Published: 2 December 2021

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REMINDER: Avoid teratogenic medicines in pregnancy

Published: 2 December 2021
Prescriber Update 42(4): 46–48
December 2021

Use of medicines in pregnancy is common

Medicine exposure during pregnancy is common^1–4 and increasing.³ A recent study of prescription medicine dispensing patterns in pregnant women in New Zealand found that 67.2 percent of pregnancies in 2015 were exposed to a non-supplement prescription medicine.³

Use of medicines during pregnancy may be necessary to manage underlying chronic conditions (eg, diabetes mellitus, asthma, epilepsy), acute illness (eg, infection), or a pregnancy-related condition (eg, hyperemesis, gestational diabetes, hypertension, deep vein thrombosis). Treating such conditions is important for both maternal and fetal health.

Medicine exposure in pregnancy may occur inadvertently as over half of pregnancies in New Zealand are unplanned.⁵

Prescribing medicines to people of childbearing potential

Consider the possibility of pregnancy when prescribing medicines for a person of childbearing potential. If possible, select a therapeutic option that would be safe in pregnancy.

For short-term treatments, use the lowest effective dose for the shortest possible time to limit the possibility of exposure in the event of an unplanned pregnancy.

The New Zealand Formulary and the New Zealand data sheets are useful sources of information about medicine use in pregnancy.

Avoid teratogenic medicines in people of childbearing potential

Teratogenic medicines should be avoided in people of childbearing potential whenever possible.

If it is necessary to prescribe a teratogenic medicine to a person of childbearing potential, the person must be fully informed of the nature and level of risk of harm to the fetus if pregnancy occurs.

Pregnancy must be excluded before starting treatment with the teratogenic medicine. The person must use effective contraception without interruption from one month before treatment, for the duration of treatment and for a specified period (depending on the medicine) after stopping treatment. The period for continuing pregnancy prevention measures after treatment cessation varies for different medicines and is specified in the data sheet.

For example, pregnancy prevention measures must continue to be used for one month after stopping treatment with isotretinoin (Oratane).⁶ The person must not become pregnant for three years (36 months) after stopping treatment with acitretin (Novatretin).^7,8

See section 4.4 of the data sheet for detailed pregnancy prevention measures. Medsafe publishes pharmaceutical company data sheets on the Medsafe website.

• Search for a data sheet

Pharmaceutical companies may also publish educational materials for healthcare professionals and people about the risk of exposure in pregnancy. Educational materials are available for:

• Epilim (sodium valproate)
• Oratane (isotretinoin).

People should avoid unplanned pregnancy while taking a teratogenic medicine

People on treatment with a teratogenic medicine for a defined length of time, such as isotretinoin for acne, must defer pregnancy until after treatment.

Some people will want to have a child whilst taking a long-term teratogenic medicine such as sodium valproate. This requires careful planning before pregnancy to limit the risk of harm to the fetus and enable optimal treatment for the person during pregnancy.⁹

Sodium valproate for the treatment of bipolar disorder is contraindicated in pregnancy. A person on sodium valproate for bipolar disorder should be reviewed by a specialist experienced in the management of bipolar disorder and switched to a suitable alternative treatment prior to pregnancy.^10,11

In the treatment of epilepsy, sodium valproate is contraindicated in pregnancy unless there is no suitable alternative treatment.¹⁰ For these people, pregnancy must be carefully planned, including referral to a specialist experienced in the management of epilepsy for advice, prior to conception.¹⁰

If an unplanned pregnancy occurs while on treatment with sodium valproate, urgent specialist consultation is required to reassess the benefits and risks of continuing the medicine. Sudden discontinuation of antiepileptic therapy should be avoided as it may lead to breakthrough seizures, which could have serious consequences for both the person and fetus.^10,12

Use of teratogenic medicine by male partner

For some medicines, the teratogenic risk also extends to use by a male partner. For example, lenalidomide, which is indicated for the treatment of multiple myeloma and myelodysplastic disorders, is structurally related to thalidomide. Lenalidomide is present in semen during treatment. Males on treatment with lenalidomide must comply with contraception requirements detailed in the data sheet.¹³

Interactions with contraception

Caution is needed if prescribing a medicine that may interfere with contraceptive effectiveness in a person who is on treatment with a teratogenic medicine.

