Gina D Moore1, Alyssa M Walker, Robert MacLaren. 1. School of Pharmacy, University of Colorado Denver, 12631 E. 17th Ave., Mail Stop C238-L15, Aurora, CO 80045, USA. gina.moore@ucdenver.edu
Abstract
OBJECTIVE: To summarize the published clinical data on fospropofol, critically review the safety and efficacy information, and provide pertinent information for formulary review. DATA SOURCES: Data were collected from searches of MEDLINE (1966-June 30, 2009), EMBASE (1974-June 30, 2009), bibliographies of manuscripts, and www.fda.gov. Key search terms included fospropofol, Lusedra, Aquavan, sedative-hypnotic, and monitored anesthesia care. STUDY SELECTION AND DATA EXTRACTION: All Phase 1, Phase 2, and Phase 3 clinical trials studying the safety and efficacy of fospropofol were reviewed. DATA SYNTHESIS: Fospropofol is a water-soluble prodrug of propofol, a potent sedative-hypnotic agent. Propofol is highly lipophilic and is formulated in lipid-containing solvents, which have known disadvantages, including pain on injection, narrow therapeutic window with the potential to cause deep sedation, high lipid intake during long-term sedation, and risk of infection resulting from bacterial contamination. Due to its water solubility, fospropofol eliminates some of the known lipid emulsion-associated disadvantages of propofol and provides a more predictable peak onset of activity and more gradual recovery to a full state of consciousness. The pharmacokinetic and pharmacodynamic profiles of fospropofol make it an attractive agent for sedation for procedures of short duration. Unfortunately, the number of patients studied has been relatively small and the amount of safety data is limited. Of concern are reports of hypoxemia and hypotension; these reports are limited in number, but the episodes are serious and may require acute intervention. Although fospropofol holds promise for procedural sedation, due to limited safety data, the Food and Drug Administration has limited approval of fospropofol to monitored anesthesia care in patients undergoing diagnostic or therapeutic procedures. CONCLUSIONS: Fospropofol is a viable addition to the class of sedative-hypnotic agents due to the minimization of unwanted adverse effects of propofol and maintenance of a favorable pharmacokinetic profile facilitating sedation, anxiolysis, and rapid recovery. However, there are limited safety data to justify its use without the presence of dedicated anesthesia personnel.
OBJECTIVE: To summarize the published clinical data on fospropofol, critically review the safety and efficacy information, and provide pertinent information for formulary review. DATA SOURCES: Data were collected from searches of MEDLINE (1966-June 30, 2009), EMBASE (1974-June 30, 2009), bibliographies of manuscripts, and www.fda.gov. Key search terms included fospropofol, Lusedra, Aquavan, sedative-hypnotic, and monitored anesthesia care. STUDY SELECTION AND DATA EXTRACTION: All Phase 1, Phase 2, and Phase 3 clinical trials studying the safety and efficacy of fospropofol were reviewed. DATA SYNTHESIS: Fospropofol is a water-soluble prodrug of propofol, a potent sedative-hypnotic agent. Propofol is highly lipophilic and is formulated in lipid-containing solvents, which have known disadvantages, including pain on injection, narrow therapeutic window with the potential to cause deep sedation, high lipid intake during long-term sedation, and risk of infection resulting from bacterial contamination. Due to its water solubility, fospropofol eliminates some of the known lipid emulsion-associated disadvantages of propofol and provides a more predictable peak onset of activity and more gradual recovery to a full state of consciousness. The pharmacokinetic and pharmacodynamic profiles of fospropofol make it an attractive agent for sedation for procedures of short duration. Unfortunately, the number of patients studied has been relatively small and the amount of safety data is limited. Of concern are reports of hypoxemia and hypotension; these reports are limited in number, but the episodes are serious and may require acute intervention. Although fospropofol holds promise for procedural sedation, due to limited safety data, the Food and Drug Administration has limited approval of fospropofol to monitored anesthesia care in patients undergoing diagnostic or therapeutic procedures. CONCLUSIONS:Fospropofol is a viable addition to the class of sedative-hypnotic agents due to the minimization of unwanted adverse effects of propofol and maintenance of a favorable pharmacokinetic profile facilitating sedation, anxiolysis, and rapid recovery. However, there are limited safety data to justify its use without the presence of dedicated anesthesia personnel.