USE OF DICLOFENAC IN PREGNANCY

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic pain (including 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.

Twelve studies collectively including approximately 15,000 unique diclofenac-exposed pregnancies have investigated the risk of adverse fetal effects following in utero exposure. These studies have provided conflicting evidence, with a small number describing statistically significant increased risks of miscarriage, cardiovascular malformation, and abnormal birth weight outcomes. However, it is possible that these results may have been produced as a result of data confounding. Further studies using additional datasets are required before robust conclusions can be drawn concerning the fetal effects of maternal diclofenac use in pregnancy.

No evidence of associations with intrauterine death/stillbirth or preterm delivery has been provided from a small number of studies. No controlled studies investigating neurodevelopmental impairment or malignancy risks were located.

Exposure to NSAIDs after 20 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 have been case reports of premature closure of the DA occurring after a single dose of diclofenac and following use of a topical preparation. There are also 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 after twenty weeks of pregnancy. In circumstances where the maternal clinical condition requires short-term treatment with diclofenac (such as acute short-lived pain: post-operative, dental, skeletal injury), treatment should be limited to the shortest duration possible. There is currently no evidence-based guidance about how long use should be restricted for, but pragmatic advice is to limit use to no longer than 3 days. Longer term use, for example for treatment of chronic arthritis, should be avoided. As fetal urine production begins at approximately 10 weeks’ gestational age, referral to a Fetal Medicine Unit for monitoring of DA patency and oligohydramnios is recommended following prolonged NSAID use after the first trimester.

Where use of diclofenac 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 diclofenac exposure in pregnancy.