The UK MHRA Update on Epilim-Valproate

The UK MHRA Regulatory Guidance on the Epilim – Valproate Pregnancy Prevention Program (PREVENT)

Temporary advice for management during coronavirus (COVID-19) pandemic.

OACS Ireland welcomes the UK regulators the MHRA guidance for specialists for initiation of valproate in female patients and for annual review and pregnancy testing to support adherence to pregnancy prevention requirements during the pandemic. Additionally, the MHRA has sought advice from expert advisors, including healthcare professionals managing patients on valproate. Which incorporates patient representatives affected by the harms of valproate in pregnancy in UK and Ireland. The MHRA issued the following temporary advice to ensure the Pregnancy Prevention Program (PPP) requirements can be met safely in this current climate. See link to the guidance due to Covid-19 pandemic via the MHRA website.

OACS Ireland has asked the HPRA to incorporate the same guidance in Ireland with regard to Covid-19 at a regulatory level . As, Karen Keely Chairperson of OACS Ireland stated at the EMA review in 2017 in relation to Epilim – (Valproate) in Ireland “ticking a box is never enough”. It is now well known there is no safe dose of Epilim (valproate) that can be used in pregnancy ensuring the protection of the unborn must take precedence above all else.Link to the HPRA website page www.hpra.ie/.

References:

1. Weston J, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev. 2016 Nov 7;11: CD010224. 
2. Thompson, et al. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurol 2018; 17: 530–38. 
3. Bromley RL, et al. [Early cognitive development in children born to women with epilepsy: a prospective report]https://doi.org/10.1111/j.1528-1167.2010.02668.x). Epilepsia 2010; 51: 2058–65. 
4. Meador KJ, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol 2013 12: 244–52. 
5. Christensen J et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 2013; 309: 1696–703. 
6. Cohen MJ et al. Fetal antiepileptic drug exposure: motor, adaptive and emotional/ behavioural functioning at age 3 years. Epilepsy Behav 2011; 22: 240–246. 

Associated names: In relation to Epilim – Sodium Valproate throughout Europe.         

Valproate and related substances international non-proprietary name (INN) or common name of sodium valproate, valproate magnesium, valproate semisodium, valproic acid, valpromide. Which are marketed under several brand names including: Absenor, Convival Chrono, Convulex, Convulsofin,Tabletten, Delepsine, Depakine, Deprakine, Diplexil, Dipromal, Episenta, Epival, Ergenyl, Espa-Valept, Hexaquin, Leptilan, Micropakine L.P., Orfiril, Orlept, Petilin, Valberg, Valepil and Valhel

The MHRA is Monitoring impact of Epilim Sodium Valproate see the data.

The MHRA has been monitoring trends in the prescribing of sodium valproate to assess the impact of evolving regulatory recommendations and introduction of the pregnancy prevention programme using primary care data from the Clinical Practice Research Datalink GOLD database. 

Version 4 – CPRD study monitoring the use of valproate in girls and women in the UK: report from January 2010 to December 2019 (PDF, 277KB, 8 pages)

Version 3 – CPRD study monitoring the use of valproate in girls and women in the UK: report from January 2010 to  (PDF, 243KB, 5 pages)

Version 2 – CPRD study monitoring the use of valproate in girls and women in the UK – report from January 2010 to December 2018 (PDF, 200KB, 5 pages)

Version 1 – CPRD study monitoring the use of valproate in girls and women in the UK – report from January 2010 to June 2018 (PDF, 145KB, 4 pages)

The MHRA will continue to monitor these and other data sources, including clinical audits and patient surveys, and will take action as necessary to protect public health.

Please do Not Stop taking your medication without speaking to your Health Care Professional

Stay Safe

OACS Ireland