Prescribing medicines in pregnancy

An Australian categorisation of risk of drug use in pregnancy

This document is currently being updated, and will become a web based resource containing more complete and relevant information to be taken into account by health professionals and patients in reaching difficult and complex decisions about use of medicines in pregnancy. At present, the Commonwealth does not warrant that the information is accurate, comprehensive or up-to-date and you should make independent inquiries, and obtain appropriate advice, before relying on the information in any important matter. Enquiries on the content of the material should directed to the Therapeutic Goods Administration.

Printable version of Prescribing Medicines in Pregnancy

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Prescribing medicines in pregnancy, 4th edition, 1999 (pdf,447kb)*

*NOTE: Drugs approved since 1999 are in the amendment documents below. Please search all documents. For more information, consult the Product Information for the medicine you are searching for.

Amendments to Prescribing medicines in pregnancy, 4th edition

Online version of Prescribing Medicines in Pregnancy

Copyright
From the chairman
Introduction
Australian categorisation of drugs <http://www.tga.gov.au/docs/html/mip/medicine.htm>
Appendixes
- A. Therapeutic goods exempted from pregnancy classification <http://www.tga.gov.au/docs/html/mip/exempt.htm>
- B. Obstetric Drug Information Services <http://www.tga.gov.au/docs/html/mip/odis.htm>

Copyright

ISBN 0 642 41553 6

This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth available from AusInfo. Requests and inquiries concerning reproduction and rights should be addressed to the Manager, Legislative Services, AusInfo, GPO Box 1920, Canberra ACT 2601.

First published 1989

Second edition 1992

Reprinted 1994

Third edition 1996

Fourth edition 1999

Prepared by the Medicines in Pregnancy Working Party of the Australian Drug Evaluation Committee (printing partially funded by the Pharmaceutical Education Program).

Enquiries should be directed to

Publications Unit
TGA
PO Box 100
Woden ACT 2606

Publications approval number 2637

From the Chairman

It is now ten years and four editions since Medicines in Pregnancy was first produced by the Australian Drug Evaluation Committee to assist health professionals in the appropriate prescription of drugs in pregnancy. Over one hundred new medicines have been evaluated and approved for registration in Australia since the publication of the last edition in 1996 and have been added to the current booklet. In addition, the introduction of colour printing has allowed a revision of the layout of the text to improve the clarity of information provided.

This edition has been retitled Prescribing Medicines in Pregnancy, to emphasise the purpose of the booklet - guiding the prescriber in the correct choice of medication when drug therapy is required in pregnancy. This booklet is not intended for use in the more complex situation of inadvertent drug exposure in early pregnancy, and for this circumstance, the reader is referred to the Obstetric Drug Information Services listed in Appendix B.

The Australian Drug Evaluation Committee is keen to ensure that appropriate therapeutic options are available to all women needing medical treatment or preventative therapy during pregnancy, with minimisation of any associated risk to the fetus. An essential prerequisite, and the aim of this booklet, is the provision of accurate, concise information as a basis for informed consent and rational decision making. As always, the Committee welcomes feedback and is most grateful to those who have offered constructive suggestions about past editions.

Dr Rosemary Ayton
Chairman
Medicines in Pregnancy Working Party

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Introduction

One in twenty five (1:25) babies born in this country has a birth defect. A small proportion of these birth defects are caused by medications taken by the mother during pregnancy.

This categorisation is intended to provide information which can be used by health professionals as the basis for rational decision making when planning the medical management of pregnant patients or those intending to become pregnant. Therefore, in many cases, this categorisation will not be appropriate as the sole basis of decision making after inadvertent or accidental drug exposure has occurred during pregnancy. In this context, there can be no substitute for expert information based on a rigorous appraisal of all the specific circumstances in each case. Appendix B should be used to ensure that appropriate advice is obtained in such situations. This categorisation applies only to recommended therapeutic doses in women in the reproductive age group. In situations such as overdose, occupational exposure and others when the recommended therapeutic dose is exceeded, it cannot be assumed that the classifications assigned to individual medicines are valid.

Most medicines cross the placenta. This categorisation has taken into account the known harmful effects of medicines on the developing baby, including the potential to cause birth defects, the potential to cause unwanted pharmacological effects around the time of birth (effects which may or may not be reversible), and the potential to cause problems such as cancer in later life. However, it does not take into account the rare circumstance of an idiosyncratic reaction in the neonate to a medicine which crosses the placenta.

All gestational ages referred to in this booklet are based on the time of conception. A medicine may have more than one harmful effect on the developing baby depending on the timing of exposure. During the first two weeks of development, from conception to the first missed period, the embryo is thought to be resistant to any teratogenic effects of medicines. The critical period of embryonic development, when the organ systems develop, starts at about 17 days post-conception and is complete by 60-70 days. Exposure to certain medicines during this period (17-70 days) can cause major birth defects. In general, exposure to medicines beyond 70 days post-conception is not associated with the induction of major birth defects.

However, some medicines can interfere with functional development of organ systems in the second and third trimesters and produce serious consequences. An important example is renal dysfunction in the fetus caused by ACE inhibitors taken during the second and third trimesters.

Also, the developing central nervous system, because of its prolonged period of histogenesis and functional maturation, can be damaged by exposure to certain medicines in the second and third trimesters, resulting in problems such as mental retardation, cerebral palsy or deafness.

In addition to gestational timing, the actual dose being given, compared to a known harmful dose, needs to be considered in assessing whether there are likely to be any adverse effects.

The list of categorised medicines includes most of those used commonly in Australia. The categorisation is based on currently available evidence and changes may be necessary from year to year as new evidence is presented and analysed. The class statements in italicised blue font should be considered integral information about all of the drugs covered in that class.

For pharmaceutical products containing two or more active medicines, the categorisation of the combination is based on the component for which the categorisation is most restrictive. When a medicine is only to be used in men, it will not be found in the booklet although it will have a pregnancy category in the Product Information.

The Australian categorisation consists of the following categories:

Category A

Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.

Category C

Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

Category B1

Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.

Studies in animals have not shown evidence of an increased occurrence of fetal damage.

Category B2

Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.

Category B3

Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

Category D

Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

Category X

Drugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy.

Note: For drugs in the B1, B2 and B3 categories, human data are lacking or inadequate and subcategorisation is therefore based on available animal data. The allocation of a B category does NOT imply greater safety than the C category. Drugs in category D are not absolutely contraindicated in pregnancy (e.g. anticonvulsants). Moreover, in some cases the 'D' category has been assigned on the basis of 'suspicion'.

Due to legal considerations in this country, sponsor companies have, in some cases, applied a more restrictive category than can be justified on the basis of the available data.

In some cases there may be discrepancies between the published Product Information and the information in this booklet due to the process of ongoing document revision.