Antidiarrheal/Antiemetic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of alosetron in human pregnancy have been located. Because the drug is restricted by the manufacturer to severe diarrhea-predominant irritable bowel syndrome, pregnancy exposures are probably infrequent. The animal data suggest low risk, but the absence of human pregnancy experience prevents an assessment of the embryo–fetal risk. Limited information for other agents in this class (e.g., see Ondansetron) does not suggest a risk of teratogenicity. Therefore, if indicated, alosetron should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Alosetron is a selective antagonist of the serotonin 5-HT3 receptor type. It is the same pharmacologic class as dolasetron, granisetron, ondansetron, and palonosetron. Although classified as an antiemetic, alosetron is indicated for the treatment of irritable bowel syndrome in women whose primary symptom is severe chronic diarrhea. Alosetron is extensively metabolized to metabolites with unknown biologic activity. About 82% is bound to plasma proteins and the terminal elimination half-life is very short (about 1.5 hours) (1).
Reproduction studies have been conducted in rats and rabbits. In rats, doses up to about 160 times the recommended human dose based on BSA (RHD) revealed no evidence of impaired fertility or fetal harm. Similar findings were observed in rabbits given doses up to about 240 times the RHD. In addition, dose up to about 160 times the RHD had no effect on reproductive performance in male or female rats (1).
It is not known if alosetron crosses the human placenta. The molecular weight of the free base (about 295) and moderate plasma protein binding suggest that the drug will cross to the embryo–fetus, but the very short terminal elimination half-life will limit the amount of drug at the maternal:fetal interface.
BREASTFEEDING SUMMARY
No reports describing the use of alosetron during human lactation have been located. The molecular weight of the free base (about 295) and moderate plasma protein binding suggest that the drug will be excreted into breast milk. However, the very short terminal elimination half-life (about 1.5 hours) suggests that the amount of drug in milk will be minimal. The effects of this exposure on a nursing infant are unknown. However, because of the potential for severe toxicity (e.g., gastrointestinal symptoms that have caused deaths in adults), alosetron should probably not be used in women who are breastfeeding.
Reference
1.Product information. Lotronex. GlaxoSmithKline, 2004.