Fospropofol disodium injection, an intravenous sedative-hypnotic agent for sedation in adults undergoing diagnostic or therapeutic procedures, is one step from an FDA OK after the agency’s Advisory Committee on Anesthetic and Life Support Drugs voted 6 to 3 (with one abstention) in favor of approval last month. Among the draft discussion points the advisory committee focused on were how practitioners can reasonably determine depth of sedation to determine supplemental dosing, and whether fospropofol disodium injection can be safely managed by providers without training in general anesthesia.
“The drug was essentially designed to try to displace propofol ? and the financial ramifications of paying an anesthesiologist to administer it,” says Dr. Plavin, who testified at the Advisory Committee on Anesthetic and Life Support Drugs hearing on the anesthetic. Fospropofol disodium injection is a proprietary water-soluble prodrug of propofol that, after intravenous injection, is converted by an enzymein the body into propofol. “You’re essentially dealing with active form of propofol, which means it doesn’t have a reversal agent. There’s a very narrow band range of safe dosing, and the practitioner administering fospropofol for sedation/anesthesia should have the education and training to identify and manage the airway and cardiovascular changes that occur in a patient who enters a state of general anesthesia, as well as the ability to assist in the management of complications.?
The agency did recommend, in a 9-1 vote, that the drug be used only by appropriately trained healthcare providers and that further studies be conducted in specific patient populations, including those with a variety of comorbidities, those weighing less than 60 kg and the elderly. Data from one Phase II and one Phase III trial in patients undergoing colonoscopy, a Phase III trial in patients undergoing bronchoscopy, and an open-label study in patients undergoing a variety of minor surgical procedures form the foundation of the fospropofol disodium injection New Drug Application. In total, data from 21 clinical studies involving 1,611 individuals are included in the application. The clinical trials were conducted by non-anesthesia healthcare professionals, and study drugs were administered by medical personnel as dictated by local investigative site guidelines.
Eisai Corporation of North America and its U.S. subsidiary, MGI Pharma, said in a statement after the hearing that it was “encouraged ALSDAC’s support of the efficacy and safety results of fospropofol disodium,” and that it believes “the clinical trial data support the use of this product by anesthesiologists and nonanesthesia healthcare professionals.”
“When you think about it, that’s really a limited number of patients, and data on only 300 to 350 were presented at the hearing,” says Dr. Plavin, who is also the vice-chair and a founding board member of the National Coalition for Quality Colorectal Cancer Screening and Care. “And even there, they came up a little short on the patient safety profile: There were problems with hypoxemia, blood pressure changes, inability to arouse, and other symptoms commensurate with general anesthesia. They were looking for, but didn’t find, dose responses where the drug is effective but doesn’t have the side effects of propofol.
“This agent should be administered only by persons trained in the administration of general anesthesia and not involved in the conduct of the surgical/diagnostic procedure. It’s not worth taking chances and hoping for the best.”
FDA reviewers are scheduled to make a decision about final approval on July 26; they are not bound by the advisory committee’s recommendations, but generally follow its advice.
