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Flibanserin

PubChem CID
6918248
Structure
Flibanserin_small.png
Flibanserin_3D_Structure.png
Molecular Formula
Synonyms
  • Flibanserin
  • 167933-07-5
  • Bimt-17
  • Addyi
  • Bimt 17
Molecular Weight
390.4 g/mol
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Dates
  • Create:
    2006-07-28
  • Modify:
    2025-01-18
Description
Flibanserin is an N-alkylpiperazine that is 1-[2-(1,3-dihydro-2-oxobenzimidazol-1-yl)ethyl]piperazine in which the remaining amino proton is replaced by a 3-(trifluoromethyl)phenyl group. A multifunctional serotonin agonist and antagonist which is used for the treatment of pre-menopausal women with hypoactive sexual desire disorder. It has a role as a serotonergic agonist, a serotonergic antagonist and an antidepressant. It is a member of benzimidazoles, a N-arylpiperazine, a N-alkylpiperazine and an organofluorine compound.
Flibanserin is the first drug to be approved for hypoactive sexual desire disorder (HSDD) in premenopausal women by the FDA in August 2015. It was originally developed as an antidepressant medication by Boehringer Ingelheim, but showed lack of efficacy in trials and was further developed as a hypoactive sexual disorder drug by Sprout Pharmaceuticals. Flibanserin's mechanism of action is attributed to its high affinity for 5-HTA1 and 5-HTA2 receptors, displaying agonist activity on 5-HTA1 and antagonist on 5-HTA2, resulting in lowering of serotonin in the brain as well as an effect on increasing norepinephrine and dopamine neurotransmitters.
The mechanism of action of flibanserin is as a P-Glycoprotein Inhibitor.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Flibanserin.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

3-[2-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]ethyl]-1H-benzimidazol-2-one
Computed by Lexichem TK 2.7.0 (PubChem release 2024.11.20)

2.1.2 InChI

InChI=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)
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.3 InChIKey

PPRRDFIXUUSXRA-UHFFFAOYSA-N
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.4 SMILES

C1CN(CCN1CCN2C3=CC=CC=C3NC2=O)C4=CC=CC(=C4)C(F)(F)F
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C20H21F3N4O
Computed by PubChem 2.2 (PubChem release 2024.11.20)

2.3 Other Identifiers

2.3.1 CAS

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 ChEBI ID

2.3.5 ChEMBL ID

2.3.6 DrugBank ID

2.3.7 DSSTox Substance ID

2.3.8 HMDB ID

2.3.9 KEGG ID

2.3.10 Metabolomics Workbench ID

2.3.11 NCI Thesaurus Code

2.3.12 Nikkaji Number

2.3.13 PharmGKB ID

2.3.14 Pharos Ligand ID

2.3.15 RXCUI

2.3.16 Wikidata

2.3.17 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 1-(2-(4-(3-trifluoromethylphenyl)piperazin-1-yl)ethyl)benzimidazol(1H)-2-one
  • Addyi
  • BIMT 17
  • BIMT-17
  • flibanserin

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
390.4 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
XLogP3-AA
Property Value
3.3
Reference
Computed by XLogP3 3.0 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Acceptor Count
Property Value
6
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Rotatable Bond Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Exact Mass
Property Value
390.16674579 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Monoisotopic Mass
Property Value
390.16674579 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Topological Polar Surface Area
Property Value
38.8 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Heavy Atom Count
Property Value
28
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
550
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Color / Form

White, to off-white powder
US NLM; DailyMed. Current Medical Information. US Natl Lib Med, Natl Inst Health, Health Human Serv. Available from, as of Oct 15, 2015: https://dailymed.nlm.nih.gov/dailymed/about.cfm

3.2.2 Solubility

Insoluble in water
US NLM; DailyMed. Current Medical Information. US Natl Lib Med, Natl Inst Health, Health Human Serv. Available from, as of Oct 15, 2015: https://dailymed.nlm.nih.gov/dailymed/about.cfm
Sparingly soluble in methanol, ethanol, acetonitrile, toluene; solulble in acetone; freely soluble in chloroform; very soluble in methylene chloride
US NLM; DailyMed. Current Medical Information. US Natl Lib Med, Natl Inst Health, Health Human Serv. Available from, as of Oct 15, 2015: https://dailymed.nlm.nih.gov/dailymed/about.cfm

