Is mefenamic acid (NSAID) safe to use during pregnancy?

Mefenamic Acid During Pregnancy

Mefenamic acid should be avoided during pregnancy, particularly after 20 weeks gestation, and is absolutely contraindicated after 30 weeks due to serious fetal risks including premature closure of the ductus arteriosus, oligohydramnios, and neonatal renal impairment. 1

Safety Profile by Trimester

First Trimester (Before 20 Weeks)

• Early pregnancy exposure to NSAIDs, including mefenamic acid, shows no clear evidence of increased risk of miscarriage or teratogenicity 2, 3
• Data from observational studies regarding embryofetal risks in the first trimester are inconclusive 1
• Animal studies show increased pre- and post-implantation loss with prostaglandin synthesis inhibitors like mefenamic acid 1

Second Trimester (20-28 Weeks)

• Use after 20 weeks gestation has been associated with fetal renal dysfunction leading to oligohydramnios 1
• If absolutely necessary between 20-30 weeks, limit to the lowest effective dose for the shortest duration (maximum 7-10 days) 2, 3
• If treatment extends beyond 48 hours after 20 weeks, ultrasound monitoring for oligohydramnios is necessary 1
• One case report documented ductus arteriosus constriction and oligohydramnios in the late second trimester after long-term NSAID exposure 4
• Short-term use (a few days) in the second trimester does not appear to pose relevant risk, but prolonged use in the advanced second trimester may cause complications similar to third trimester exposure 4

Third Trimester (After 28-30 Weeks)

• Mefenamic acid is contraindicated after approximately 30 weeks gestation 1
• Use at 30 weeks or later increases risk of premature closure of the fetal ductus arteriosus 1
• Additional risks include oligohydramnios, neonatal renal impairment, and pulmonary hypertension in the newborn 3, 1
• Animal studies showed increased perinatal death and delayed parturition 1

Specific Fetal Risks

Cardiovascular Effects

• Premature closure of the ductus arteriosus occurs with use at approximately 30 weeks or later 1
• Ductus arteriosus constriction was documented in 0.5% of pregnancies exposed in second/third trimester versus 0% in first trimester only exposure 4

Renal Effects

• Fetal renal dysfunction leading to oligohydramnios can occur as early as 20 weeks gestation 1
• Oligohydramnios occurred in 3.8% of second/third trimester exposures versus 2.5% in first trimester only exposure 4
• In some cases, neonatal renal impairment has been irreversible, requiring exchange transfusion or dialysis 1
• Oligohydramnios has been reported as soon as 48 hours after NSAID initiation, though typically occurs after days to weeks of treatment 1

Other Adverse Outcomes

• Pulmonary hypertension in the newborn is a potential risk 3
• Animal data showed smaller litter sizes and higher perinatal death rates 1

Clinical Management Recommendations

If Use Is Being Considered

• Avoid mefenamic acid entirely after 30 weeks gestation 1
• Between 20-30 weeks, use only if absolutely necessary at the lowest effective dose for shortest duration 1
• If treatment extends beyond 48 hours after 20 weeks, perform ultrasound monitoring for oligohydramnios 1
• If oligohydramnios develops, discontinue mefenamic acid immediately and follow up according to clinical practice 1

If Exposure Has Already Occurred

• For third trimester exposure: immediate discontinuation and fetal assessment for ductal constriction and oligohydramnios is necessary 3
• Monitor for signs of fetal renal dysfunction and cardiovascular complications 1

Safer Alternatives for Pain Management

For women requiring anti-inflammatory or analgesic treatment during pregnancy, pregnancy-compatible alternatives include:

• Acetaminophen is generally considered safe during any trimester and is used by approximately 65% of pregnant women 5
• Low-dose glucocorticoids (≤10 mg daily prednisone) for inflammatory conditions 3
• Hydroxychloroquine for rheumatologic conditions 2, 3
• Sulfasalazine (with folate supplementation) for inflammatory conditions 2, 3
• Azathioprine for inflammatory conditions 2, 3
• Colchicine at doses of 1-2 mg/day 2, 3

Additional Considerations

Fertility Effects

• Mefenamic acid may delay or prevent rupture of ovarian follicles, causing reversible infertility 1
• Women actively trying to conceive should avoid NSAIDs or use them only intermittently 3
• Animal studies showed decreased corpora lutea and fertility at therapeutic doses 1

Breastfeeding

• 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, considering the importance of the drug to the mother 1

Drug Interactions

• Mefenamic acid prolongs prothrombin time and has synergistic bleeding effects with anticoagulants like warfarin 1
• Concomitant use with antacids containing magnesium hydroxide increases mefenamic acid levels by 125% (Cmax) and 36% (AUC), potentially increasing adverse effects 1