USE OF ALLOPURINOL IN PREGNANCY

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(Date of issue: September 2014, Version: 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 allopurinol use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Allopurinol is a hypoxanthine analogue that inhibits xanthine oxidase, thus decreasing the production of uric acid. Allopurinol is used primarily in the management or prophylaxis of gout, uric acid and calcium oxalate renal calculi, and hyperuricaemia associated with cancer chemotherapy. Allopurinol is also occasionally used in the treatment of inflammatory bowel disease and as a thiopurine adjunct in renal transplant recipients.

The conditions for which allopurinol is used are generally rare in women of childbearing age, and human data on allopurinol use during pregnancy are therefore scarce. Pregnancy outcome has been reported in the scientific literature for only 47 first trimester allopurinol exposures, mainly in the form of case reports and small studies. The largest study (n=31) did not report overall malformation rates that were higher than in the general population. However, an unusual and overlapping pattern of malformations, reminiscent of mycophenolate mofetil (MMF) embryopathy, has been observed in two infants exposed to allopurinol in utero. As MMF also disrupts purine biosynthesis, concern has been raised regarding a similar mechanism of teratogenicity for allopurinol. However, a causal association remains to be proven and a genetic basis for the malformations in the two allopurinol-exposed cases has not been fully explored.

Miscarriage rates were not increased above background rates in the cohort described above (n=31), however no other studies have assessed this outcome and an increase in risk of pregnancy loss cannot therefore be excluded. Data are either too limited or are unavailable to permit risk assessments of fetal death, premature delivery, low birth weight, or adverse neurodevelopmental outcomes after exposure to allopurinol during pregnancy.

More research is required before the potential teratogenicity of allopurinol can be confirmed or refuted. In the meantime, allopurinol should only be used during the first trimester of pregnancy where benefits of treatment clearly outweigh the potential risk of birth defects, and provided the available data have been fully discussed with the patient. Women should also be made aware of the lack of data for other outcomes, some of which are relevant for use at any stage of pregnancy.

Other risk factors may be also 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.

It is vital that outcome information is collected for all allopurinol exposed pregnancies and that fetuses or infants with malformations are assessed by a clinical geneticist. Please report any exposed pregnancies to UKTIS using the pregnancy reporting form.

This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to be sure you are using the most up-to-date version.

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.