A new study in The Journal of Sexual Medicine confirms last year’s revised labeling of the FDA-approved flibanserin (Addyi, Sprout Pharmaceuticals) for treating hypoactive sexual desire disorder (HSDD) in premenopausal women. The revised labeling states that consumption of moderate amounts of alcohol does not have an additive effect on the adverse events (AE) profile of flibanserin 100 mg in healthy premenopausal women, when the product is taken at bedtime and alcohol is consumed 2 or more hours beforehand.
“Since 2015, when the product was FDA approved, I believed that the labeling was misleading, erroneous and scary to patients, because from the early days of development, this medicine was meant to be given at bedtime,” said the study’s senior author, James A. Simon, MD, a clinical professor of ob/gyn at George Washington University in Washington, D.C.
Dr. Simon told Contemporary OB/GYN that the alcohol interaction study that prompted the adverse labeling was a single clinical research trial with a design mandated by the FDA, whereby the test medication was given with alcohol first thing in the morning. “But the medicine was never intended to be given at that time,” he said. “Therefore, flibanserin had a predestined adverse profile only made worse with simultaneously administered alcohol.”
The current single-center, randomized, double-blind, single-dose crossover study included 96 premenopausal women (mean age 31) who were randomly assigned to flibanserin 100 mg or placebo with ethanol 0.2 g/kg, 0.4 g/kg or 0.6 g/kg, or flibanserin 100 mg only or matching placebo. Treatments were administered using a worst-case approach, including morning dosing and consumption of alcohol within 10 minutes.
Incidence of dizziness for flibanserin + ethanol was 39.8% for ethanol 0.6 g/kg, 34.1% for 0.4 g/kg and 27.4% for 0.2 g/kg, compared to 31.1% for flibanserin without ethanol. Vital signs data also showed no effect of ethanol concentration on orthostatic blood pressure, vertigo or hypotension, and no cases of syncope were observed.
Coadministration of 0.6 g/kg ethanol (equivalent of three 1.5-oz shots of 80-proof spirits in a 70-kg person [~154 lb) with flibanserin was associated with an increased incidence of dizziness that was not statistically significant; however, after administration of flibanserin with 0.4 g/kg or 0.2 g/kg ethanol, the incidence of dizziness was comparable with that seen with flibanserin alone.
However, a significantly greater percentage of women given flibanserin with 0.6 g/kg or 0.4 g/kg of alcohol were deemed “Participants in Whom Standing Blood Pressure Was Not Obtained” versus women given flibanserin alone. Still, the overall incidence of AEs was comparable for flibanserin alone or with ethanol: 96.7% and 90.5% to 97.6%, respectively.
The percentage of participants in whom standing blood pressure measurements were not obtained at ≥ 1 timepoint was significantly higher for participants administered flibanserin with 0.6 g/kg and 0.4 g/kg of alcohol compared with flibanserin alone, showing an apparent alcohol dose response.
None of the study results surprise Dr. Simon. “We know that alcohol is a central nervous system (CNS) depressant, so it was perfectly reasonable to expect that a CNS depressant known to cause drowsiness would make women tired, sleepy or in this case dizzy, if the medicine was taken with alcohol in the morning,” he said.
The study is one of four recent studies that support concomitant use of flibanserin and alcohol. “Not only did these studies lead to changing the label to represent the truth, but to advise patients the safest way to take the medicine when involved with social drinking, which is pretty much a part of our culture,” Dr. Simon said.
Flibanserin is extremely safe when following the guidelines of the new label, according to Dr. Simon, medical director of IntimMedicine Specialists, a Washington, D.C., practice that provides sexual medical services to men and women. “Previously, the patient had to sign an affidavit, guaranteeing the practitioner who wrote the prescription that the patient would not drink any alcohol,” he said.
Based on the new labeling, Dr. Simon anticipates an increase in flibanserin prescribing. “Many women drink as part of their social activities, which up until recently severely limited the perceived safety of flibanserin and the willingness of women to take the product,” he said.
Dr. Simon is a consultant to Sprout Pharmaceuticals Inc.