USE OF MEFENAMIC ACID IN PREGNANCY

PLEASE BE AWARE: The advice about use of NSAIDs in pregnancy has recently changed. It is now recommended that prolonged use of NSAIDs should be avoided after 20 weeks of pregnancy (rather than the 30 weeks discussed throughout this document). For more details, please see the information from the MHRA here. This document is currently under review, and will be updated as soon as possible to include the new advice.

Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic pain (particularly dysmenorrhoea) and in the management of rheumatoid arthritis. 

Use of NSAIDs in pregnancy has been associated with an increased risk of miscarriage, persistent pulmonary hypertension of the newborn (PPHN), oligohydramnios, premature closure of the ductus arteriosus (DA), structural cardiovascular defects and a number of other congenital anomalies, including orofacial clefts. However the available data are limited, confounded and often conflicting; further research is therefore required to define the risk of these outcomes more accurately.

Published data concerning the safety of maternal mefenamic acid use in human pregnancy are limited to a single placebo-controlled randomised clinical trial which investigated mefenamic acid as a tocolytic in late pregnancy. No adverse fetal effects were observed in this study and women receiving mefenamic acid were less likely to deliver preterm than those treated with placebo. However, this study did not provide data concerning the safety of mefenamic acid use in early pregnancy and the study sample was small. Published data are too limited to provide an adequate assessment of the safety of mefenamic acid use in pregnancy.

Exposure to NSAIDs after 30 weeks of gestation has been associated with an increased risk of premature closure of the DA and oligohydramnios. These effects are thought to be mediated by the inhibitory effect of NSAIDs on prostaglandin production. There are conflicting findings regarding the risks of PPHN following antenatal use of NSAIDs. Further evidence is required before this possible association can be confirmed. Where published data concerning the fetal effects of gestational exposure are unavailable or limited, a possible class effect for these associations should be considered for all NSAIDs.

All NSAIDs should, where possible, be avoided during the third trimester. In circumstances where the maternal clinical condition requires treatment with mefenamic acid during the third trimester, discussion with a Fetal Medicine Unit regarding antenatal monitoring for oligohydramnios and ductus arteriosus patency is recommended. Where use of mefenamic acid is being considered at any stage of pregnancy the available pregnancy data should be discussed with the patient to support informed decision-making regarding the risks and benefits of treatment.

Please refer to the NSAID overview monograph for more information. Other risk factors may also be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments. Discussion with UKTIS is recommended for all cases of mefenamic acid exposure in pregnancy.