Is dicyclomine (anticholinergic medication) safe to use during pregnancy?

Dicyclomine Use in Pregnancy

Dicyclomine is classified as FDA Pregnancy Category B and can be used during pregnancy when clearly needed, though epidemiologic safety data only support doses up to 40 mg/day during the first trimester, which is substantially lower than the typical therapeutic dose of 80-160 mg/day. 1

FDA-Approved Safety Profile

The FDA drug label provides the most authoritative guidance on dicyclomine use in pregnancy:

• Adequate and well-controlled studies have not been conducted at the recommended therapeutic doses of 80-160 mg/day 1
• Epidemiologic studies showed no increased risk of structural malformations in babies born to women taking dicyclomine at doses up to 40 mg/day during the first trimester 1
• Animal reproduction studies in rats and rabbits at doses up to 33 times the maximum human dose revealed no evidence of fetal harm 1
• The drug should be used during pregnancy only if clearly needed 1

Critical Safety Concerns

Dose-Dependent Risk Gap

There is a significant evidence gap between the doses studied epidemiologically (≤40 mg/day) and standard therapeutic doses (80-160 mg/day), meaning safety at therapeutic doses remains unestablished 1. This creates clinical uncertainty when prescribing at effective doses.

Emerging Long-Term Risk Signal

A 2023 multigenerational cohort study found concerning evidence that in utero exposure to Bendectin (which contained dicyclomine in the 1960s formulation) was associated with a 3.4-fold increased risk of adult-onset colorectal cancer in offspring (adjusted HR = 3.38,95% CI: 1.69-6.77) 2. While this finding requires experimental confirmation and may be specific to the historical three-drug formulation, it raises questions about long-term offspring outcomes that warrant consideration.

Contraindication in Breastfeeding

Dicyclomine is absolutely contraindicated in breastfeeding women 1. The drug is excreted in human milk and has been associated with serious respiratory symptoms, seizures, syncope, and death in infants less than 6 months of age, though causality has not been definitively established 1.

Clinical Decision Algorithm

When dicyclomine is being considered for pregnancy:

1. First, evaluate if safer alternatives exist for the indication (e.g., for nausea/vomiting of pregnancy, doxylamine-pyridoxine without dicyclomine is preferred) 3

2. If dicyclomine is necessary:

   • Use only if clearly needed and benefits outweigh risks 1
   • Limit to ≤40 mg/day if possible, as this is the only dose range with epidemiologic safety data 1
   • Recognize that therapeutic efficacy at this lower dose may be suboptimal

3. Avoid in the first trimester when possible, as this is the period of organogenesis and highest teratogenic risk 4

4. Plan for discontinuation before delivery to avoid neonatal anticholinergic effects

5. Counsel patients about the limited safety data at therapeutic doses and the emerging (though unconfirmed) signal regarding long-term offspring cancer risk 2

Common Pitfalls to Avoid

• Do not assume Category B means "safe" - it only means animal studies showed no risk, but human data at therapeutic doses are lacking 1
• Do not prescribe standard therapeutic doses (80-160 mg/day) without explicit informed consent about the lack of safety data at these doses 1
• Do not continue dicyclomine into the postpartum period if breastfeeding is planned - it is absolutely contraindicated 1
• Do not overlook safer alternatives for common pregnancy conditions like nausea/vomiting, where doxylamine-pyridoxine (without dicyclomine) has extensive safety data in over 200,000 exposed pregnancies 3