Epilim®

Epilim® (sodium valproate) for the treatment of patients with Epilepsy and Bipolar Mood Disorder

Epilim (Sodium Valproate): Annual Reminder on Restrictions of Use

This is a reminder on the important safety information with regards to the use of Epilim (Sodium Valproate), this includes the contraindications, strengthened warnings and measures to prevent valproate exposure during pregnancy.

Summary

  • Valproate should not be used in female children and women of childbearing potential unless other treatments are ineffective or not tolerated.
  • Children exposed in utero to valproate are at a high risk of serious developmental disorders (in up to 30-40% of cases) and of congenital malformations (in approximately 10% of cases).
  • In pregnancy and in women of childbearing potential new contraindications apply:
    • In epilepsy
      • valproate is contraindicated in pregnancy unless there is no suitable alternative treatment.
      • valproate is contraindicated in women of childbearing potential, unless the conditions described below are fulfilled.
    • In bipolar disorder
      •  valproate is contraindicated in pregnancy.
      • valproate is contraindicated in women of childbearing potential, unless the conditions described below are fulfilled.


In girls and women of childbearing potential currently using valproate, management will need to be reevaluated to ensure that the conditions described below are met:

The prescriber must ensure that:

  • individual circumstances should be evaluated in each case, involving the patient in the discussion, to guarantee her engagement, discuss therapeutic options and ensure her understanding of the risks and the measures needed to minimise the risks.
  •  the potential for pregnancy is assessed for all female patients.
  •  the patient has understood and acknowledged the risks of congenital malformations and neurodevelopmental disorders, including the magnitude of these risks for children exposed to valproate in utero.
  •  the patient understands the need to undergo pregnancy testing prior to initiation of treatment and during treatment, as needed.
  •  the patient is counselled regarding contraception, and that the patient is capable of complying with the need to use effective contraception, without interruption during the entire duration of treatment with valproate.
  • the patient understands the need for regular (at least annual) review of treatment by a specialist experienced in the management of epilepsy or bipolar disorders.
  •  the patient understands the need to consult her physician as soon as she is planning a pregnancy to ensure timely discussion and switching to alternative treatment prior to conception, and before contraception is discontinued.
  •  the patient understands the need to urgently consult her physician in case of pregnancy.
  •  the patient has received the patient guide.
  •  the patient has acknowledged that she has understood the hazards and necessary precautions associated with valproate use (Annual Risk Acknowledgement Form).

These conditions also concern women who are not sexually active unless the prescriber considers that there are compelling reasons to indicate that there is no risk of pregnancy.

The communication of this information has been agreed with the National Centre for Adverse Drug Reaction Monitoring, National Pharmaceutical Regulatory Agency (NPRA) [formerly known as National Pharmaceutical Control Bureau (NPCB)], Ministry of Health Malaysia.

Educational materials

In order to assist healthcare professionals and patients in avoiding exposure to valproate during pregnancy, a Patient Card, a Patient Guide, an annual risk acknowledgment form, and a Guide for prescribers, pharmacists and other healthcare providers involved in the care of women of childbearing potential using valproate will be available to inform healthcare professionals and patients/caregivers on the risks of valproate and the conditions for use.

A patient guide and patient card should be provided to all women of childbearing potential using valproate. An annual risk acknowledgement form needs to be used by the specialists at time of treatment initiation and during each annual review of valproate treatment by the specialist.

English Version

• Cover Letter

• Healthcare Professional Guide

• Patient Guide

• Patient Card

• Annual Risk Assessment Form

Versi Bahasa Melayu

• Borang Perakuan Risiko Tahunan

• Panduan Pesakit

• Kad Pesakit

 

Background information

In 2015 the warnings and restrictions on the use of valproate medicines in women and girls were strengthened, to minimize the risk of malformations and developmental problems in babies exposed to valproate in the womb.

Risk of abnormal pregnancy outcomes

Valproate is associated with a dose-dependent risk of abnormal pregnancy outcomes, whether taken alone or in combination with other medicines. Data suggest that when valproate is taken for epilepsy with other medicines, the risk of abnormal pregnancy outcomes is greater than when valproate is taken alone.

  • The risk of congenital malformations is approximately 10%, while studies in preschool children exposed in utero to valproate show that in up to 30-40%, early development such as talking, and walking is delayed and they have low intellectual abilities, poor language skills and memory problems.1,2,3,4,5
  • Intelligence quotient (IQ) measured in a study of 6-year-old children with a history of valproate exposure in utero was on average 7-10 points lower than children exposed to other antiepileptics.6
  • Available data show that children exposed to valproate in utero are at increased risk of autistic spectrum disorder (approximately three-fold) and childhood autism (approximately five-fold) compared with the general study population.7
  • Limited data suggest that children exposed to valproate in utero may be more likely to develop symptoms of attention deficit/hyperactivity disorder (ADHD).8

Status for product information

The product information of all valproate-containing products has been updated accordingly.

Call for reporting

Any suspected adverse events should be reported to National Centre for Adverse Drug Reaction Monitoring, NPRA:

Company contact point

Adverse drug reactions should also be reported to sanofi-aventis (Malaysia) Sdn Bhd, pharmacovigilance mailbox pv-malaysia@sanofi.com

For further medical information on Epilim®, please contact sanofi-aventis (Malaysia) Sdn Bhd medical enquiry mailbox Med.SAMS@sanofi.com with the subject title “EPILIM”.

    1. Weston J, Bromley R, Jackson CF, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database of Systematic Reviews 2016, Issue 11. Art. No.: CD010224.
    2. Bromley RL, et al. Early cognitive development in children born to women with epilepsy: a prospective report. Epilepsia 2010 October; 51(10):205865.
    3. Cummings C et al. Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine. Arch Dis Child 2011;96: 643647.
    4. Meador K et al. Cognitive Function at 3 years of age after fetal exposure to antiepileptic drugs. NEJM 2009;360(16):15971605.
    5. Thomas SV et al. Motor and mental development of infants exposed to antiepileptic drugs in utero. Epilepsy and Behaviour 2008 (13):229236.
    6. Meador KJ, et al. NEAD Study Group. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol 2013;12(3):244-52.
    7. Christensen J et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 2013;309(16):16961703.
    8. Cohen MJ et al. Fetal antiepileptic drug exposure: motor, adaptive and emotional/behavioural functioning at age 3 years. Epilepsy Behav. 2011; 22(2):240246.