(flibanserin)

South University School of Pharmacy

Savannah, Georgia

Tekerra Branch, Eric Bracewell, Sarah Ehorn, Yousrah Elsirafy, Cole Fragapane, Kevin Kelly,
Kayla Scheps, Shane Spacek, Annie Woodard

INTRODUCTION
Flibanserin was originally developed by Boehringer Ingelheim as an
antidepressant, but both phase 3 clinical trials failed to
demonstrate efficacy against a placebo. The rights to the drug were
then acquired by Sprout Pharmaceuticals with the intention of
developing this drug for the treatment of hypoactive sexual desire
disorder (HSDD). Flibanserin was then approved for this indication
in premenopausal women in June 2015 with some special
provisions.

OBJECTIVES

DRUG INTERACTIONS

Alcohol increases increase the risk of hypotension, syncope,

and CNS depression.
CNS depressants increase the risk of CNS depression.

MECHANISM OF
ACTION

The exact mechanism in the treatment of hypoactive sexual desire disorder in

premenopausal women is not known.
Flibanserin exhibits agonist activity at 5-HT1A and antagonist activity at 5-HT2A;
moderate antagonist activity is seen at the 5-HT2B, 5-HT2C, and dopamine D4
receptors.

CYP3A4 enzyme inhibitors increase the effects of flibanserin,

and increase the risk of hypotension and syncope.
Drowsiness; 11%

CYP2C19 enzyme inhibitors increases the effects of flibanserin,

and increase the risk of hypotension, syncope, and CNS
depression.
CYP3A4 enzyme inducers weaken the effects of flibanserin.
Digoxin and other P-glycoprotein substrates increases digoxin
concentrations, which may lead to digoxin toxicity.

DOSING
No Adverse
Reaction; 53%

Post-Synaptic
5-HT2A agonist

WARNINGS &
PRECAUTIONS

Inhibited
5-HT
Neurons

SEROTONIN
DOPAMINE
NOREPINEPHRINE

INDICATIONS/
CONTRAINDICATIONS

Used for treatment in:

Premenopausal women
Low sexual desires, known as hypoactive sexual desire disorder (HSDD).
Associated with distress and interpersonal difficulties

The drug directly influences neurotransmitter receptors

of both serotonin and dopamine.

CLINICAL EFFICACY &

SAFETY EVALUATION

Avoid grapefruit juice

Three phase 3 trials showed the following results, as summarized by the FDA:

Should be avoided in women who are pregnant

From a median baseline of about 2-3 satisfying sexual experiences per month, flibanserin resulted in a median
placebo-corrected increase of about 0.5-1.0 SSEs per month.

Because of potential that it may be excreted, 

breast-feeding is not recommended

From a mean baseline of about 1.8-1.9 on the FSFI desire score, flibanserin resulted in a placebo-corrected mean increase
of 0.3-0.4 (the FSFI desire score range is 1.2-6.0).

PHARMACOKINETICS

From a mean baseline of 3.2-3.4 on the distress score, flibanserin resulted in a placebo corrected mean improvement of
0.3-0.4 (on a scale of 0-4)

Figure 1.2

Psychotropic drug with dual action

Agonist of Serotonin G protein coupled receptor 5-HT1A decreased cAMP and potassium channel opening
Antagonist against Serotonin G protein coupled receptor 5-HT2A
prevent closing of potassium channels
Moderate antagonist against Serotonin receptors 5-HT2B, 5-HT2C,
and Dopamine D4 Receptors

CYP3A4 Inhibitors
Using this drug with moderate or strong CYP3A4 inhibitors increase the
concentration of Addyi.

Metabolism via hepatic CYP3A4 and CYP2C19 oxidation

98% Plasma protein binding, mainly Albumin

33% Oral Bioavailability

11 hrs Half-life, varies depending on hepatic functionality; 0.75-4

hrs for Peak
51% Fecal and 44% Urinary Excretion
Steady state reached after 3 days of dosing

DISCUSSION
Flibanserin is the first drug of its kind to increase sexual
desire in premenopausal women.

