The Food and Drug Administration has denied Sprout Pharmaceutical’s request to remove the Boxed Warning and contraindication regarding the use of Addyi (flibanserin) with alcohol. The agency noted in a safety labeling change order, that a review of postmarketing data submitted by the company did not adequately address the safety issues to make such a change.

When Addyi was first approved in 2015 for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women, the FDA required Sprout to conduct additional studies on its interaction with alcohol. In February 2018, the agency mandated safety-related labeling changes after new information emerged regarding alcohol-related adverse effects from postmarketing trials.

In March 2018, Sprout submitted a proposal to the FDA to remove the Boxed Warning and alcohol contraindication in the labeling based on data from a postmarketing study. However, the agency found that the findings supported the need for inclusion of this safety information; missing or delayed blood pressure measurements in the trial led the FDA to question whether the risk of hypotension and syncope were properly assessed. In July 2018, the company again submitted their rationale for removing the Boxed Warning and the alcohol contraindication stating that the risks did not meet the regulatory definition of a serious adverse reaction.

The FDA, however, stated that based on a “careful review of available data […] removing this important safety information was not acceptable for the protection of public health.” The FDA’s final assessment found “the risk of severe hypotension/syncope when (1) Addyi and alcohol are taken at the same time, (2) Addyi is taken with moderate to strong CYP3A4 inhibitors, or (3) Addyi is used in patients with hepatic impairment to be so serious in proportion to the potential drug benefit.” Additional postmarketing studies did however show that the risk of severe hypotension and syncope was reduced when women who consumed up to 2 alcoholic drinks waited at least 2 hours before taking the drug.

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Outlined in the labeling order, the agency is requiring updates to the Boxed Warning, Contraindication, Warnings and Precautions, and Adverse Reactions sections of the labeling to clarify that women should discontinue drinking at least 2 hours before taking Addyi at bedtime and should not consume alcohol at least until the morning after taking a bedtime dose. In addition, the FDA is requiring that details of the Addyi-alcohol interaction studies be included in the labeling to assist prescribers. Moreover, a Risk Evaluation and Mitigation Strategy (REMS) continues to be necessary to ensure that the benefit of Addyi outweighs the risks of hypotension/syncope with Addyi-alcohol interaction.

“We work diligently with companies to make labeling updates but occasionally are unable to reach agreement,” said Julie Beitz, MD Director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research’s Office of New Drugs. “In those rare cases, such as with Addyi today, we have important authorities to compel companies to make safety labeling changes that are critical for the safe use of an approved product.”

For more information visit FDA.gov.