Is cyclobenzaprine (a muscle relaxant) safe to use during pregnancy?

Cyclobenzaprine in Pregnancy

Primary Recommendation

Cyclobenzaprine should be avoided during pregnancy due to emerging evidence of potential birth defects, particularly cardiac and orofacial malformations, despite its FDA Pregnancy Category B classification. 1, 2

Evidence Assessment

FDA Classification vs. Recent Research

• The FDA classifies cyclobenzaprine as Pregnancy Category B, indicating animal studies showed no harm but adequate human studies are lacking 1
• However, the most recent and highest quality human study (2023) found significant associations between periconceptional cyclobenzaprine exposure and multiple birth defects 2
• This study analyzed 33,615 cases and 13,110 controls across 10 U.S. states, representing the largest dataset on cyclobenzaprine pregnancy exposure to date 2

Specific Birth Defect Risks Identified

The 2023 National Birth Defects Prevention Study found elevated risks for:

• Cardiac defects: d-transposition of great arteries (OR 6.97), coarctation of aorta (OR 5.58), pulmonary valve stenosis (OR 4.55), and secundum atrial septal defect (OR 3.08) 2
• Orofacial defects: cleft palate (OR 4.79) and cleft lip (OR 2.50) 2
• Gastrointestinal defects: anorectal atresia/stenosis (OR 6.91) 2

Critical Limitations

• Cyclobenzaprine use during pregnancy is rare (0.15% in cases, 0.07% in controls), resulting in wide confidence intervals 2
• The study estimates are unadjusted for confounders and should be interpreted cautiously 2
• The FDA label acknowledges that "animal reproduction studies are not always predictive of human response" 1

Clinical Decision Algorithm

When Muscle Relaxation is Needed

1. First-line approach: Consider non-pharmacological interventions (physical therapy, heat/cold therapy, rest)
2. If medication required: Use alternatives with better-established safety profiles 3
3. Short-term pain management: NSAIDs (ibuprofen) may be used for 7-10 days in first and second trimesters only, but must be discontinued after gestational week 28 4
4. If cyclobenzaprine exposure has already occurred: Individual risk assessment is required, as the absolute risk remains low given the rarity of exposure 2

Safer Alternatives During Pregnancy

While no muscle relaxant has extensive pregnancy safety data, consider:

• Acetaminophen for pain management throughout pregnancy (good safety record) 5
• Physical modalities as first-line treatment
• Consultation with maternal-fetal medicine if muscle relaxation is medically necessary 3

Critical Pitfalls to Avoid

• Do not rely solely on FDA Category B classification when recent epidemiological data suggests potential harm 1, 2
• Do not use NSAIDs after 28 weeks gestation due to risks of oligohydramnios and premature ductus arteriosus closure 4
• Do not fail to discuss alternative treatment options with better established safety profiles 3
• Do not prescribe without informed consent about the emerging evidence of potential birth defects 2

Lactation Considerations

• It is unknown whether cyclobenzaprine is excreted in human milk 1
• Because cyclobenzaprine is structurally related to tricyclic antidepressants (some of which are excreted in breast milk), caution is warranted during breastfeeding 1
• A decision should be made whether to discontinue nursing or the medication based on benefit-risk assessment 1

Key Takeaway

The 2023 epidemiological evidence showing associations with multiple birth defects (particularly cardiac malformations with odds ratios exceeding 5.0) outweighs the reassuring animal data that led to the Category B classification. In real-world clinical practice, when muscle relaxation is needed during pregnancy, safer alternatives or non-pharmacological approaches should be prioritized. 2