Published: 6 June 2013
Publications
Medicines and Use in Pregnancy
Prescriber Update 34(2):18–19
June 2013
There are increasing concerns about the safety of medicines in pregnancy.
Careful consideration and discussion of the risk and benefits of all medicines
are required in the management of pregnant women or women intending to become
pregnant.
All available information about the medicine, as well as any circumstances unique to the patient, should be considered. It is also worth considering any medicines the male partner of a pregnant woman is taking as rarely these may also cause problems (eg, finasteride).
Medicines should only be prescribed in pregnancy when the expected benefits to the mother outweigh any potential risks to the mother and foetus. If possible, medicines should be used at the lowest effective dose for the shortest possible duration.
First-trimester medicine exposure (particularly days 18 to 56 post-conception) is associated with the highest risk of malformation. Use of some medicines in the third trimester may be associated with withdrawal effects in the foetus (eg, SSRIs).
The Australian categorisation system for prescribing medicines in pregnancy is a useful source of information for healthcare professionals considering the risks and benefits of medicines in pregnancy (www.tga.gov.au/hp/medicines-pregnancy.htm).
The categorisation system takes into account the known harmful effects of medicines on the developing baby. This includes the potential to cause birth defects, unwanted pharmacological effects around the time of birth, and/or problems in later life. However, this categorisation system is a guide only and is not intended as a substitute for a prescriber’s advice.
Definitions of the Australian Categories for Prescribing Medicines in Pregnancy
Medicines allocated Category A are considered to be relatively safe for use in pregnancy.
Category A
Medicines 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 foetus
having been observed.
Medicines allocated Category B are subcategorised based on animal data, with human data lacking or inadequate.
Category B1
Medicines 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 foetus having been
observed. Studies in animals have not shown evidence of an increased occurrence
of foetal damage.
Category B2
Medicines 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 foetus having been
observed. Studies in animals are inadequate or may be lacking, but available
data show no evidence of an increased occurrence of foetal damage.
Category B3
Medicines 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 foetus having been
observed. Studies in animals have shown evidence of an increased occurrence
of foetal damage, the significance of which is considered uncertain in humans.
Medicines in Category B do not imply greater safety than medicines in Category C.
Category C
Medicines which, owing to their pharmacological effects (risk based on the
mechanism of action of the medicine), have caused or may be suspected of
causing harmful effects on the human foetus or neonate without causing malformations.
These effects may be reversible.
Medicines in Category D are not absolutely contraindicated during pregnancy. However, there is a higher risk of malformations (eg, many anticonvulsants).
Category D
Medicines which have caused, are suspected to have caused, or may be expected
to cause, an increased incidence of human foetal malformation or irreversible
damage. These medicines may also have adverse pharmacological effects.
Medicines in Category X are absolutely contraindicated in pregnancy with a high risk of permanent damage (eg, medicines are teratogenic).
Category X
Medicines which have such a high risk of causing permanent damage to the
foetus that they should not be used in pregnancy or when there is possibility
of pregnancy.
It should be noted that this system only applies to the recommended therapeutic doses in women. It cannot be applied to situations such as overdose, occupational exposure or other situations where the recommended therapeutic dose has been exceeded.
Additionally, some classes of medicines are exempted from pregnancy categorisation including:
- herbal medicines
- traditional Chinese medicines
- mineral and nutritional supplements
- parenteral nutrition preparations.
This does not imply medicines that are exempt are safe during pregnancy. Rather, data are very limited and insufficient to determine their safety.
Full details of exempted classes of medicines may be found on the Therapeutic Goods Administration website (www.tga.gov.au/hp/medicines-pregnancy-exempt.htm).
The New Zealand Formulary (NZF) uses the Australian categorisation system. In many cases the NZF also provides additional notes. This includes identifying medicines, which are not known to be harmful in pregnancy and identifying medicines, which may have harmful effects in pregnancy with indication of trimester of risk. Further information is available at the NZF website (www.nzformulary.co.nz/).
The Centre for Adverse Reactions Monitoring (CARM) has received a total of 106 reports where a pregnant female has been administered a medicine resulting in a reaction involving the foetus or where a reaction has been noted in the child (Table 1). Many of these reports identified multiple suspect medicines and reactions.
Table 1: Medicines for which five or more reports involving a pregnant female or the child that were received by CARM in the period January 2000 until December 2012
| Medicine | No of reports |
|---|---|
| Sodium Valproate | 10 |
| Paroxetine | 9 |
| Venlafaxine | 8 |
| Citalopram | 6 |
| Fluoxetine | 6 |
The receipt of a report by CARM does not necessarily imply that these medicines
are any less safe than other medicines. There are other important factors
which may stimulate reports (eg, wide use). Vaccines and oral contraceptives
were excluded from this search.
Healthcare professionals are encouraged to report these reactions to CARM and to include as much information as possible to help identify other medicines associated with an increased risk of malformations or withdrawal effects in the foetus.
Further information about how to submit an adverse reaction report can be found on the Medsafe website (www.medsafe.govt.nz/safety/report-a-problem.asp) or on the CARM website (https://nzphvc.otago.ac.nz/report/).
