Stevens D M, Weems J M, Brown L, Barbour K A, Stahl S M
Arbor Scientia, Carlsbad, CA, USA.
Trident University International, Cypress, CA, USA.
J Clin Pharm Ther. 2017 Oct;42(5):598-606. doi: 10.1111/jcpt.12563. Epub 2017 Jun 13.
Flibanserin is a serotonin 5-HT agonist and 5-HT 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.
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 ). Pooled data from five phase 3 studies of patients receiving flibanserin 100 mg once daily (n=1543), or placebo (n=1905), were analysed.
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.
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.
氟班色林是一种5-羟色胺（5-HT）激动剂和拮抗剂，已被批准用于治疗绝经前女性获得性广泛性性欲减退障碍（HSDD）。由于同时服用氟班色林和酒精会增加低血压和晕厥相关不良事件（AE）的风险，因此禁止饮酒。为了更全面地了解氟班色林与酒精之间的相互作用，本文呈现了一项专门的1期酒精相互作用研究结果以及对绝经前HSDD女性3期研究的汇总分析。
在1期研究中，健康参与者（男性[n = 23]和女性[n = 2]）被随机分配到五个序列组之一，这决定了他们接受100 mg氟班色林或安慰剂的顺序，同时服用或不服用0.4 g/kg或0.8 g/kg乙醇。检查坐位血压、直立位生命体征、不良事件和视觉模拟量表镇静结果相对于基线的变化。在基线以及给药后长达4小时采集血样，以确定0至4小时血浆浓度-时间曲线下氟班色林的面积（AUC）。对五项接受每日一次100 mg氟班色林（n = 1543）或安慰剂（n = 1905）的患者3期研究的汇总数据进行了分析。
在1期研究中，氟班色林与乙醇同时服用时，低血压和晕厥的发生率增加。给药后4小时，氟班色林加0.4 g/kg和0.8 g/kg乙醇时，镇静作用分别比基线增加了20%和27%。在3期研究的汇总分析中，分别有58.2%和63.6%接受氟班色林或安慰剂的参与者报告有基线饮酒情况。在接受氟班色林的患者中，饮酒者比不饮酒者疲劳和头晕的发生率更高。
本研究结果表明，氟班色林与酒精之间的药效学相互作用可能导致低血压和晕厥相关事件的发生率增加，尽管这些相互作用在实际人群中的临床意义仍不明确。
