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Committee advises against approval of phenylephrine in acute hypotensive states
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The FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 8-2 to recommend against approval of IV phenylephrine to increase BP in acute hypotensive states, such as shock, with several panel members suggesting that wording in the indication may be too broad.
The question originally posed to the panel, however, included perioperative hypotension as an acute hypotensive state in the indication. Some members of the committee acknowledged the potential value of using phenylephrine (West-Ward Pharmaceuticals) in this capacity because the bulk of data presented demonstrated safety and efficacy when used during neuraxial anesthesia administration. Further, in clinical situations, phenylephrine is generally used as a short-term, intermittent bolus to treat the predicted hypotension that may occur with general or neuraxial anesthesia, according to a panel member.
“I voted no because ‘acute hypotensive state’ is a very broad term that includes various types of shock,” a committee member said. “However, I would also like to reiterate that it is useful for acute hypotension with anesthetics, so if we were to separate these two [indications], I could change my vote.”
Several committee members also took issue that the sponsor’s application was based on published studies only. Although some thought the existing data coupled with a long history of clinical experience with the drug were sufficient, others remained concerned about publication bias, the endpoints examined, and whether the analyses conducted were appropriate for the proposed indications. Additionally, some highlighted the need for further studies and different types of trials.
“I believe that to gain approval in the broader indication such as shock would require something along the lines of a noninferiority study against other agents,” said Scott Emerson, MD, PhD, professor of biostatistics at the University of Washington in Seattle.
Moreover, more safety data are required in different populations, according to committee chairman A. Michael Lincoff, MD.
“I agree that if an indication beyond those for neuraxial anesthesia is to be obtained, data on some end organ or at least safety, and ideally some degree of efficacy, depending on what comparator should be obtained pre-approval,” Lincoff, who is also director of the Cleveland Clinic Coordinating Center for Clinical Research, said.
Those in favor of approval, however, said the drug is already widely used.
“Although labeling may appear broad and we don’t have sufficient safety data to confirm, [phenylephrine] is in use in adult ICUs every day in this country,” said Joseph Tobin, MD, professor anesthesiology and pediatrics at Medical Center Boulevard in Winston-Salem, N.C. “I do believe clinicians understand the risk of unabated alpha agonism. … I feel comfortable with nearly 30 years of practicing with this drug.”
Although the FDA is not required to follow the recommendations of the advisory committee, it usually does.