New Drug Introduction: AddyiTM/ flibanserin
Pharmacology
Manufacturer
Approval Date
Indications
Contraindications
Black Box Warnings
Warnings/
Precautions
Pregnancy/Lactation
Pharmacokinetics
Drug Interactions –
Object Drugs
Drug Interactions –
Precipitant drugs
Adverse Effects
Monitoring Efficacy
Monitoring Toxicity
Dosing –Initial/Usual
Dosing - Max
Renal Adjustment
Hepatic Adjustment
 Agonist of 5-HT1A
 Antagonist of 5-HT2A, 5-HT2B, 5-HT2C, and dopamine D4 receptor
 Exact mechanism of action is unknown
Sprout Pharmaceuticals Inc.
August 18, 2015
Treatment of hypoactive sexual desire disorder (HSDD) in
premenopausal women
Alcohol intake, hepatic impairment, and concomitant use with
moderate or strong CYP3A4 inhibitors
Hypotension and syncope in specific situations:
 Contraindicated with alcohol
 Contraindicated with strong or moderate CYP3A4 inhibitors
 Contraindicated in patients with hepatic impairment
**REMS Program due to the above
 Hypotension and syncope with flibanserin alone
 CNS depression (i.e. somnolence and sedation)
Category: unknown
Lactation Recommendation: not recommended
A – F: 33%, Tmax: 0.8 hours, steady state: reached after 3 days
D – 98% protein binding
M – Primarily CYP3A4 metabolism (lesser extent CYP2C19) into two
inactive metabolites
E – T1/2: 11 hours
Digoxin (↑2-fold), PGP substrates, simvastatin (↑1.3-fold), oral
contraceptives (↑~1.1-fold), and buproprion (hydroxybupropion ↓9%)
fluconazole (↑7-fold), ketoconazole (↑4.5-fold), itraconazole (↑2.6fold), grape fruit juice (↑1.4-fold), oral contraceptives (↑1.4-fold), and
paroxetine (↓4%), rifampin (↓95%) and etravirine (↓21%)
Dizziness (11.4%) [2.2%]
CNS depression (21%) [8%]
Syncope (0.4%) [0.2%]
Somnolence (11.2%) [2.9%]
Hypotension (0.2%) [<0.1%]
Insomnia (4.9%) [2.8%]
Fatigue (9.2%) [5.5%]
Dry mouth (2.4%) [1.0%]
Nausea (10.4%) [3.9%]
Increase in sexual desire
Monitor for side effects listed above
100mg PO once daily at bedtime
200mg PO once daily at bedtime
50mg PO once daily at bedtime (↑1.1-fold in mild/moderate, ↑1.2-fold
in severe)
Contraindicated
Cost: Source: Forbes accessed 08/18/2015
Drug Name
Dose
TM
Addyi - flibanserin
100mg
$ (30 days)
$400
Summary
 AddyiTM, flibanserin, is first-in-class for the treatment of hypoactive sexual desire
disorder (HSDD) in premenopausal women
 Dosing is 100mg PO daily at bedtime, 50mg for any level of renal impairment
 Most common adverse drug events include; dizziness (as well as hypotension,
syncope), CNS depression, nausea and sleep disturbances.
 Black box warning (BBW) for hypotension and syncope related to alcohol intake, coadministration with moderate to strong CYP3A4 inhibitors, and use in patients with
hepatic impairment
 Flibanserin has a required REMS program
References:
1. AddyiTM package insert. Sprout Pharmaceuticals Inc. August 2015.
2. LaMattina, J. Forbes Website. “You can call it the ‘female viagra,’ but the libido pill,
Addyi, won’t come close to Viagra’s Impact.”
http://www.forbes.com/sites/johnlamattina/2015/08/18/you-can-call-it-the-femaleviagra-but-the-libido-pill-addyi-wont-come-close-to-viagras-impact. Accessed
September, 1st 2015.
3. Sprout Pharmaceuticals Inc. AddyiTM approval announcement.
http://www.sproutpharma.com/sprout-pharmaceuticals-receives-fda-approval-addyiflibanserin-100-mg/. Accessed September, 7th 2015.
Date Prepared: 09/24/2015
Editor: Peter G. Koval, Pharm.D., BCPS
Author: Tommi Cooke, Pharm.D. Candidate, UNC Eshelman School of Pharmacy