Consumer Health Info, Health Info
Publication Date: July 30, 2019
By: Rachel Grimsley, (RN, BSN, MSN) Volunteer Health Officer
According to Sprout Pharmaceuticals, the drug company that makes Addyi, the drug is believed to work on the part of the brain involved in sexual interest and desire. It belongs to a class of drugs that has sedative properties, known as serotonin 1A receptor agonists and a serotonin 2A receptor antagonists. However, the exact mechanism of action is not fully understood.
The FDA approved Addyi in 2015 and revised its approval in 2019 to include a black box warning to avoid taking Addyi with alcohol.
A new randomized trial was conducted that attempted to address both concerns. The company changed the definition of effectiveness and instructed women to take the pill at night. Using the new definition of effectiveness, the trial found that the pill increased desire in about 10% of the women who used it. In those women, increased desire resulted in about one more sexually satisfying event per month. Even with nighttime dosing, however, the new trial found that women who took Addyi were twice as likely to be involved in car accidents and other accidental injuries as those who took the placebo.
After reviewing these results, the FDA asked the sponsor to investigate whether the serious adverse events resulted from Addyi being used in conjunction with other medications. Some of the less dangerous side effects, including sleepiness, dizziness, and fatigue, were reported more often in women who used hormonal contraceptives. This is because hormonal contraceptives are known to affect a certain enzyme (CYP3A4), which can increase flibanserin exposure by 40%.
Beyond hormonal contraceptives, various other medications described in the FDA medication guide could worsen adverse events such as fainting or low blood pressure when taken concurrently with Addyi. During Phase III trials, women who were already taking certain drugs, such as antiepileptic drugs, anti-anxiety drugs (benzodiazepines), antidepressants, antipsychotics, mood stabilizers, narcotics, certain vaginal lubricants, or even the herb St. John’s wort, were barred from participating.
The FDA also asked the sponsor to study the interaction between Addyi and alcohol. The clinical trials raised the possibility that accidents caused by Addyi were more common in women who drank alcohol. The study found that taking Addyi while drinking alcohol caused dangerously low blood pressure and sudden loss of consciousness. As a result, the FDA added a warning that women should not drink alcohol while taking Addyi.
Gaps in the effectiveness studies were equally troubling. The drugmaker required that women be heterosexual and in a stable relationship, excluding lesbians and other women who are sexually active outside committed relationships. Of the 3,099 women in these trials, 89%, were identified as White. The FDA was not able to determine whether Addyi affects women of color differently. The participants who enrolled in Addyi’s initial clinical trials were generally very healthy women, in part due to the long list of exclusion criteria for the trials. Given that the drug was tested in a narrowly restricted group of women, the extent to which the results of these trials can be generalized to the public is unknown and further studies are needed.
When the FDA approved Addyi in 2015, it mandated that the pharmaceutical company conduct three follow up studies. Each of these follow-up studies was intended to gauge better the effects of alcohol on women taking Addyi. The final results from these studies were submitted to the FDA in July and August of 2018.
The studies explored the effects of varying amounts of alcohol taken in the morning with Addyi, the impact of taking Addyi after two drinks with dinner, and how women are affected when they drink alcohol at different times before taking a dose of Addyi.
The FDA required the updated label to say women should discontinue drinking alcohol at least two hours before taking Addyi at bedtime or else skip their evening dose, and women should also refrain from consuming alcohol until the following morning.
The NWHN believes Sprout Pharmaceuticals must ensure this new labeling information is visible and prominent in every place Addyi is prescribed, including third-party telemedicine websites.
Addyi is intended to help premenopausal women with HSDD. If you have HSDD and want to see if Addyi can help you, we encourage you to follow the FDA’s advice and not drink alcohol at least two hours beforehand and eight to ten hours afterward.
Updated 11/30/2023 by Rachel Grimsley, RN, BSN, MSN, Nurse Writer
