Is mefenamic acid (nonsteroidal anti-inflammatory drug (NSAID)) safe to use during pregnancy?

Mefenamic Acid Is NOT Teratogenic

Mefenamic acid is not teratogenic—it does not cause birth defects or structural malformations—but it is contraindicated in pregnancy, particularly after 20 weeks gestation, due to serious fetotoxic effects including oligohydramnios, premature ductus arteriosus closure, and neonatal renal impairment. 1

Understanding the Distinction: Teratogenic vs. Fetotoxic

The critical distinction here is that mefenamic acid causes fetotoxicity (harm to the developing fetus through functional impairment), not teratogenicity (structural birth defects during organogenesis). 1

• No evidence of structural malformations: Animal studies in rats at 1.6-times the maximum recommended human dose (MRHD) and rabbits at 0.6-times the MRHD showed no clear adverse developmental effects or structural abnormalities. 1
• Clinical data supports lack of teratogenicity: A 1992 randomized controlled trial of mefenamic acid 500mg three times daily in pregnant women at risk of premature labor reported "no cases of foetal malformations in either of the groups." 2

Specific Risks by Gestational Age

After 30 Weeks Gestation (Third Trimester)

• Premature closure of fetal ductus arteriosus is the primary concern with NSAID use at approximately 30 weeks gestation or later. 1
• This risk is shared by all NSAIDs and represents a class effect, not specific to mefenamic acid. 3

After 20 Weeks Gestation (Late Second/Third Trimester)

• Oligohydramnios (reduced amniotic fluid) can occur as early as 48 hours after NSAID initiation, though typically develops after days to weeks of treatment. 1
• Neonatal renal impairment may result from fetal renal dysfunction, with some cases requiring dialysis or exchange transfusion. 1
• A 2025 cohort study of over 1 million children found mefenamic acid exposure in the second trimester was associated with increased childhood chronic kidney disease risk (weighted HR 1.29; 95% CI 1.15-1.46). 4

First Trimester and Early Second Trimester

• No increased risk of miscarriage or structural birth defects with early pregnancy exposure to NSAIDs, including mefenamic acid. 3, 5
• Fertility concerns: NSAIDs can interfere with ovulation by inducing luteinized unruptured follicle syndrome, potentially reducing fertility in women trying to conceive. 3, 1

Clinical Algorithm for Mefenamic Acid Use in Women of Reproductive Age

Women Actively Trying to Conceive

• Discontinue mefenamic acid completely due to interference with ovulation and blastocyst implantation. 6, 1
• Switch to acetaminophen at the lowest effective dose for pain management. 6

First Trimester (Weeks 0-13)

• Avoid if possible, but exposure does not necessitate pregnancy termination as there is no teratogenic risk. 1, 5
• If NSAID use is absolutely necessary, ibuprofen has the most reassuring safety data, not mefenamic acid. 3, 7
• Use lowest effective dose for shortest duration (maximum 7-10 days). 3

Second Trimester Before 20 Weeks (Weeks 14-19)

• Use with extreme caution only if benefits clearly outweigh risks. 1
• Prefer ibuprofen over mefenamic acid if NSAID is required. 3, 7
• Limit to 7-10 days at lowest effective dose. 3

After 20 Weeks Gestation

• Contraindicated. 1
• If use extends beyond 48 hours, monitor with ultrasound for oligohydramnios. 1
• If oligohydramnios occurs, discontinue immediately and follow up according to clinical practice. 1

After 28-30 Weeks Gestation

• Absolutely contraindicated due to high risk of premature ductus arteriosus closure. 3, 7, 1

Safer Alternatives During Pregnancy

• First-line: Acetaminophen at lowest effective dose for shortest duration. 7
• If NSAID required in first/second trimester: Ibuprofen 200-400mg every 6-8 hours (maximum 7-10 days), which has the most reassuring safety data among NSAIDs. 3, 7
• For chronic inflammatory conditions: Transition to pregnancy-compatible alternatives including hydroxychloroquine, sulfasalazine (with folate supplementation), low-dose prednisone (≤10mg daily), azathioprine, or colchicine. 3

Common Pitfalls to Avoid

• Don't confuse "contraindicated" with "teratogenic": Many clinicians and patients mistakenly believe contraindication in pregnancy automatically means the drug causes birth defects. Mefenamic acid's contraindication is based on fetotoxic effects (functional harm), not teratogenic effects (structural malformations). 1
• Don't rely on the traditional "third trimester" designation: The critical cutoff is 28-30 weeks gestation, not the traditional third trimester boundary, as fetal sensitivity increases significantly after this point. 7, 1
• Don't overlook over-the-counter NSAID use: Many women don't realize mefenamic acid and other NSAIDs are contraindicated and may not report their use—proactive questioning is essential. 6
• Don't assume all NSAIDs carry equal risk profiles: While all NSAIDs share similar late-pregnancy risks, ibuprofen has substantially more reassuring safety data for early pregnancy use compared to mefenamic acid. 3, 7

Breastfeeding Considerations

• Trace amounts of mefenamic acid may be present in breast milk. 1
• A decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. 1
• Most NSAIDs, including ibuprofen, are considered safe during breastfeeding as they transfer in low amounts to breast milk. 7