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

Is Dicyclomine Safe in the First Trimester?

Dicyclomine is considered safe for use during the first trimester of pregnancy based on FDA classification as Pregnancy Category B, with epidemiologic studies showing no increased risk of structural malformations at doses up to 40 mg/day. 1

FDA Drug Label Evidence

The FDA drug label for dicyclomine provides the most authoritative guidance:

• Epidemiologic studies demonstrated no increased risk of structural malformations among babies born to women who took 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 recommended human dose (160 mg/day) revealed no evidence of harm to the fetus. 1

• The drug is classified as Pregnancy Category B, meaning adequate and well-controlled studies have not been conducted in pregnant women at recommended doses (80-160 mg/day), but available evidence is reassuring. 1

Supporting Research Evidence

Multiple epidemiologic studies support the safety profile:

• A meta-analysis of 16 cohort and 11 case-control studies examining Bendectin (which contained dicyclomine, doxylamine, and pyridoxine) found a pooled relative risk of 0.95 (95% CI 0.88-1.04) for any malformation at birth with first-trimester exposure. 2

• A prospective study of 620 pregnant women prescribed Debendox (dicyclomine-doxylamine-pyridoxine) during the first 13 weeks showed 95% had normal pregnancy outcomes, with a malformation rate of 2.0% compared to 2.0% in unexposed women. 3

• For specific malformation categories, the meta-analysis found relative risks ranging from 0.81 for oral clefts to 1.11 for limb reductions, with all 95% confidence intervals including unity (no increased risk). 2

Important Caveats and Considerations

One recent concern requires mention:

• A 2023 multigenerational cohort study found higher colorectal cancer risk in adult offspring exposed in utero to Bendectin (adjusted HR 3.38,95% CI 1.69-6.77), though this may be driven by the dicyclomine component. 4 However, this represents a single study examining long-term outcomes decades later, not immediate pregnancy outcomes or congenital malformations.

Practical prescribing guidance:

• The FDA label states dicyclomine "should be used during pregnancy only if clearly needed," reflecting the Category B classification where animal studies are reassuring but human data at therapeutic doses are limited. 1

• Dicyclomine is contraindicated in breastfeeding women and infants under 6 months due to serious respiratory complications reported in infants. 1

Clinical Algorithm for First Trimester Use

When considering dicyclomine in the first trimester:

1. Confirm the indication is appropriate (irritable bowel syndrome with spasmodic abdominal pain). 5

2. Use the lowest effective dose (epidemiologic safety data supports doses up to 40 mg/day). 1

3. Document informed consent discussing Category B classification and available safety data. 1

4. Avoid in women planning to breastfeed given the absolute contraindication. 1

5. Exercise additional caution in patients with renal impairment, as the drug is substantially excreted by the kidney. 1

Common Pitfalls to Avoid

• Do not assume all antispasmodics have equivalent safety profiles in pregnancy—each medication requires individual assessment. 1

• Do not confuse the historical Bendectin formulation studies with current dicyclomine monotherapy—the combination product contained multiple active ingredients. 2, 3

• Do not prescribe to breastfeeding mothers under any circumstances—this is an absolute contraindication. 1