USE OF ALLOPURINOL IN PREGNANCY

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(Date of issue: August 2019, Version: 2)

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, thereby decreasing the production of uric acid. Historically, the main uses of allopurinol were in the management or prophylaxis of gout, uric acid or calcium oxalate renal calculi, and hyperuricaemia associated with cancer chemotherapy. Exposure in females of childbearing age was therefore uncommon. However, use in the treatment of inflammatory bowel disease (and therefore in the potentially childbearing population) is increasing. Allopurinol is also used as a thiopurine adjunct in renal transplant recipients and in the treatment of protozoan infections.

Human data on allopurinol use during pregnancy are scarce. The presence/absence of congenital malformations has been documented in a collective total of 43 live-born infants following first trimester allopurinol exposure, with data provided from retrospective case reports/small series (n=16) and one prospectively-ascertained case series (n=27). Overall, 41 infants were born without major congenital malformations (MCMs). However, the two infants with MCMs (reported by separate sources) had an unusual and overlapping malformation pattern reminiscent of mycophenolate mofetil (MMF) embryopathy. 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 prospective case series described above (n=31). However, conclusions are limited by the small sample size and lack of a control group. As no other studies have assessed this outcome, an increased risk of miscarriage cannot be excluded. Data are either too limited or are unavailable to assess the risk of fetal death, premature delivery, low birth weight, or adverse neurodevelopmental outcomes following exposure to allopurinol.

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. 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.

In view of the potential safety signal described above, additional fetal monitoring may be indicated following first trimester allopurinol exposure, including detailed anomaly scans that focus on the brain, craniofacial structures, abdominal organs, and renal system. 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.

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 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.