3.2.3 Stability / Shelf Life

Stable under recommended storage conditions.
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html

3.2.4 Other Experimental Properties

Crystals from isopropanol; MP 230-231 °C/Filbanserin hydrochloride/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 752
SMILES C(F)(F)(F)c1cc(N2CCN(CCN3c4c(cccc4)NC3=O)CC2)ccc1
US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 15, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
Pharmaceuticals -> Genito-urinary system and sex hormones -> Other gynecologicals
S92 | FLUOROPHARMA | List of ~340 ATC classified fluoro-pharmaceuticals | DOI:10.5281/zenodo.5979646
3.3.1.1 Human Drugs
Human drug -> Active ingredient (FLIBANSERIN)
Human drug -> Prescription
Paediatric drug

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 13C NMR Spectra

Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 2
Technique
GC/MS
Source of Spectrum
DigiLab GmbH (C) 2024
Copyright
Copyright © 2024 DigiLab GmbH and Wiley-VCH GmbH. All Rights Reserved.
Thumbnail
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2 of 2
Technique
GC/MS
Source of Spectrum
DigiLab GmbH (C) 2024
Copyright
Copyright © 2024 DigiLab GmbH and Wiley-VCH GmbH. All Rights Reserved.
Thumbnail
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6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

For the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women.
Hypoactive Sexual Desire Disorder in Women

7.2 LiverTox Summary

Flibanserin is a serotonergic antidepressant used to treat hypoactive sexual desire disorder. Flibanserin has been associated with a low rate of minor serum aminotransferase elevations during treatment, but has not been linked to instances of clinically apparent acute liver injury.

7.3 Drug Classes

Antidepressant Agents

7.4 FDA Medication Guides

Drug
Active Ingredient
FLIBANSERIN
Form;Route
TABLET;ORAL
Company
SPROUT PHARMS
Date
09/29/2021

7.5 FDA Approved Drugs

7.6 FDA Orange Book

7.7 FDA National Drug Code Directory

7.8 Drug Labels

Drug and label
Active ingredient and drug

7.9 Clinical Trials

7.9.1 ClinicalTrials.gov

7.9.2 EU Clinical Trials Register

7.10 EMA Drug Information

Type
Paediatric investigation
Active Substance
Therapeutic Area
Endocrinology-Gynaecology-Fertility-Metabolism
Drug Form
Film-coated tablet
Administration Route
Oral use
Decision Type
W: decision granting a waiver in all age groups for all conditions or indications
Decision Date
2008-04-28

7.11 Therapeutic Uses

/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Flibanserin is included in the database.
NIH/NLM; ClinicalTrials.Gov. Available from, as of September 30, 2015: https://clinicaltrials.gov/search/intervention=FLIBANSERIN%20OR%20BIMT-17
Addyi is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to: A co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance. Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner. /Included in US product label/
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
EXPL THER A central problem in the treatment of Parkinson's disease (PD) is the development of motor disturbances like L-DOPA-induced dyskinesia (LID) after long-term treatment. Preclinical and clinical studies demonstrated that serotonin 5-HT(1A) receptor agonists attenuate this disabling motor side effect. The aim of this study was to investigate the ability of flibanserin compared to buspirone to attenuate L-DOPA-sensitized contraversive circling in hemiparkinsonian rats, which is an animal model of LID. Both drugs have a preferential affinity for the serotonin 5-HT(1A) receptors. Buspirone was in comparison because it was expected to have an effect in this model. Unilaterally 6-hydroxydopamine lesioned rats were treated twice daily intraperitoneally (ip) with L-DOPA methylester (12.5 mg/kg) and benserazide (3.25 mg/kg) for 21 days (on days 1, 3, 5, 8, 11, 14, 17 and 21). On day 24, L-DOPA-sensitized rats were treated ip 5 min prior to administration of L-DOPA methyl ester and benserazide with either saline (controls), 2.5, 5 and 10 mg/kg buspirone or flibanserin. Acute administration of both flibanserin and buspirone, dose dependently, attenuated the increased contraversive circling. An almost complete inhibition of the turning response was observed at 5 mg/kg buspirone and 10 mg/kg flibanserin. The current preclinical findings further implicate the 5-HT(1A) receptor as a promising therapeutic target for the reduction of LID and predict a potential efficacy of flibanserin in the treatment of LID in PD.
Gerlach M et al; J Neural Transm 118(12): 1727-32 (2011).

