USE OF IMATINIB IN PREGNANCY

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(Date of issue: August 2015, 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 imatinib use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Imatinib mesylate is a tyrosine kinase inhibitor used in the treatment of haematological malignancies (specifically Philadelphia chromosome positive chronic myeloid leukaemia (CML) or acute lymphoblastic leukaemia (ALL)), Kit (CD117) positive gastrointestinal stromal tumours, and other malignancies. Imatinib inhibits signalling and proliferation of cells driven by dysregulated platelet-derived growth factor receptor (PDGFR) and Abl kinase activity.

Data regarding imatinib use in human pregnancy are limited to retrospective case reports and case series describing approximately 240 pregnancies, 149 of which were exposed in the first trimester. No epidemiological studies have assessed the risk of congenital malformation, spontaneous abortion, intrauterine death, low birth weight, preterm delivery, neonatal complications or adverse neurodevelopmental outcomes following in utero imatinib exposure. 

Both animal studies and human case reports have described malformations in fetuses exposed to imatinib during organogenesis. Certain anomalies (combinations of exomphalos, renal agenesis, scoliosis and hemivertebrae) have been reported in four infants in the published literature, and in one infant reported retrospectively to UKTIS. Although duplicate reporting of the same case is possible, and investigation for a genetic cause was not undertaken in any of these cases,    further investigation is warranted to determine if these reports signal a pattern of malformation attributable to in utero imatinib exposure. Intrauterine growth restriction has also been observed in case reports following third trimester imatinib exposure.

The potential teratogenicity of imatinib and other tyrosine kinase inhibitors requires that their use in pregnancy be carefully considered against the need to prevent deterioration of the maternal disease. Patients wishing to interrupt therapy to become pregnant should also be informed of the risk of relapse even where complete molecular remission was achieved, and of the possibility of a suboptimal response on restarting therapy. Imatinib should only be used during the first trimester of pregnancy where benefits of treatment clearly outweigh the potential risk of congenital malformation, and where these risks and benefits have been fully discussed with the patient. Due to the lack of data, additional fetal monitoring for structural malformation and growth may be warranted on a case-by-case basis. 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.

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.