The government is now operating in accordance with the Guidance on Caretaker Conventions, pending the outcome of the 2025 federal election.
Summary
The Product Information (PI) for pregabalin - external site has been updated to strengthen the warning to avoid prescribing in pregnancy. The change was made after a study showed an increased risk of major congenital malformations associated with the medicine.
Pregabalin is an antiepileptic medicine used for the treatment of neuropathic pain and as an adjunctive therapy for partial seizures.
Women should use effective contraception if they are taking pregabalin and treatment should not be prescribed to pregnant women unless the benefits to the mother clearly outweigh the potential risks to their unborn child.
What’s new in this article
The strengthened warning follows recent data from a Nordic observational study of more than 2,700 pregnant women exposed to pregabalin in the first trimester. The study used data from national registries in Denmark, Finland, Norway and Sweden and compared babies born to mothers who took pregabalin, lamotrigine, duloxetine or none of these medicines. The study found a higher prevalence of major congenital malformations among babies exposed to pregabalin in utero compared to babies who were not exposed (5.9% vs. 4.1%).[1]
In response to these findings, the pregnancy category for pregabalin has been changed from B3 to D in Australia. The PI for the innovator pregabalin product, Lyrica, has been updated to include additional warnings and a summary of the results from the Nordic study. Generic sponsors of pregabalin will update their PIs to align with this safety information.
What should health professionals do
Health professionals should inform women using pregabalin about the potential risks to an unborn baby and advise them to use effective contraception during treatment.
Pregabalin should only be prescribed during pregnancy if the benefit to the patient clearly outweighs the potential risk to the fetus - the patient should understand the benefits and risks of pregabalin and be aware of alternatives, and be part of the decision-making process.
Background
Previously, the Therapeutic Goods Administration (TGA) evaluated the safety of epilepsy medicines during pregnancy following a review in the UK.[2] As a result, the TGA updated precautions for the use of phenytoin, phenobarbital, primidone and zonisamide in pregnancy.[3]
At that time, no firm conclusions could be drawn on the possible teratogenic effects of pregabalin in the UK study and the TGA’s Advisory Committee on Medicines found the PI for pregabalin adequately described the risks in pregnancy and did not need updating.[4]
PI changes for Lyrica
The pregnancy category for pregabalin has been changed from B3 to D.
Section 4.4 now includes a special warning for women of childbearing age which states:
‘Lyrica use in the first trimester of pregnancy may cause major birth defects in the unborn child. Pregabalin should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the fetus. Women of childbearing potential have to use effective contraception during treatment.’
Section 4.6 now includes a summary of the Nordic observational study:
‘Data from a Nordic observational study of more than 2,700 pregnancies exposed to pregabalin in the first trimester showed a higher prevalence of major congenital malformations (MCM) among the paediatric population (live or stillborn) exposed to pregabalin compared to the unexposed population (5.9% vs. 4.1%).
‘The risk of MCM among the paediatric population exposed to pregabalin in the first trimester was slightly higher compared to unexposed population (adjusted prevalence ratio and 95% confidence interval: 1.14 (0.96-1.35)), and compared to population exposed to lamotrigine (1.29 (1.01–1.65)) or to duloxetine (1.39 (1.07–1.82)).
‘The analyses on specific malformations showed higher risks for malformations of the nervous system, the eye, orofacial clefts, urinary malformations and genital malformations, but numbers were small and estimates imprecise.’
Reference
| [1] | Wise J. Avoid prescribing pregabalin during pregnancy if possible, says UK drug regulator - external site. BMJ 2022;377:o1010 doi: https://doi.org/10.1136/bmj.o1010 - external site (Published 21 April 2022). |
|---|---|
| [2] | Medicines and Healthcare products Regulatory Agency. Antiepileptic drugs: review of safety of use in pregnancy. - external site 2021. |
| [3] | Antiepileptic medicines – updated precautions for pregnancy and women of childbearing potential. Medicines Safety Update 22 June 2022. |
| [4] | Therapeutic Goods Administration. Advisory Committee on Medicines meeting statement. 2021. |
What to report? You don't need to be certain, just suspicious!
The TGA encourages the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, herbal, traditional or alternative remedies.
We particularly request reports of:
- all suspected reactions to new medicines (look for the Black Triangle ▼ in PI and CMI documents – this symbol identifies medicines that are new or being used differently)
- all suspected medicines interactions
- suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.
To report a suspected side effect or for more information about reporting, go to our ‘Report problem or side effect’ webpage or contact the TGA's Pharmacovigilance Branch ADR.Reports@health.gov.au.
Disclaimer
Medicines Safety Update is aimed at health professionals. It is intended to provide practical information to health professionals on medicine safety, including emerging safety issues. The information in Medicines Safety Update is necessarily general and is not intended to be a substitute for a health professional's judgment in each case, taking into account the individual circumstances of their patients. Reasonable care has been taken to ensure that the information is accurate and complete at the time of publication. The Australian Government gives no warranty that the information in this document is accurate or complete, and shall not be liable for any loss whatsoever due to negligence or otherwise arising from the use of or reliance on this document.
© Commonwealth of Australia 2022
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For correspondence or further information about Medicines Safety Update, contact the TGA's Pharmacovigilance Branch at ADR.Reports@health.gov.au.
Medicines Safety Update is written by staff from the Pharmacovigilance Branch.
Editor: Elspeth Kay
Deputy Editor: Fiona Mackinnon
Contributors: Leanne Nelson, Kat Chen