7.12 Drug Warnings

/BOX WARNING/ The use of Addyi in patients with hepatic impairment increases flibanserin concentrations, which can cause severe hypotension and syncope. Therefore, Addyi is contraindicated in patients with hepatic impairment. Inhibitors are contraindicated in patients taking Addyi.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
/BOX WARNING/ The concomitant use of Addyi and moderate or strong CYP3A4 inhibitors increase s flibanserin concentrations, which can cause severe hypotension and syncope. Therefore, the use of moderate or strong CYP3A4 inhibitors is contraindicated in patients taking Addyi.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
/BOX WARNING/ The use of Addyi and alcohol increases the risk of severe hypotension and syncope. Therefore, alcohol use is contraindicated in patients taking Addyi. Before prescribing Addyi, assess the likelihood of the patient abstaining from alcohol, taking into account the patient's current and past drinking behavior, and other pertinent social and medical history. Counsel patients who are prescribed Addyi about the importance of abstaining from alcohol use. Because of the increased risk of hypotension and syncope due to an interaction with alcohol, Addyi is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Addyi REMS Program.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
Addyi can cause CNS depression (e.g., somnolence, sedation). In five 24-week, randomized, placebo controlled, double-blind trials of premenopausal women with hypoactive sexual desire disorder (HSDD), the incidence of somnolence, sedation or fatigue was 21% and 8% in patients treated with 100 mg Addyi once daily at bedtime and placebo, respectively. The risk of CNS depression is increased if Addyi is taken during waking hours, or if Addyi is taken with alcohol or other CNS depressants, or with medications that increase flibanserin concentrations, such as CYP3A4 inhibitors.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
For more Drug Warnings (Complete) data for Flibanserin (9 total), please visit the HSDB record page.

8 Pharmacology and Biochemistry

8.1 FDA Pharmacological Classification

1 of 2
FDA UNII
37JK4STR6Z
Active Moiety
FLIBANSERIN
Pharmacological Classes
Mechanisms of Action [MoA] - P-Glycoprotein Inhibitors
FDA Pharmacology Summary
The mechanism of action of flibanserin is as a P-Glycoprotein Inhibitor.
2 of 2
Non-Proprietary Name
FLIBANSERIN
Pharmacological Classes
P-Glycoprotein Inhibitors [MoA]

8.2 ATC Code

G - Genito urinary system and sex hormones

G02 - Other gynecologicals

G02C - Other gynecologicals

G02CX - Other gynecologicals

G02CX02 - Flibanserin

8.3 Absorption, Distribution and Excretion

Absorption
Flibanserin has an absolute oral availability of 33%.
Route of Elimination
Elimination via feces (51%) and urine (44%) following a single oral 50 mg dose of flibanserin solution.
Approximately 98% of the drug is bound to human serum proteins, mainly to albumin.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
Food increased the extent of absorption and slowed the rate of absorption of a 50 mg dose of flibanserin (one half the recommended dosage). Low-, moderate-, and high-fat meals increased flibanserin AUC0-inf by 1.18-, 1.43-, and 1.56-fold; increased Cmax by 1.02-, 1.13-, and 1.15-fold; and prolonged median Tmax to 1.5, 0.9, 1.8 hours from 0.8 hours under fasted conditions, respectively.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
Following oral ministration of a single 100 mg dose of flibanserin in healthy premenopausal women (N=8), mean (SD) Cmax was 419 (206) ng/mL and mean (SD) AUC0-inf was 1543 (511) ng*hr/mL. Median (range) time to reach Cmax was 0.75 (0.75 to 4.0) hours. Absolute bioavailability of flibanserin following oral dosing is 33%.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
/MILK/ Flibanserin is excreted in rat milk. It is unknown whether flibanserin is present in human milk, ... .
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394

