Hypnotic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of fospropofol in human pregnancy have been located. The agent is converted to its active metabolite propofol for which there is limited human pregnancy experience but not in the first half of gestation. Although the animal data suggest low risk, human data are required for a complete assessment of the embryo–fetal risk. As with propofol, use of the prodrug near birth may cause transient depression of the newborn (see Propofol).
FETAL RISK SUMMARY
Fospropofol is a prodrug that is metabolized by alkaline phosphatases to propofol, which undergoes further metabolism. It is indicated for monitored anesthesia care sedation in adult patients undergoing diagnostic or therapeutic procedures. The mean elimination half-life of fospropofol is 0.88 hours, whereas the mean elimination half-life of propofol from fospropofol is 1.13 hours. Both fospropofol and its active metabolite propofol are highly plasma protein bound (about 98%) primarily to albumin (1).
Reproduction studies have been conducted in rats and rabbits. In these species, doses up to 0.6 and 1.7 times, respectively, the anticipated human dose for a 16-minute procedure based on BSA (HD) revealed no evidence of embryo–fetal harm or impaired fertility. In rats, the highest doses caused significant maternal toxicity, whereas in rabbits all doses caused significant maternal toxicity. When rats were given doses up to 0.2 times the HD from gestation day 7 through lactation day 20, no clear treatment-related effects on growth, development, behavior (passive avoidance and water maze), or fertility and mating capacity of the offspring were noted (1).
Long-term studies for carcinogenicity have not been conducted with fospropofol. The drug was not genotoxic in two assays, with or without metabolic activation. However, in a third assay, fospropofol was mutagenic in the presence of metabolic activation but the finding was thought to have been an artifact of the culture conditions (1).
It is not known if fospropofol crosses the human placenta. The molecular weight (about 332 for the disodium salt form) is low enough, but the extensive plasma protein binding and relatively short elimination half-life suggest that transfer will be limited. However, the active metabolite propofol does cross, with an umbilical vein:maternal vein ratio of 0.7 (see Propofol).
BREASTFEEDING SUMMARY
No reports describing the use of fospropofol during human lactation have been located. The molecular weight (about 332 for the disodium salt form) is low enough for excretion, but the extensive plasma protein binding and relatively short elimination half-life should limit the amount in milk. Small amounts of the active metabolite propofol are excreted into colostrum and milk following use of the agent for the induction and maintenance of maternal anesthesia during cesarean delivery (see Propofol).
Reference
1.Product information. Lusedra. Eisai, 2009.