LOPERAMIDE

Fetal Risk Summary

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.

Breast Feeding Summary

Reports describing the passage of loperamide into breast milk after maternal ingestion of the drug have not 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 (2). 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 less than 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. Although these amounts are very small, an earlier source recommended that loperamide should not be used in the lactating mother because of the potential for adverse effects in the nursing infant (3). However, because of the absence of these effects, the American Academy of Pediatrics considers loperamide to be compatible with breast feeding (4).

References

1. Product information. Imodium. McNeil Consumer, 2000.
2. Nikodem VC, Hofmeyr GJ. Secretion of the antidiarrhoeal agent loperamide oxide in breast milk. Eur J Clin Pharmacol 1992;42:695–6.
3. Stewart JJ. Gastrointestinal drugs. In Wilson JT, ed. Drugs in Breast Milk. Balgowlah, Australia:ADIS Press, 1981:71.
4. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.