8.4 Metabolism / Metabolites

Metabolism is primarily via CYP3A4, slightly CYP2C19. Minimal involvement of CYP1A2, CYP2B6, CYP2C8, CYP2C9 or CYP2D6. At least 35 metabolites of flibanserin are produced, 2 of which reach plasma concentrations as high as parent drug, however they are pharmacologically inactive.
Flibanserin is primarily metabolized by CYP3A4 and, to a lesser extent, by CYP2C19. Based on in vitro and/or in vivo data, CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2D6 contribute minimally to the metabolism of flibanserin. After a single oral solution dose of 50 mg 14C-radiolabeled flibanserin, 44% of the total 14C-flibanserin related radioactivity was recovered in urine, and 51% was recovered in feces. Flibanserin is extensively metabolized to at least 35 metabolites, most of them occurring in low concentrations in plasma. Two metabolites could be characterized that showed plasma concentrations similar to that achieved with flibanserin: 6,21-dihydroxy-flibanserin-6,21-disulfate and 6-hydroxy-flibanserin-6-sulfate. These two metabolites are inactive.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394

8.5 Biological Half-Life

≈11 hours
Flibanserin has a mean terminal half-life of approximately 11 hours.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394

8.6 Mechanism of Action

Flibansetrin has high affinity for serotonin receptors in the brain: it acts as an agonist on 5-HT1A and an antagonist on 5-HT2A. In vivo, flibanserin binds equally to 5-HT1A and 5-HT2A receptors. However, under higher levels of brain 5-HT (i.e., under stress), flibanserin may occupy 5-HT2A receptors in higher proportion than 5-HT(1A) receptors. It may also moderately antagonize D4 (dopamine) receptors and 5-HT2B and 5-HTB2C. Its action on neurotransmitter receptors may contribute to reduction in serotonin levels and increase in dopamine and norepinephrine levels, all of which may play part in reward processing.
Flibanserin has preferential affinity for serotonin 5-HT(1A), dopamine D(4k), and serotonin 5-HT(2A) receptors. In vitro and in microiontophoresis, flibanserin behaves as a 5-HT(1A) agonist, a very weak partial agonist on dopamine D(4) receptors, and a 5-HT(2A) antagonist. In vivo flibanserin binds equally to 5-HT(1A) and 5-HT(2A) receptors. However, under higher levels of brain 5-HT (i.e., under stress), flibanserin may occupy 5-HT(2A) receptors in higher proportion than 5-HT(1A) receptors. The effects of flibanserin on adenylyl cyclase are different from those of buspirone and 8-OH-DPAT, two other purported 5-HT(1A) receptor agonists. Flibanserin reduces neuronal firing rate in cells of the dorsal raphe, hippocampus, and cortex with the CA1 region being the most sensitive in the brain. Flibanserin-induced reduction in firing rate in the cortex seems to be mediated through stimulation of postsynaptic 5-HT(1A) receptors, whereas the reduction of the number of active cells seems to be mediated through dopamine D(4) receptor stimulation. Flibanserin quickly desensitizes somatic 5-HT autoreceptors in the dorsal raphe and enhances tonic activation of postsynaptic 5-HT(1A) receptors in the CA3 region. Flibanserin preferentially reduces synthesis and extracellular levels of 5-HT in the cortex, where it enhances extracellular levels of NE and DA. Flibanserin displays antidepressant-like activity in most animal models sensitive to antidepressants. Such activity, however, seems qualitatively different from that exerted by other antidepressants. Flibanserin seems to act via direct or indirect stimulation of 5-HT(1A), DA, and opioid receptors in those animal models. Flibanserin does not display consistent effects in animal models of anxiety and seems to exert potential antipsychotic effects. Flibanserin may induce some sedation but does not induce observable toxic effects at pharmacologically relevant doses.
Borsini F et al; CNS Drug Rev 8(2): 117-42 (2002).
Flibanserin is a novel pharmacologic agent in late-stage clinical testing for hypoactive sexual desire disorder (HSDD) in premenopausal women. A literature review was conducted of all published works on flibanserin and on related studies of serotonin (5-HT)(1A) receptors and 5-HT(2A) receptors, including their actions on monoamines and on sexual function. At clinically relevant doses, flibanserin acts predominantly at 5-HT(1A) receptors as an agonist and secondarily at 5-HT(2A) receptors as an antagonist. Additional binding actions within an order of magnitude of its 5-HT(1A) affinity, which are not likely to be clinically relevant, include weaker antagonist actions at 5-HT(2C) and 5-HT(2B) receptors, and less defined activity at dopamine (DA) D4 receptors. The 5-HT(1A) actions of flibanserin are only seen postsynaptically, which is unlike other agents such as buspirone that act at presynaptic 5-HT(1A) receptors. Furthermore, the postsynaptic actions of chronic flibanserin administration appear to demonstrate a preference for some populations of postsynaptic 5-HT receptors, particularly those that are located on the prefrontal cortex (PFC) pyramidal neurons, which regulate monoamine release in certain selective brain regions. The regional selectivity of flibanserin results in a unique pattern of monoamine modulation. Sustained increases in baseline of DA and norepinephrine (NE) are observed in the PFC, and flibanserin dosing increases DA and NE levels above the basal changes. Conversely, flibanserin induces transient decreases in 5-HT levels in some brain areas such as the PFC, nucleus accumbens, and hypothalamus, but not in other brain areas such as the hippocampus. Therefore, since DA and NE are excitatory and 5-HT is inhibitory to sexual desire and arousal, it is tempting to postulate that the actions of flibanserin on serotonin receptors at the PFC pyramidal neurons, resulting in increased DA and NE yet reduced 5-HT in the PFC, are the mechanistic underpinnings of enhancing sexual desire in HSDD.
Stahl SM et al; J Sex Med 8(1):15-27 (2011).
In vitro, flibanserin demonstrated high affinity for the following serotonin (5-hydroxytryptamine or 5-T) receptors: agonist activity at 5-HT1A and antagonist activity at 5-HT2A. Flibanserin also has moderate antagonist activities at the 5-HT2B, 5-HT2C, and dopamine D4 receptors.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394