Medicines that induce hepatic metabolism by the CYP3A4 enzyme (eg, rifampicin, carbamazepine, phenytoin, St John’s wort, topiramate) reduce the effectiveness of oral hormonal contraceptives.¹⁴

People taking a teratogenic medicine should also be aware that diarrhoea and vomiting reduce the absorption of oral hormonal contraceptive pills, which may result in contraceptive failure.¹⁴ They should seek medical advice on how to manage this situation.

New Zealand case reports

Up to 30 June 2021, the Centre for Adverse Reactions Monitoring (CARM) had received 70 reports of congenital malformation or neurodevelopmental adverse effects associated with exposure to one or more medicines during pregnancy. In recent years, most of these reports have been for fetal valproate syndrome or autism associated with sodium valproate exposure during pregnancy.

References

1. Dathe K and Schaefer C. 2019. The use of medication in pregnancy. Deutsches Ārzteblatt International 116(46): 783–90. DOI: 10.3238/arztebl.2019.0783 (accessed 19 October 2021).
2. Daw JR, Hanley GE, Greyson DL, et al. 2011. Prescription drug use during pregnancy in developed countries: A systematic review. Pharmacoepidemiology and Drug Safety 20(9): 895–902. DOI: https://doi.org/10.1002/pds.2184 (accessed 19 October 2021).
3. Donald S, Sharples K, Barson D, et al. 2020. Patterns of prescription medicine dispensing before and during pregnancy in New Zealand, 2005–2015. PLOS ONE 15(6): e0234153. DOI: 10.1371/journal.pone.0234153 (accessed 19 October 2021).
4. El Shamy T and Tamizian O. 2021. Principles of prescribing in pregnancy. Obstetrics, Gynaecology & Reproductive Medicine 31(11): 317–22. DOI: https://www.sciencedirect.com/science/article/pii/S1751721421001664 (accessed 21 October 2021).
5. Hohmann-Marriott BE. 2018. Unplanned pregnancies in New Zealand. Australian and New Zealand Journal of Obstetrics and Gynaecology 58(2): 247–50. DOI: 10.1111/ajo.12732 (accessed 20 October 2021).
6. Douglas Pharmaceuticals Ltd. NZ. 2019. Oratane New Zealand Data Sheet 29 October 2019. URL: medsafe.govt.nz/profs/Datasheet/o/oratanecap.pdf (accessed 20 October 2021).
7. Douglas Pharmaceuticals Ltd NZ. 2021. Novatretin New Zealand Data Sheet 31 August 2021. URL: medsafe.govt.nz/profs/Datasheet/n/novatretincap.pdf (accessed 20 October 2021).
8. Medsafe. 2020. Acitretin: Changes to pregnancy prevention requirements. Prescriber Update 41(1): 7–8. URL: medsafe.govt.nz/profs/PUArticles/March2020/Acitretin-pregnancy-prevention-requirements.html (accessed 20 October 2021).
9. Johansen-Bibby A. 2020. Prescribing for pregnancy: Epilepsy. Drug and Therapeutics Bulletin 58(7): 103. DOI: 10.1136/dtb.2019.000009 (accessed 21 October 2021).
10. Sanofi-Aventis New Zealand Limited. 2021. Epilim New Zealand Data Sheet 3 May 2021. URL: medsafe.govt.nz/profs/Datasheet/e/Epilimtabsyrliqiv.pdf (accessed 20 October 2021).
11. Medsafe. 2019. Alert Communication: Use of sodium valproate (Epilim) in girls and women - Change to indications and contraindications. 4 March 2019. URL: www.medsafe.govt.nz/safety/Alerts/Epilim.asp (accessed 22 October 2021).
12. New Zealand Formulary (NZF). 2021. NZF v113: Control of the epilepsies – Pregnancy 1 November 2021. URL: nzf.org.nz/nzf_2600#nzf_2605 (accessed 4 November 2021).
13. Celgene Ltd. 2019. Revlimid New Zealand Data Sheet 27 September 2019. URL: medsafe.govt.nz/profs/Datasheet/r/revlimidcap.pdf (accessed 20 October 2021).
14. BPAC NZ. 2021. Oral contraceptives: Selecting a pill 20 July 2021. URL: bpac.org.nz/2021/contraception/oral-contraceptives.aspx (accessed 20 October 2021).