PMID- 28608926 OWN - NLM STAT- MEDLINE DCOM- 20180510 LR - 20180510 IS - 1365-2710 (Electronic) IS - 0269-4727 (Linking) VI - 42 IP - 5 DP - 2017 Oct TI - The pharmacodynamic effects of combined administration of flibanserin and alcohol. PG - 598-606 LID - 10.1111/jcpt.12563 [doi] AB - WHAT IS KNOWN AND OBJECTIVE: Flibanserin is a serotonin 5-HT(1A) agonist and 5-HT(2A) antagonist approved for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Because of the increased risk of hypotension- and syncope-related adverse events (AEs) observed with coadministration of flibanserin and alcohol, alcohol use is contraindicated. To provide a more comprehensive understanding of the interaction between flibanserin and alcohol, the results of a dedicated phase 1 alcohol-interaction study and a pooled analysis of phase 3 studies of premenopausal women with HSDD are presented. METHODS: In the phase 1 study, healthy participants (males [n=23] and females [n=2]) were randomly assigned to one of five sequence groups, which determined the order in which they were to receive flibanserin 100 mg or placebo, with or without ethanol 0.4 g/kg or 0.8 g/kg. Change from baseline in seated blood pressure, orthostatic vital signs, AEs and visual analogue scale sedation outcomes were examined. Blood samples were collected at baseline and for up to 4 hours after dosing to determine flibanserin area under the plasma concentration-time curve from 0 to 4 hours (AUC(0-4) ). Pooled data from five phase 3 studies of patients receiving flibanserin 100 mg once daily (n=1543), or placebo (n=1905), were analysed. RESULTS: In the phase 1 study, the incidence of hypotension and syncope increased when flibanserin was coadministered with ethanol. Sedation increased 20% and 27% from baseline with flibanserin plus ethanol 0.4 g/kg and 0.8 g/kg, respectively, at 4 hours post-dose. In the pooled analysis of phase 3 studies, 58.2% and 63.6% of participants receiving flibanserin or placebo, respectively, reported baseline alcohol use. In patients receiving flibanserin, fatigue and dizziness occurred more frequently in patients with vs. without alcohol use. WHAT IS NEW AND CONCLUSION: Results from this study suggest that increased incidence of hypotension- and syncope-related events may result from a pharmacodynamic interaction between flibanserin and alcohol, although the clinical significance of these interactions in real-world populations remains unclear. CI - (c) 2017 The Authors. The Journal of Clinical Pharmacy and Therapeutics Published by John Wiley & Sons Ltd. FAU - Stevens, D M AU - Stevens DM AD - Arbor Scientia, Carlsbad, CA, USA. FAU - Weems, J M AU - Weems JM AD - Trident University International, Cypress, CA, USA. FAU - Brown, L AU - Brown L AD - Valeant Pharmaceuticals North America LLC, Bridgewater, NJ, USA. FAU - Barbour, K A AU - Barbour KA AD - Valeant Pharmaceuticals North America LLC, Bridgewater, NJ, USA. FAU - Stahl, S M AU - Stahl SM AD - University of California San Diego School of Medicine, San Diego, CA, USA. LA - eng PT - Clinical Trial, Phase I PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial DEP - 20170613 PL - England TA - J Clin Pharm Ther JT - Journal of clinical pharmacy and therapeutics JID - 8704308 RN - 0 (Benzimidazoles) RN - 0 (Serotonin 5-HT1 Receptor Agonists) RN - 0 (Serotonin 5-HT2 Receptor Antagonists) RN - 37JK4STR6Z (flibanserin) SB - IM MH - Adult MH - Alcohol Drinking/*adverse effects MH - Area Under Curve MH - Benzimidazoles/*administration & dosage/adverse effects/pharmacokinetics MH - Double-Blind Method MH - Drug Interactions MH - Fatigue/chemically induced/epidemiology MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Premenopause MH - Serotonin 5-HT1 Receptor Agonists/administration & dosage/adverse effects/pharmacokinetics MH - Serotonin 5-HT2 Receptor Antagonists/administration & dosage/adverse effects/pharmacokinetics MH - Sexual Dysfunctions, Psychological/*drug therapy MH - Syncope/chemically induced/epidemiology MH - Young Adult OTO - NOTNLM OT - additive pharmacodynamic effects OT - central nervous system depression OT - ethanol OT - flibanserin OT - hypotension OT - syncope EDAT- 2017/06/14 06:00 MHDA- 2018/05/11 06:00 CRDT- 2017/06/14 06:00 PHST- 2017/01/05 00:00 [received] PHST- 2017/04/25 00:00 [accepted] PHST- 2017/06/14 06:00 [pubmed] PHST- 2018/05/11 06:00 [medline] PHST- 2017/06/14 06:00 [entrez] AID - 10.1111/jcpt.12563 [doi] PST - ppublish SO - J Clin Pharm Ther. 2017 Oct;42(5):598-606. doi: 10.1111/jcpt.12563. Epub 2017 Jun 13.