9 Use and Manufacturing

9.1 Uses

MEDICATION

9.1.1 Use Classification

Human Drugs -> EU pediatric investigation plans
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

9.2 Methods of Manufacturing

Preparation: M. Turconi et al., European Patent Office patent 526434; G. Bietti et al., USA patent 5576318 (1993, 1996 both to Boehringer Ingelheim).
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 752

9.3 Formulations / Preparations

Oral: Tablets Addyi (flibanserin) 100 mg
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

1 of 2
View All
Pictogram(s)
Acute Toxic
Irritant
Signal
Danger
GHS Hazard Statements

H301 (92.7%): Toxic if swallowed [Danger Acute toxicity, oral]

H315 (95.1%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (95.1%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (92.7%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P261, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 41 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

10.1.2 Hazard Classes and Categories

Acute Tox. 3 (92.7%)

Skin Irrit. 2 (95.1%)

Eye Irrit. 2 (95.1%)

STOT SE 3 (92.7%)

10.2 Fire Fighting

10.2.1 Fire Fighting Procedures

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html
Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html

10.3 Accidental Release Measures

10.3.1 Cleanup Methods

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html

10.3.2 Disposal Methods

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html

10.3.3 Preventive Measures

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html
Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html

10.4 Handling and Storage

10.4.1 Storage Conditions

Store at 25 °C (77 °F); excursions permitted to 15 deg - 30 °C (59 deg - 86 °F).
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
Conditions for safe storage, including any incompatibilities Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature 2 - 8 degrees C.
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html

10.5 Exposure Control and Personal Protection

10.5.1 Personal Protective Equipment (PPE)

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html
Body Protection: Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html
Skin protection: Handle with gloves.
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html

10.6 Stability and Reactivity

10.6.1 Hazardous Reactivities and Incompatibilities

Incompatible materials: Strong oxidizing agents
Sigma-Aldrich; Material Safety Data Sheet for Flibanserin, Product Number: SML0797, Version 5.2 (Revision Date 05/26/2014). Available from, as of November 03, 2015: https://www.sigmaaldrich.com/safety-center.html

10.7 Regulatory Information

10.7.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including flibanserin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of September 30, 2015: https://www.fda.gov/cder/ob/

