Pharmaceutical Benefits Scheme restrictions on anti‐epileptic drug prescribing promote unsafe and outdated practice

Christian A Gericke and Terence J O'Brien
Med J Aust 2019; 211 (2): . || doi: 10.5694/mja2.50246
Published online: 1 July 2019

The PBS urgently needs to update anti‐epileptic drug prescribing restrictions that put patients and prescribers at risk

In May 2018, the European Medicines Agency banned the prescription of valproate to women of childbearing age for use in migraine and bipolar disorder unless they are enrolled in a special pregnancy prevention program. Its use in epilepsy is banned unless there is no other effective treatment available.1 This follows numerous reports of a substantially increased, dose‐related risk of fetal malformations (in particular neural tube defects including spina bifida) in babies born to mothers exposed to valproate during pregnancy.2,3 In addition, newer longitudinal studies showed a substantial negative effect on multiple cognitive domains in children exposed to valproate in utero.4 On average, their intelligence quotient at 6 years of age is reduced by 7 to 10 points compared with children exposed to other anti‐epileptic drugs (AEDs).4 Manufacturers and national pharmaceutical regulators first warned of the risk of severe congenital malformations in the 1990s and, in practice, most epileptologists worldwide have avoided prescribing valproate to pregnant women ever since.5 This was made possible by the licensing of two new drugs that are highly effective in genetic generalised epilepsies but without the risk of neural tube defects or likely neurocognitive effects: lamotrigine (first licensed in 1994) and levetiracetam (first licensed in 1999). To avoid common adverse effects of valproate, such as weight gain, metabolic syndrome, hair loss and gastrointestinal disturbance, epileptologists have since also reduced prescribing valproate to women without childbearing potential and to men. The only exception most epileptologists would accept for prescribing valproate during pregnancy is in women with genetic generalised epilepsy in whom seizure control is not achieved with levetiracetam, lamotrigine or topiramate, often in combination therapy. Usually, such women do respond to small doses of valproate in combination with lamotrigine or levetiracetam. As the valproate‐induced fetal malformations are dose‐dependent, the risk of fetal malformations is balanced with the risk of uncontrolled generalised tonic–clonic seizures during pregnancy.

  • 1 University of Queensland and The Prince Charles Hospital, Brisbane, QLD
  • 2 The Alfred Hospital and Monash University, Melbourne, VIC


Competing interests:

Christian Gericke is Specialist Advisor to the Therapeutic Goods Administration. He has received sponsorship from Eisai and UCB to attend educational events and his institution has received research funding from UCB. Terence O'Brien is President of the Epilepsy Society of Australia. His institution has received research grants and consulting fees from manufacturers of AEDs, including UCB, Eisai, Sanofi and Zynerba Pharmaceuticals.


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