Is dicyclomine safe to use during the first trimester of pregnancy?

Dicyclomine Safety in First Trimester

Dicyclomine can be used during the first trimester of pregnancy, as epidemiologic studies show no increased risk of structural malformations at doses up to 40 mg/day, and the FDA classifies it as Pregnancy Category B. 1

FDA Drug Label Evidence

The FDA label for dicyclomine provides the most authoritative guidance for this question:

• Epidemiologic studies specifically evaluated first-trimester exposure to dicyclomine at doses up to 40 mg/day and found no increased risk of structural malformations in babies born to exposed women 1
• The drug is classified as Pregnancy Category B, meaning adequate and well-controlled studies have not been conducted at the recommended therapeutic doses (80-160 mg/day), but available human data at lower doses are reassuring 1
• Animal reproduction studies in rats and rabbits at doses up to 33 times the maximum recommended human dose showed no evidence of fetal harm 1

Historical Safety Data from Bendectin

Dicyclomine was a component of Bendectin (doxylamine/dicyclomine/pyridoxine), which has extensive safety data:

• A comprehensive meta-analysis of 16 cohort and 11 case-control studies found no association between Bendectin exposure in the first trimester and birth defects, with a pooled relative risk of 0.95 (95% CI 0.88-1.04) for any malformation 2
• Separate analyses for specific defect categories (cardiac, CNS, neural tube, limb reductions, oral clefts, genital tract) all showed relative risks ranging from 0.81 to 1.11, with confidence intervals including unity 2
• This represents one of the most thoroughly studied medication exposures in pregnancy 2

Clinical Dosing Considerations

The key distinction is between studied doses and therapeutic doses:

• Human epidemiologic safety data exist for doses up to 40 mg/day during the first trimester 1
• Standard therapeutic dosing is 80-160 mg/day, which has not been studied in adequate controlled trials during pregnancy 1
• The FDA label states the drug "should be used during pregnancy only if clearly needed" at therapeutic doses 1

Common Pitfalls to Avoid

• Do not assume all anticholinergic/antispasmodic agents have equivalent safety profiles - each must be evaluated individually based on available human data
• Do not confuse the reassuring data at 40 mg/day with automatic safety at higher therapeutic doses (80-160 mg/day), though the animal data at 33× human doses provides additional reassurance 1
• Recognize that Pregnancy Category B does not mean "proven safe" - it means animal studies show no risk but human studies are lacking at therapeutic doses, though lower-dose human data are reassuring 1

Practical Clinical Algorithm

When considering dicyclomine in the first trimester:

1. If the indication is mild and non-urgent: Consider alternative therapies with more robust first-trimester safety data at therapeutic doses
2. If dicyclomine is clinically necessary: Use the lowest effective dose, ideally ≤40 mg/day where human safety data exist 1
3. If higher doses (80-160 mg/day) are required: The benefit must clearly outweigh theoretical risks, as these doses lack controlled human studies despite reassuring animal data 1
4. Document shared decision-making regarding the available evidence and the distinction between studied and therapeutic doses 1