11 Toxicity

11.1 Toxicological Information

11.1.1 Toxicity Summary

IDENTIFICATION AND USE: Flibanserin (trade name Addyi) is a non-hormonal drug approved for the treatment of generalized hypoactive sexual desire disorder (HSDD) in pre- and postmenopausal women. HUMAN EXPOSURE AND TOXICITY: The adverse event profile of flibanserin is similar to that of other centrally acting drugs. In human exposure studies, the most common reported adverse event was sedation/ drowsiness. Dizziness, nausea, fatigue and somnolence were also reported. Flibanserin can cause CNS depression. The use of flibanserin in patients with hepatic impairment increases flibanserin concentrations, which can cause severe hypotension and syncope. Hypotension and syncope are also an increased risk for patients taking moderate to strong CYP3A4 inhibitors. Concomitant alcohol use also increases the risk of severe hypotension and syncope in patients taking flibanserin. Flibanserin has preferential affinity for serotonin 5-HT(1A), dopamine D(4k), and serotonin 5-HT(2A) receptors. In vitro and in microiontophoresis, flibanserin behaves as a 5-HT(1A) agonist, a very weak partial agonist on dopamine D(4) receptors, and a 5-HT(2A) antagonist. Flibanserin does not display consistent effects in animal models of anxiety and seems to exert potential antipsychotic effects. Flibanserin may induce some sedation but does not induce observable toxic effects at pharmacologically relevant doses. ANIMAL STUDIES: In carcinogenicity studies, mammary tumors were observed in female mice. Hepatocellular carcinomas were reported in female and male mice, however, these effects were only noted in animals exposed to flibanserin at 3-10 x the clinically recommended dose.

11.1.2 Hepatotoxicity

In placebo controlled trials, liver test abnormalities were no more common with flibanserin than with placebo treatment, and what abnormalities occurred were mild and resolved spontaneously, usually without need for dose interruption. During these premarketing clinical trials and since its more widespread clinical availability, no instances of acute liver injury with jaundice have been reported attributable to flibanserin. However, the total clinical experience with flibanserin use has been limited. Many other serotonergic agents, such as the SSRIs, have been implicated in rare instances of clinically apparent liver injury. The latency to onset is typically 1 to 8 weeks and the pattern of enzyme elevations varies, ranging from cholestatic to hepatocellular. Mild signs and symptoms of hypersensitivity (rash, fever, eosinophilia) are common, but usually not prominent. Autoantibody formation is rare. The course is generally self-limited and mild-to-moderate in severity, but fatalities have been reported with some SSRIs. However, flibanserin itself has not been implicated in similar cases.

Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).

11.1.3 Interactions

The concomitant use of Addyi with digoxin, a drug that is transported by P-glycoprotein (P-gp), increases the digoxin concentration. This may lead to digoxin toxicity.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
In this study the functional interaction of the antidepressant drugs amitriptyline, mianserin, maprotiline, imipramine, fluoxetine and the putative antidepressant drug flibanserin has been studied on 5-HT7-mediated responses to 5-carboxamidotryptamine (5-CT) in the guinea-pig ileum. 5-CT induced a concentration-dependent inhibition of the contractile response to substance P (100 nM). Except for fluoxetine and flibanserin, all the antidepressants antagonized by different degrees the 5-CT inhibitory response with the following rank affinity order: mianserin > maprotiline > imipramine > amitriptyline. Mianserin was the only antidepressant to show a profile of competitive antagonism at 5-HT7 receptors in a tenfold range of concentrations (0.1-1 microM), with an affinity (pA2) value of 8.1 +/- 0.6. The antagonism of the other antidepressants was not concentration-dependent (amitriptyline) or was associated with slight or moderate reduction of the maximal 5-CT response (imipramine or maprotiline). The apparent affinity (pKB) values were: amitriptyline, 7.0 +/- 0.2; maprotiline, 7.3 +/- 0.6; imipramine, 7.2 +/- 0.4. Our results show that various +antidepressant drugs belonging to different chemical classes behave as antagonists at enteric 5-HT7 receptors through competitive or allosteric mechanisms. This evidence extends our previous findings demonstrating the interaction of antidepressants with other 5-HT receptors, namely 5-HT3 and 5-HT4 receptors.
Lucchelli A et al; Naunyn Schmiedebergs Arch Pharmacol 362(3): 284-9 (2000).
The concomitant use of Addyi with CYP3A4 inducers substantially decreases flibanserin exposure compared to the use of Addyi alone. Examples of CYP3A4 inducers: Carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapetine, St. John's Wort.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
The concomitant use of Addyi with strong CYP2C19 inhibitors may increase flibanserin exposure which may increase the risk of hypotension, syncope, and CNS depression. Examples of strong CYP2C19 inhibitors: Proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, antifungals.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
For more Interactions (Complete) data for Flibanserin (10 total), please visit the HSDB record page.

