Safety Information

Alert Communication

Use of sodium valproate (Epilim) in girls and women – Change to indications and contraindications

4 March 2019

Taking sodium valproate (Epilim) in pregnancy has a high risk of birth defects and developmental problems for the baby. For this reason the indication for use in bipolar disorder has changed. Sodium valproate may now only be used in women of childbearing potential when all other treatments are ineffective or not tolerated. In addition women must use effective contraception while taking sodium valproate.

The sodium valproate patient information booklet and guide for healthcare professionals have been updated by the company to support these changes.

Sodium valproate must not be used in the following situations due to risks to the unborn baby:

Girls or women of childbearing potential unless other treatments are ineffective or not tolerated.
During pregnancy for the treatment of epilepsy unless there is no suitable alternative treatment.
During pregnancy for the treatment of bipolar disorder.

In addition, sodium valproate must not be used for unapproved indications in women of childbearing potential.

It is important that girls (and their parents/caregivers) and women of childbearing potential taking sodium valproate for any indication are aware of and understand the risks. See the ‘Detailed information’ section below for a description of the level of risk.

Treatment with sodium valproate in girls and women of childbearing potential must be initiated and supervised by a specialist.

No woman or girl should stop taking sodium valproate without first discussing it with their doctor.

Advice for girls (and their parents/caregivers) and women

Sodium valproate can seriously harm an unborn baby when taken during pregnancy.
Make sure you understand the risks to an unborn baby when taking sodium valproate. Ask your doctor if there is something you don’t understand.
Your doctor may prescribe sodium valproate because other treatments either do not control your condition or you can’t tolerate them. Your doctor will discuss this with you and explain the benefits and risks of using sodium valproate.
If you are old enough to become pregnant, your doctor will ask you to do a pregnancy test before starting treatment with sodium valproate and during treatment as needed. This is to make sure you are not pregnant.
Always use effective contraception when taking sodium valproate to prevent unplanned pregnancy if you are old enough to become pregnant. Use contraception for the whole time you are taking sodium valproate and do not stop using contraception at any time while taking sodium valproate.
Contact your doctor immediately if you think you may be pregnant. Do not stop taking sodium valproate until you have discussed this with your doctor as there are risks to yourself and your unborn child from uncontrolled epilepsy or uncontrolled mania episodes.
Contact your doctor promptly if you are thinking about having a baby. You will need plenty of time to discuss and decide on the best option for you, which may include changing treatment. Do not stop using contraception until you have talked to your doctor.
Do not stop taking sodium valproate unless your doctor tells you to.
Remember to visit your specialist regularly (ideally at least once a year).

Information for prescribers

Prescribing sodium valproate for girls, women of childbearing potential and pregnant women:

Treatment with sodium valproate must be initiated and supervised by a specialist.
Do not prescribe sodium valproate for the treatment of epilepsy in pregnant women unless there is no suitable alternative treatment.
Do not prescribe sodium valproate for the treatment of bipolar disorder, or any other condition in pregnant women.
Involve patients in discussions and check that they understand the risks and measures needed to minimise the risks. The patient should verbally acknowledge and you should suitably document that she has understood the risks and necessary precautions.

Additional considerations for women of childbearing potential:

Evaluate and discuss the benefits and risks of treatment with sodium valproate with each patient before use. Discuss the risks to pregnancy associated with the underlying condition.
Discuss risks to the fetus of exposure to sodium valproate in pregnancy. These risks include congenital malformations (eg, spina bifida, cleft palate, heart defects) and neurodevelopmental disorders (eg, developmental delay, learning problems, lower IQ, autistic spectrum disorders or autism). See ‘Detailed information’ section below.
Discuss the need to use effective contraception throughout treatment without interruption. At least one effective method that is user-independent (eg, intrauterine device or implant), or two complementary methods including a barrier method should be used.
Discuss the need for a blood pregnancy test prior to starting treatment and during treatment, as needed, to exclude pregnancy.
Specialists experienced in the management of epilepsy or bipolar disorder should regularly review treatment (ideally at least once a year).
Inform patients not to stop treatment with sodium valproate and to contact their doctor immediately in case of planned or suspected pregnancy.
Inform patients they can access a patient guide electronically using the QR code on the Epilim box. There is also a patient information booklet on taking medicines for epilepsy, mood or pain from ACC (see ‘Useful links’ section below for access to all of these resources).

Additional considerations for girls:

Ensure parents/caregivers understand the need to contact the specialist once their female child using sodium valproate reaches menarche.
Ensure parents/caregivers of female children who have reached menarche are provided with good information on the risks to a baby of congenital malformations and neurodevelopmental disorders, including the size of these risks. See ‘Detailed information’ section below.
Specialists must reassess the need for sodium valproate treatment and consider alternative treatment options for patients who have reached menarche. If sodium valproate is the only suitable treatment, the need for using effective contraception should be discussed.

Information for pharmacists

Dispense sodium valproate (Epilim) in the original packaging where possible, especially for girls and women of childbearing potential. This is important because it has a manufacturer’s warning for women and girls.
Check that your patients are able to access the sodium valproate patient information booklet using the QR code on the Epilim box. Review the patient information booklet with them.
Ensure patients have a copy of ACC’s booklet on taking medicines for epilepsy, mood or pain (see ‘Useful links’ section below).
Reinforce the need to use effective contraception throughout treatment without interruption.
Remind girls and women of childbearing potential not to stop treatment with sodium valproate and to immediately contact their doctor in case of planned or suspected pregnancy.

Detailed information

The use of sodium valproate in pregnancy for epilepsy and bipolar disorder (the approved indications) was discussed by the Medicines Adverse Reactions Committee (MARC) in September 2017. The committee recommended a change to the bipolar indication.

Sodium valproate is associated with a high risk of birth defects and developmental problems in children whose mothers take sodium valproate during pregnancy.

The risks are higher with sodium valproate than with other medicines for epilepsy or bipolar disorder.
The risks are present even with low doses of sodium valproate and increase with higher doses.

These risks are as follows.

Birth defects (congenital malformations)
Birth defects with sodium valproate include:
- spina bifida (where the bones and membranes around the spine do not develop properly)
- face and skull malformations (including cleft palate)
- malformations of the limbs, heart, kidney, urinary tract and sexual organs.
How big is the risk?
- About 10 out of 100 babies exposed to sodium valproate will have a birth defect.
- By comparison, 2 to 3 out of 100 babies not exposed to antiepileptic medicines will have a birth defect.
The risk seems to be dose-dependent and increases with higher doses (above 1000 mg daily). A threshold dose below which no risk exists cannot be established based on available data.
Learning and behavioural problems (neurodevelopmental disorders)
Effects on development include:
- delay in learning to walk and talk
- lower IQ than other children of the same age
- poor speech and language skills
- memory problems.
How big is the risk?
- Up to 40 out of 100 children may have problems with development.
Children of mothers who take sodium valproate during pregnancy are more likely to have autism or autistic spectrum disorders. Limited data suggests that children exposed in utero may be more likely to have signs of attention deficit hyperactivity disorder (ADHD).

The exact gestational period of risk for these effects is not known. The possibility of a risk from exposure to sodium valproate at any stage during pregnancy cannot be excluded.

Useful links

Girls (and their parents/caregivers) and women:

Healthcare professionals:

MEDSAFE

New Zealand Medicines and Medical Devices Safety Authority