Gastrointestinal Agent (Antidiarrheal)
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of crofelemer in human pregnancy have been located. Doses used in animal reproduction studies were compared with the human dose based on body weight and, in one species, maternal toxicity occurred, so the results are not interpretable. Nevertheless, the botanical drug is minimally absorbed, so clinically significant exposure of the embryo–fetus probably does not occur.
FETAL RISK SUMMARY
Crofelemer, a botanical drug substance, is an oral inhibitor of two functions of intestinal epithelial cells that regulate fluid secretion, thus preventing high-volume water loss in diarrhea. It is indicated for symptomatic relief of noninfectious diarrhea in patients with HIV/AIDS on anti-retroviral therapy. The drug is minimally absorbed and concentrations of crofelemer in plasma are below the level of quantitation (50 ng/mL). No metabolites have been identified (1).
Reproduction studies have been conducted in rats and rabbits. In rats, oral doses up to 177 times the recommended daily human dose of 4.2 mg/kg (RHD) revealed no evidence of fetal harm. There also was no evidence of adverse prenatal or postnatal effects in offspring. In rabbits, a dose that was about 96 times the RHD caused abortions and resorptions of fetuses, but maternal toxicity also was evident.
Long-term studies of carcinogenicity have not been conducted, but three assays for mutagenicity were negative. At doses up to 177 times the RHD, crofelemer had no effects on fertility or reproductive performance of male and female rats (1).
It is not known if crofelemer crosses the human placenta. Although high, the molecular weight of the botanical drug cannot be determined because of extensive polymerization. Moreover, systemic concentrations of the drug are minimal, so exposure of an embryo or fetus probably appears to be nil.
BREASTFEEDING SUMMARY
No reports describing the use of crofelemer during human lactation have been located. Because the drug is minimally absorbed, clinically significant amounts of crofelemer in milk probably do not occur.
Reference
1.Product information. Fulyzaq. Salix Pharmaceuticals, 2013.