web.archive.org/web/20150822221318/http://ir.valeant.com/investor-relations/news-releases/news-release-details/2015/Valeant-Pharmaceuticals-To-Acquire-Sprout-Pharmaceuticals/default.aspx |archive-date=22 August 2015 |url-status=dead }}</ref>
			==Reception==
			The initial response since the 2015 introduction of flibanserin to the U.S. market was slow with 227 prescriptions written during the first three weeks.<ref name=bb>{{cite web| url=https://www.bloomberg.com/news/articles/2015-11-17/valeant-s-newest-problem-the-female-libido-pill-isn-t-selling| vauthors = Edney A, Colbey L | title=The Female Libido Pill Is No Viagra |publisher=]| date=17 November 2015 |access-date=18 November 2015}}</ref> The slow response may be related to a number of factors: physicians require about 10 minutes of online training to get certified; the medication has to be taken daily and costs about US$400 per month;<ref>{{cite web| url=https://www.goodrx.com/addyi| title=Addyi Flibanserin |publisher=]}}</ref> and questions about the drug's efficacy and need.<ref name=bb/> Prescriptions for the drug continue to be few with less than 4,000 being made as of February 2016.<ref>{{cite news| vauthors = Thomas K |title=The Female Viagra, Undone by a Drug Maker's Dysfunction|url=https://www.nytimes.com/2016/04/10/business/female-viagra-addyi-valeant-dysfunction.html|access-date=9 April 2016|work=The New York Times|date=9 April 2016 }}</ref>
	== References ==		== References ==
	{{Reflist}}		{{reflist}}
	== External links ==		== Further reading ==
			{{refbegin}}
	*
			* {{cite book | title=Medical Genetics Summaries | chapter=Flibanserin Therapy and CYP2C19 Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK546788/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=6 | publisher=] (NCBI) | date=September 2019 | pmid=31550099 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }}
	*{{cite journal |author=Marazziti D, Palego L, Giromella A, ''et al.'' |title=Region-dependent effects of flibanserin and buspirone on adenylyl cyclase activity in the human brain |journal=Int. J. Neuropsychopharmacol. |volume=5 |issue=2 |pages=131–40 |year=2002 |month=June |pmid=12135537 |doi=10.1017/S1461145702002869 |url=http://journals.cambridge.org/abstract_S1461145702002869}}
			* {{cite thesis | vauthors = Aubert Y | title=Sex, aggression and pair-bond : a study on the serotonergic regulation of female sexual function in the marmoset monkey | publisher=Leiden University | date=December 2012 | hdl=1887/20268 | isbn=9789461821959 }}
	*{{cite journal |author=Podhorna J, Brown RE |title=Flibanserin has anxiolytic effects without locomotor side effects in the infant rat ultrasonic vocalization model of anxiety |journal=Br J Pharmacol |volume=130 |issue=4 |pages=739–746 |year=2000 |month=June |pmid=10864879 |pmc=1572126 |doi=10.1038/sj.bjp.0703364 |url=http://www3.interscience.wiley.com/journal/121664068/abstract}}
	*{{cite journal |doi=10.1016/S0924-977X(99)00056-5 |author=Brambilla A, Baschirotto A, Grippa N, Borsini F |title=Effect of flibanserin (BIMT 17), fluoxetine, 8-OH-DPAT and buspirone on serotonin synthesis in rat brain |journal=Eur Neuropsychopharmacol |volume=10 |issue=1 |pages=63–7 |year=1999 |month=December |pmid=10647099 |url=http://linkinghub.elsevier.com/retrieve/pii/S0924-977X(99)00056-5}}		* {{cite journal | vauthors = Marazziti D, Palego L, Giromella A, Mazzoni MR, Borsini F, Mayer N, Naccarato AG, Lucacchini A, Cassano GB | display-authors = 6 | title = Region-dependent effects of flibanserin and buspirone on adenylyl cyclase activity in the human brain | journal = The International Journal of Neuropsychopharmacology | volume = 5 | issue = 2 | pages = 131–140 | date = June 2002 | pmid = 12135537 | doi = 10.1017/S1461145702002869 | doi-access = free }}
			* {{cite journal | vauthors = Podhorna J, Brown RE | title = Flibanserin has anxiolytic effects without locomotor side effects in the infant rat ultrasonic vocalization model of anxiety | journal = British Journal of Pharmacology | volume = 130 | issue = 4 | pages = 739–746 | date = June 2000 | pmid = 10864879 | pmc = 1572126 | doi = 10.1038/sj.bjp.0703364 }}
			* {{cite journal | vauthors = Brambilla A, Baschirotto A, Grippa N, Borsini F | title = Effect of flibanserin (BIMT 17), fluoxetine, 8-OH-DPAT and buspirone on serotonin synthesis in rat brain | journal = European Neuropsychopharmacology | volume = 10 | issue = 1 | pages = 63–67 | date = December 1999 | pmid = 10647099 | doi = 10.1016/S0924-977X(99)00056-5 | s2cid = 1470166 }}
			{{refend}}
			== External links ==
			* {{cite web |title=FDA orders important safety labeling changes for Addyi|url=https://www.fda.gov/news-events/press-announcements/fda-orders-important-safety-labeling-changes-addyi|date=11 April 2019|work=U.S. ] (FDA) }}
			* {{cite news |title=The Company Behind 'Female Viagra' Just Raised $20 Million in Funding|url=https://fortune.com/2019/09/04/female-viagra-addyi-venture-funding/|date=4 September 2019|work=Fortune}}
			* {{cite web | title=The Women's Libido Pill Is Back, and So Is the Controversy | website=Bloomberg | date=13 June 2018 | url=https://www.bloomberg.com/news/features/2018-06-13/the-women-s-libido-pill-is-back-and-so-is-the-controversy }}
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