11.1.4 Antidote and Emergency Treatment

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160-1

11.1.5 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ Flibanserin is being developed for treating hypoactive sexual desire disorder in women; the main side effect is sedation. The analysis objective was to relate flibanserin plasma concentrations with acute sedative effects using a population pharmacokinetic/pharmacodynamic (PK/PD) model. The population model was developed with NONMEM based on data from 24 healthy volunteers. "Drowsiness" was serially assessed by a Visual Analogue Scale (VAS) on a baseline day and after morning oral administration of 100 mg flibanserin together with PK sampling. PK was best described by a three-compartment disposition model and transit compartments accounting for the lag time in absorption. VAS "drowsiness" baseline profiles were modeled using linear splines with three breakpoints located at clock times at first and last observation, and at the median of the observation time across subjects. The drug effect followed a sigmoidal E(MAX) model using predicted effect site concentrations (C(e)). The VAS vs. C(e) relationship was very steep and effect site and plasma concentration-time profiles were very similar thus suggesting little delay between the occurrence of maximum flibanserin plasma concentrations and drowsiness. At effect site concentrations lower than approximately 200 ng/mL that are reached approximately 4 hr after administration, flibanserin shows hardly any effect on the VAS "drowsiness" scale.
Troconiz IF et al; Pharm Res 29 (6): 1518-29 (2012)
/OTHER TOXICITY INFORMATION/ Flibanserin works by correcting an imbalance of the levels of the neurotransmitters that affect sexual desire. More specifically, flibanserin increases dopamine and norepinephrine, both responsible for sexual excitement, and decreases serotonin, responsible for sexual inhibition.
Reviriego C; Drugs Today (Barc) 50(8): 549-56 (2014).

11.1.6 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ There were no significant increases in tumor incidence in a two year carcinogenicity study conducted in rats with dietary administration of 0, 10, 30 and 100 mg/kg/day flibanserin (up to 5-8 times human exposure at the recommended clinical dose).
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ A two-year carcinogenicity study was conducted in mice with dietary administration of 0, 10, 80, 200 and 1000/1200 mg/kg/day of flibanserin. Statistically significant increases in combined mammary tumors (adenocanthomas and adenocarcinomas) were observed in female mice administered flibanserin at doses of 200 and 1200 mg/kg/day (exposures, based on AUC, were 3 and 10 times clinical exposures at the recommended clinical dose). No increases in mammary tumors were observed in male mice. Statistically significant increases were also seen for combined hepatocellular adenomas/carcinomas in female mice treated with flibanserin 1200 mg/kg/day and for hepatocellular carcinomas in male mice treated with flibanserin 1000 mg/kg/day (exposures, based on AUC, were 8 times the clinical exposure at the recommended clinical dose).
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Female and male rats were administered flibanserin 14 and 28 days before mating, respectively, to assess for potential effects on fertility and early reproductive performance. Flibanserin slightly increased the duration of the estrus cycle but had no adverse effects on fertility or early embryonic development at doses up to 200 mg/kg/day (~20 times human exposure at the recommended clinical dose).
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Pregnant rats were administered flibanserin at doses of 0, 20, 80 and 200 mg/kg/day (3, 15 and approximately 20 times clinical exposures at the recommended human dose) from day 6 of pregnancy until day 21 of lactation to assess for effects on peri- and postnatal development. The highest dose was associated with clinical signs of toxicity in pregnant and lactating rats. All doses resulted in sedation and decreases in body weight gain during pregnancy. Flibanserin prolonged gestation in some dams in all dose groups and decreased implantations, number of fetuses and fetal weights at 200 mg/kg/day. Dosing dams with 200 mg/kg also decreased pup weight gain and viability during the lactation period and delayed opening of the vagina and auditory canals. Flibanserin had no effects on learning, reflexes, fertility or reproductive capacity of the F1 generation. The no adverse effect level for maternal toxicity and peri/postnatal effects was 20 mg/kg/day.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
For more Non-Human Toxicity Excerpts (Complete) data for Flibanserin (9 total), please visit the HSDB record page.

