USE OF CODEINE OR DIHYDROCODEINE IN PREGNANCY

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(Date of issue: October 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 codeine use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Codeine is an opioid analgesic used in the treatment of mild to moderate pain, and as an antitussive. Dihydrocodeine is a semisynthetic opioid also used in the treatment of mild to moderate pain and as an antitussive. There are no pregnancy safety data specifically for dihydrocodeine, however risks are expected to be similar to those for codeine.

There is conflicting evidence regarding the risk of congenital anomaly following in utero codeine exposure. The majority of the available prospective cohort studies have not identified significant increased risks of congenital anomaly following fetal codeine exposure, although one has suggested a possible increase in the risk of respiratory malformations. Retrospective case-control studies have identified associations between maternal codeine use in pregnancy and cardiovascular anomalies. However, the majority of these case-control studies are considered heavily confounded and often analysed the risks associated with maternal codeine exposure as secondary study objectives using small numbers of codeine-exposed infants. Further more robust research is needed before firm conclusions regarding the risk of congenital anomalies can be provided.

There are no data regarding the risk of spontaneous abortion, intrauterine death or offspring neurodevelopment following in utero codeine exposure. Increased use of codeine in pregnancy among mothers of children with neuroblastoma was found in a single study. However, this finding is heavily confounded and as yet an association remains unconfirmed.

There are theoretical concerns that maternal use of codeine near term may be associated with respiratory depression in the neonate. However, the only study which has investigated the risk of neonatal respiratory depression found no increased risk. There are a small number of published case reports of perinatal arterial stroke and neonatal withdrawal in infants of women who used codeine in the weeks before delivery, however no epidemiological studies have investigated these associations. Neonatal monitoring for symptoms of withdrawal may be warranted following maternal use of codeine near term.

The MHRA advise that the use of codeine by lactating mothers is contraindicated due to concerns of infant opiate toxicity following exposure to codeine or its metabolite, morphine, through breast milk. Periods of prolonged codeine use during pregnancy may result in detectable levels of opiates in the breast milk. There are no data relating to the risk posed to the breastfed infant following maternal use of codeine during pregnancy alone, and as such there are no guidelines concerning breastfeeding following prolonged use of codeine during pregnancy.

Exposure to codeine at any stage in 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.