Hypotension and syncope have occurred while

taking this medication

Contraindications
Alcohol Consumption
Before the patient takes part of this restricted program, the doctor will assess
the patients probability of not consuming alcohol. They should also assess
the patients social habits and look at past history with alcohol.

Hepatic Impairment
Hepatic impairment will increase the concentration of the drug and cause
Hypotension and fainting.

After 8 weeks, if symptoms have not

improved, flibanserin should be
discontinued

Figure 1.1 - Adverse reactions reported during

clinical trial evaluation of flibanserin.

Avoid alcohol while taking Addyi

3
SSE (Stanardized)
Mean change from Baseline (SE)

Disinhibited
NE
Neurons

Orally: one tablet (100 mg) taken at

bedtime for HSDD

Nausea; 10%

No pregnancy category established

Disinhibited
DA
Neurons

For use in females only

Fatigue; 9%

Insomina; 5%

PREGNANCY PRECAUTIONS

Post-Synaptic
5-HT1A agonist

METHODS

Oral tablet; 100mg

Dizzness; 12%

Provide an overview on the pharmacology of Flibanserin

Review the clinical efficacy and safety guidelines in Flibanserin

AVAILABILITY

ADVERSE EFFECTS

SSEs (Satisfying Sexual Events) Mean Change from Baseline in

three Phase 3 Trials

Placebo

Addyi contains the following US Boxed Warning

Contraindicated with alcohol
Contraindicated with CYP3A4 inhibitors
Contraindicated in patients with hepatic impairment

Flibanserin 100mg qhs

Addyi is under the Risk Evaluation and Mitigation Strategy
(REMS) called Addyi REMS program.

2.5

Requirements of the ADDYI REMS Program include:

Prescribers must be certified with the program by enrolling

and completing training.

1.5

Pharmacies must be certified with the program and must only

dispense to patients pursuant to a prescription from a
certified prescriber.

- Prescribers should factor in behaviors and lifestyle before

prescribing flibanserin.

0.5
0

Study 147

Study 71

Study 75

Downregulation of serotonin pathways coupled with

upregulation of dopamine pathways result in improved
femal sexual libido.
Further research is needed regarding the exact
mechanism of action as well as the risks of
administration during lactation.

REFERENCES

1. Joffe HV, Chang C, Sewell C, et al. FDA Approval of Flibanserin Treating Hypoactive Sexual Desire
Disorder. New England Journal of Medicine. 2016; 374:101-104
2. Sathyanarayana Rao T, Andrade C. Flibanserin: Approval of a controversial drug for a controversial disorder.
Indian Journal of Psychiatry. 2015;57(3). http://search.proquest.com/docview/1724572796?accountid=87314.
doi: http://dx.doi.org/10.4103/0019-5545.166630.

3. Frazer A, Hensler JG. Serotonin Receptors. In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic
Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999.
Available from: http://www.ncbi.nlm.nih.gov.southuniversity.libproxy.edmc.edu/books/NBK282 34/
4. Product update. Journal of Psychosocial Nursing & Mental Health Services. 2015;53(11):18-n/a.
http://search.proquest.com/docview/1765317023?accountid=87314. doi:
http://dx.doi.org/10.3928/02793695-20151021-44
5. Gellad, W. F., Flynn, K. E., & Alexander, G. C. (2015). Evaluation of flibanserin: science and advocacy at the
FDA. Jama, 314(9), 869-870.
6. FDA Prescribing, Side effects and Uses Avaialable at http://www.drugs.com/pro/addyi.html August 8 2015.
Accessed on July 24, 2016. Flibanserin. In: Clinical Pharmacology. Tampa (FL): Gold Standard. [updated
08/24/15; accessed 07/17/16].
http://www.clinicalpharmacology-ip.com.southuniversity.libproxy.edmc.edu/Forms/drugoptions.aspx?cpnu
m=4706&n=Addyi&t=0&enh=1 .