11.1.7 Populations at Special Risk

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.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394
The use of Addyi in patients with any degree of hepatic impairment significantly increases flibanserin concentrations, which can lead to hypotension and syncope. Therefore, the use of Addyi is contraindicated in patients with hepatic impairment.
NIH; DailyMed. Current Medication Information for Addyi (Flibanserin) Tablet, Film Coated (Updated: August 2015). Available from, as of November 20, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3819daf3-e935-2c53-c527-e1d57922f394

11.1.8 Protein Binding

~98%, highly bound to proteins (mostly albumin) in serum.

12 Associated Disorders and Diseases

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Springer Nature References

13.4 Thieme References

13.5 Chemical Co-Occurrences in Literature

13.6 Chemical-Gene Co-Occurrences in Literature

13.7 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 WIPO PATENTSCOPE

14.3 FDA Orange Book Patents

14.4 Chemical Co-Occurrences in Patents

14.5 Chemical-Disease Co-Occurrences in Patents

14.6 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Chemical-Target Interactions

15.2 Drug-Drug Interactions

15.3 Drug-Food Interactions

  • Avoid alcohol. Avoid alcohol. Ingesting alcohol may increase the CNS depressant and hypotensive effects of flibanserin. If you have consumed two drinks, wait two hours before taking flibanserin. Do not take flibanserin if you have consumed more than three drinks.
  • Avoid grapefruit products.
  • Avoid St. John's Wort.
  • Take with or without food. Taking flibanserin with food (especially a high-fat meal) may increase its AUC, Cmax, and Tmax.

16 Biological Test Results

16.1 BioAssay Results

17 Classification

17.1 MeSH Tree

17.2 NCI Thesaurus Tree

17.3 ChEBI Ontology

17.4 KEGG: USP

17.5 KEGG: ATC

17.6 KEGG: Target-based Classification of Drugs

17.7 KEGG: Drug Groups

17.8 WHO ATC Classification System

17.9 FDA Pharm Classes

17.10 ChemIDplus

17.11 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

17.12 ChEMBL Target Tree

17.13 UN GHS Classification

17.14 NORMAN Suspect List Exchange Classification

17.15 EPA DSSTox Classification

17.16 PFAS and Fluorinated Organic Compounds in PubChem

17.17 MolGenie Organic Chemistry Ontology

18 Information Sources

  1. CAS Common Chemistry
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    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
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    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  4. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  5. European Chemicals Agency (ECHA)
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    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    1,3-Dihydro-1-(2-(4-(3-(trifluoromethyl)phenyl)-1-piperazinyl)ethyl)-2H-benzimidazol-2-on
    https://echa.europa.eu/substance-information/-/substanceinfo/100.170.970
    1,3-Dihydro-1-(2-(4-(3-(trifluoromethyl)phenyl)-1-piperazinyl)ethyl)-2H-benzimidazol-2-on (EC: 643-002-2)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/175879
  6. FDA Global Substance Registration System (GSRS)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  7. Hazardous Substances Data Bank (HSDB)
  8. ChEBI
  9. FDA Pharm Classes
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  10. LiverTox
  11. NCI Thesaurus (NCIt)
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    https://www.cancer.gov/policies/copyright-reuse
  12. Open Targets
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    https://platform-docs.opentargets.org/licence
  13. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  14. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  15. DailyMed
  16. Drug Gene Interaction database (DGIdb)
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    http://www.dgidb.org/downloads
  17. IUPHAR/BPS Guide to PHARMACOLOGY
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  18. Therapeutic Target Database (TTD)
  19. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency's (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
  20. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  21. EU Clinical Trials Register
  22. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  23. FDA Medication Guides
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  24. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  25. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  26. Japan Chemical Substance Dictionary (Nikkaji)
  27. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  28. Metabolomics Workbench
  29. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  30. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    flibanserin
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  31. PharmGKB
    LICENSE
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    https://www.pharmgkb.org/page/policies
  32. Pharos
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    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  33. SpectraBase
  34. Springer Nature
  35. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  36. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  37. Wikidata
  38. Wikipedia
  39. PubChem
  40. Medical Subject Headings (MeSH)
    LICENSE
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    https://www.nlm.nih.gov/copyright.html
  41. GHS Classification (UNECE)
  42. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  43. PATENTSCOPE (WIPO)
CONTENTS