Antidiarrheal
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
The animal data suggest low risk, but the human pregnancy experience is too limited to allow a more complete assessment of embryo/fetal risk. Nevertheless, an abstract suggests that the human risk also is low.
FETAL RISK SUMMARY
Loperamide is a synthetic opioid analog that is used for the treatment of diarrhea. It is available without a prescription. No published reports linking the use of loperamide with congenital defects have been located.
Reproduction studies with rats and rabbits at doses up to 30 times the human dose have revealed no evidence of impaired fertility, teratogenicity, or other fetal harm (1).
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 108 newborns had been exposed to loperamide during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Six (5.6%) major birth defects were observed (five expected), three of which were cardiovascular defects (one expected). No anomalies were observed in five other defect categories (oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias) for which specific data were available. The number of cardiovascular defects suggests a possible association, but other factors, including the mother’s disease, concurrent drug use, and chance, may be involved.
In a 1999 abstract, the pregnancy outcomes of 89 women exposed to loperamide in the 1st trimester were compared with matched controls (2). There were no significant differences between the groups in terms of major and minor malformations, spontaneous abortions, elective abortions, preterm delivery, and birth weights. However, in 21 mothers who took loperamide throughout gestation, birth weights tended to be lower (200 g) (ns) (2).
BREASTFEEDING SUMMARY
No reports describing the use of loperamide during lactation have been located. However, one study investigated loperamide oxide, a pharmacologically inactive prodrug that is reduced to loperamide as it progresses through the intestinal tract, during lactation (3). Six women in the immediate postpartum period, who were not nursing, were given two 4-mg oral doses of loperamide oxide 12 hours apart. Simultaneous plasma and milk samples were collected 12 hours after the first dose, and 6 and 24 hours after the second dose. Small amounts of loperamide oxide were measured in some of the plasma samples, but the mean loperamide oxide milk concentrations were <0.10 ng/mL (detection limit) at each sampling time. Mean loperamide milk concentrations for the three samples were 0.18, 0.27, and 0.19 ng/mL, respectively, corresponding to milk:plasma ratios of 0.50, 0.37, and 0.35, respectively (3). The American Academy of Pediatrics classifies loperamide as compatible with breastfeeding (4).
References
1.Product information. Imodium. McNeil Consumer, 2000.
2.Einarson A, Mastroiacovo P, Arnon J, Ornoy A, Addis A, Ritvanen A, Koren G. A prospective controlled multicentre study of loperamide in pregnancy (abstract). Teratology 1999;59:377.
3.Nikodem VC, Hofmeyr GJ. Secretion of the antidiarrhoeal agent loperamide oxide in breast milk. Eur J Clin Pharmacol 1992;42:695–6.
4.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776–89.