USE OF TRIMETHOPRIM IN PREGNANCY

View printable version
(Date of issue: December 2013, Version: 2.1)

This is a UKTIS monograph for use by health care professionals. For case-specific advice please contact UKTIS on 0344 892 0909. To report an exposure please download and complete a pregnancy reporting form. Please encourage all women to complete an online reporting form.

A corresponding patient information leaflet on trimethoprim use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Trimethoprim is a selective inhibitor of dihydrofolate reductase that prevents folic acid synthesis in bacteria, thereby preventing DNA replication and conferring antimicrobial properties.  It is available for use as a single agent and in combination with sulfamethoxazole (co-trimoxazole), which also inhibits folate metabolism, producing a synergistic antimicrobial effect.

A recent study has reported an increased overall risk of congenital malformation, and specifically of cardiac and limb defects, amongst offspring of women who were dispensed trimethoprim in the 12 weeks prior to pregnancy.  Studies of use in the first trimester have reported an increased risk of neural tube defects, cleft lip/palate and cardiac defects. However, these studies mainly involved small numbers of exposed women and such associations have not been replicated by others

As trimethoprim is a folic acid antagonist, there are theoretical concerns that use during pregnancy may limit the availability to the fetus of folic acid required for normal development. An increased risk of neural tube defects and other malformations has been reported in the offspring of women who have a low folate status (i.e. established folic acid deficiency or low dietary folic acid intake) or who are already taking known folate antagonists (e.g. antiepileptic drugs or proguanil).  Folate supplementation may reduce these risks, and high dose (5mg) folic acid is therefore recommended in all women treated with trimethoprim during the first trimester as a precautionary measure.

Single studies have also reported an increased risk of spontaneous abortion,  intrauterine death, preeclampsia and placental abruption after trimethoprim use in pregnancy.  No reports regarding neonatal complications, neurodevelopment or carcinogenicity were located.

Trimethoprim is frequently used in combination with the sulphonamide, sulfamethoxazole.  There have been concerns that use of sulphonamide-containing medicines near delivery may increase the risk of hyperbilirubinemia in the neonate, particularly in premature infants or infants with glucose-6-phosphate dehydrogenase deficiency.  However, the majority of population studies do not show an increased risk of neonatal hyperbilirubinemia following in utero sulphonamide exposure, and this may therefore only be a concern in neonates with other risk factors such as those described above.  Further research is required to delineate these risks fully.

The treatment of infection in pregnancy should be guided by the results of culture and sensitivity tests, however if treatment is required before test results become available, then where clinically appropriate, penicillins or cephalosporins may be used.

Therapeutic exposure to trimethoprim for a short period in women with normal folate status who are well nourished is not expected to induce folate deficiency. However, the available data are too limited to state that there is no increased risk of congenital malformation or other adverse pregnancy outcome following therapeutic use in pregnancy.  Exposure to trimethoprim at any stage of pregnancy would not usually be regarded as an indication for any additional fetal monitoring.  However, other risk factors may 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.

This document is regularly reviewed and updated. Only use full UKTIS monographs downloaded directly from TOXBASE.org to be sure you are using the most up-to-date version. The summaries of these monographs are openly available on UKTIS.org.

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to health care professionals at www.toxbase.org.

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to ensure you are using the most up-to-date version.