Loperamide is a synthetic piperidine derivative that acts via cholinergic, non-cholinergic, opiate and non-opiate receptor-mediated pathways. It is used as a smooth muscle relaxant for the symptomatic treatment of irritable bowel syndrome, acute and chronic diarrhoea, and in ileostomy patients.
The available evidence regarding the fetal effects of loperamide use in pregnancy is currently limited to three studies which collectively report the outcomes of more than 800 exposed infants. These studies report conflicting findings concerning the risk of malformation. One small study, which was only sufficiently powered to detect a major teratogenic effect, reported no increased risk of major malformations overall while a more sufficiently powered population-based study found an approximate 1.5 times increased risk in the occurrence of any severe malformation. The later study also described an increased risk of hypospadias specifically, but refuted an earlier finding of a possible association between maternal loperamide use in early pregnancy and an increased risk of cardiac defects. Due to possible data confounding from the underlying maternal condition and concomitant medication exposure, it is not currently possible to conclude that maternal loperamide use in early pregnancy increases the risk of severe malformation or hypospadias specifically. Further studies are required to confirm or refute these findings.
No evidence of an increased risk of miscarriage, low birth weight, preterm delivery or neonatal complications has been provided by these studies. No studies investigating intrauterine death/stillbirth, neurodevelopmental impairment or childhood cancer risks have been located in the literature. However, the limited and conflicting nature of these data, and confounding factors present in the studies, mean that it is difficult to draw definitive conclusions regarding the safety of use of loperamide during pregnancy.
Use of loperamide in pregnancy should, where possible, involve discussion with the patient about the limited nature of the data and should be avoided unless the clinical benefits outweigh the as yet undetermined risks. Exposure to loperamide at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.