Parasympatholytic
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: Limited Human Data—Potential Toxicity
PREGNANCY SUMMARY
The use of dicyclomine during human pregnancy does not appear to represent a risk to the fetus or newborn. A 1990 review on the teratogenic risk of commonly used drugs categorized the risk from dicyclomine as “none” (1).
FETAL RISK SUMMARY
This anticholinergic/antispasmodic agent was a component of a proprietary mixture (Bendectin, others) used for the treatment and prevention of pregnancy-induced nausea and vomiting from 1956 until 1976, when the product was reformulated. Dicyclomine was removed at that time because it was discovered that it did not contribute to the effectiveness of the mixture as an antiemetic (see also Doxylamine).
Animal studies conducted with dicyclomine alone, and in combination with doxylamine and pyridoxine (i.e., Bendectin), have found no evidence of impaired fertility or adverse fetal effects (2,3).
In the Collaborative Perinatal Project, 1024 mother–child pairs of the 50,282 studied were exposed to dicyclomine during the 1st trimester (4, pp. 346–356). It was the most common parasympatholytic agent consumed by the women studied. A statistically significant association (standardized relative risk (SRR) 1.46) was discovered for minor malformations with 21 malformed children (4, p. 353). Other defects with an SRR greater than 1.5, and the number of affected newborns, were polydactyly in blacks (SRR 1.89; N = 6; 277 black mothers), macrocephaly (SRR 8.8; N = 3), diaphragmatic hernia (SRR 12.0; N = 3), and clubfoot (SRR 1.8; N = 7) (3, pp. 353, 477). For use anytime during pregnancy, 1593 women consumed dicyclomine and an increased SRR was measured for macrocephaly (6.2; N = 3) and pectus excavatum (1.8; N = 9) (4, p. 492). The authors of this study, however, strongly cautioned that a causal relationship could not be inferred from any of these data, especially when the drug was used after the 1st trimester, and that independent confirmation was required with other studies.
A retrospective study published in 1971, involving more than 1200 mothers, examined the relationship between drugs and congenital malformations (5). This investigation found that significantly fewer mothers of infants with major anomalies, as compared with normal controls, took antiemetics during the first 56 days of pregnancy. Dicyclomine was the fourth most frequently ingested antiemetic.
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 642 newborns had been exposed to dicyclomine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 31 (4.8%) major birth defects were observed (27 expected). Specific data were available for six defect categories, including (observed/expected) 5/6 cardiovascular defects, 1/1 oral clefts, 0/0.5 spina bifida, 0/1 limb reduction defects, 0/2 hypospadias, and 3/1 polydactyly. Only with the latter defect is there a suggestion of a possible association, but other factors, including the mother’s disease, concurrent drug use, and chance may be involved.
BREASTFEEDING SUMMARY
No published reports on the excretion of dicyclomine into breast milk have been located. The manufacturer has received a case report of apnea in a breastfed 12-day-old infant whose mother was receiving dicyclomine (personal communication, N.G. Dahl, Marion Merrell Dow, Inc., 1992). Following the adverse event, the mother was administered a single, 20-mg dose of the drug and breastfeeding was suspended for 24 hours. Plasma and milk concentrations of dicyclomine 2 hours after the dose were 59 ng/mL and 131 ng/mL (milk:plasma ratio 2.2), respectively. Although a causal relationship between dicyclomine and apnea was not established, similar adverse reactions have occurred when the drug was administered directly to infants (1). Consequently, the safest course is to avoid dicyclomine during nursing.
References
1.Friedman JM, Little BB, Brent RL, Cordero JF, Hanson JW, Shepard TH. Potential human teratogenicity of frequently prescribed drugs. Obstet Gynecol 1990;75:594–9.
2.Product information. Bentyl. Marion Merrell Dow, Inc., 1992.
3.Gibson JP, Staples RE, Larson EJ, Kuhn WL, Holtkamp DE, Newberne JW. Teratology and reproduction studies with an antinauseant. Toxicol Appl Pharmacol 1968;13:439–47.
4.Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
5.Nelson MM, Forfar JO. Associations between drugs administered during pregnancy and congenital abnormalities of the fetus. Br Med J 1971;1:523–7.