Episenta, sodium valproate can seriously harm an unborn child when taken during pregnancy. If you are a female able to have a baby you must use effective method of birth control (contraception) without interruptions during your entire treatment with Episenta. Your doctor will discuss this with you but you must also follow the advice in section 2 of this leaflet.

Schedule an urgent appointment with your doctor if you want to become pregnant or if you think you are pregnant.

Do not stop taking Episenta unless your doctor tells you to as your condition may become worse.

If you are a parent or caregiver of a female child treated with Episenta, you must also read section 2 of this leaflet carefully and contact your child’s doctor once they experience their first period (menarche).

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms seem the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Episenta is and what it is used for
2. What you need to know before you take Episenta
3. How to take Episenta
4. Possible side effects
5. How to store Episenta
6. Contents of the pack and other information

• if you are allergic to sodium valproate or any of the other ingredients of this medicine (listed in section 6)
• if you, or a member of your family, have or have had severe liver problems
• if you suffer from a disease called porphyria (a rare condition that affects the breakdown of components of red blood cells)
• if you have a genetic problem causing a mitochondrial disorder (e.g. Alpers-Huttenlocher syndrome)
• if you suffer from urea cycle disorder (a certain metabolic disorder)

Bipolar disorder

• For bipolar disorder, you must not use Episenta if you are pregnant.
• For bipolar disorder, if you are a woman able to have a baby, you must not take Episenta, unless you use effective method of birth control (contraception) during your entire treatment with Episenta. Do not stop taking Episenta or your contraception, until you have discussed this with your doctor. Your doctor will advise you further (see below under “Pregnancy, breast-feeding and fertility – Important advice for women”).

Epilepsy

• For epilepsy, you must not use Episenta if you are pregnant, unless nothing else works for you.
• For epilepsy, if you are a woman able to have a baby, you must not take Episenta unless you use effective method of birth control (contraception) during your entire treatment with Episenta. Do not stop taking Episenta or your contraception, until you have discussed this with your doctor. Your doctor will advise you further (see below under “Pregnancy, breast-feeding and fertility – Important advice for women”).

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Episenta.

A small number of people being treated with antiepileptics such as sodium valproate have had thoughts of harming or killing themselves. If at any time you have these thoughts, immediately contact your doctor.

As with other antiepileptic drugs, convulsions may become worse or happen more frequently whilst taking this medicine. If this happens contact your doctor immediately.

Talk to your doctor or pharmacist before taking Episenta if:

• you have diabetes. This medicine may affect the results of urine tests.
• you have a carnitine palmitoyltransferase type II deficiency.
• you have kidney problems. Your doctor may give you a lower dose.
• you have a brain disease or a metabolic condition affecting your brain.
• you have a ‘urea cycle disorder’ where too much ammonia builds up in the body.
• you have an illness called ‘systemic lupus erythematosus (SLE)’ – a disease of the immune system which affects skin, bones, joints and internal organs.
• you know that there is a genetic problem caused by a mitochondrial disorder in your family.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Episenta.

Taking Episenta may make you put on weight. Talk to your doctor about how this will affect you.

Your doctor may wish to do blood tests before you start taking Episenta and during your treatment.

Children and adolescents under 18 years of age: Episenta should not be used in children and adolescents under 18 years of age for the treatment of mania.

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Episenta can affect the way some other medicines work. Also some medicines can affect the way Episenta works.

The following medicines can increase the chance of you getting side effects, when taken with Episenta:

• some medicines used for pain and inflammation (salicylates) such as aspirin
• some other medicines used to treat fits (epilepsy) – see section 3, ‘Patients taking other medicines for fits’. This includes medicines such as phenobarbital, primidone, phenytoin, carbamazepine, rufinamide, topiramate, lamotrigine and felbamate.
• acetazolamide used to treat glaucoma, edema or fits

Episenta may increase the effect of the following medicines:

• medicines used for thinning the blood (such as warfarin)
• zidovudine used to treat HIV infection
• temozolomide used to treat cancer
• medicines for depression
• monoamine oxidase inhibitors (MAOI) such as moclobemide, selegiline, linezolid
• medicines used to calm emotional and mental health problems (including schizophrenia, bipolar disorder and depression) such as quetiapine, diazepam and olanzapine
• nimodipine
• propofol – used for anaesthesia

The following medicines can affect the way Episenta works:

• oestrogen-containing products (including some birth control pills)
• some medicines used for the prevention and treatment of malaria such as mefloquine and chloroquine
• cimetidine used for stomach ulcers
• protease inhibitors such as lopinavir and ritonavir – used for HIV infection and AIDS
• antibiotics e.g. erythromycin, carbapenem agents (antibiotics used to treat bacterial infections). The combination of valproic acid and carbapenems should be avoided because it may decrease the effect of sodium valproate.
• rifampicin used to treat tuberculosis and other infections
• cholestyramine used to lower blood fat (cholesterol) levels
• metamizole, a medicine used to treat pain and fever

It may still be possible for you to take Episenta; your doctor will advise you on what is suitable for you.

Alcohol intake is not recommended during treatment.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Bipolar disorder

• For bipolar disorder, you must not use Episenta if you are pregnant.
• For bipolar disorder, if you are a woman able to have a baby, you must not take Episenta, unless you use effective method of birth control (contraception) during your entire treatment with Episenta. Do not stop taking Episenta or your contraception, until you have discussed this with your doctor. Your doctor will advise you further.

Epilepsy

• For epilepsy, you must not use Episenta if you are pregnant, unless nothing else works for you.
• For epilepsy, if you are a woman able to have a baby, you must not take Episenta unless you use effective method of birth control (contraception) during your entire treatment with Episenta. Do not stop taking Episenta or your contraception, until you have discussed this with your doctor. Your doctor will advise you further.

The risks of valproate when taken during pregnancy

(irrespective of the disease for which valproate is used)

• Talk to your doctor immediately if you are planning to have a baby or are pregnant.
• Valproate carries a risk if taken during pregnancy. The higher the dose, the higher the risks but all doses carry a risk.
• It can cause serious birth defects and can affect the way in which the child develops as it grows. The most frequently reported birth defects include spina bifida (where the bones of the spine are not properly developed); facial and skull malformations; heart, kidney, urinary tract and sexual organ malformations; limb defects and multiple associated malformations affecting several organs and parts of the body. Birth defects may result in disabilities which may be severe.
• Hearing problems or deafness have been reported in children exposed to valproate during pregnancy.
• Eye malformations have been reported in children exposed to valproate during pregnancy in association with other congenital malformations. These eye malformations may affect vision.
• If you take valproate during pregnancy you have a higher risk than other women of having a child with birth defects that require medical treatment. Because valproate has been used for many years we know that in women who take valproate around 10 babies in every 100 will have birth defects. This compares to 2 to 3 babies in every 100 born to women who don’t have epilepsy.
• It is estimated that up to 30 – 40% of preschool children whose mothers took valproate during pregnancy may have problems with early childhood development. Children affected can be slow to walk and talk, intellectually less able than other children, and have difficulty with language and memory.
• Autistic spectrum disorders are more often diagnosed in children exposed to valproate during pregnancy, and there is some evidence that children exposed to valproate during pregnancy are at increased risk of developing Attention Deficit Hyperactivity Disorder (ADHD).
• Before prescribing this medicine to you, your doctor will have explained what might happen to your baby if you become pregnant whilst taking valproate. If you decide later you want to have a baby you must not stop taking your medicine or your method of contraception until you have discussed this with your doctor.
• If you are a parent or a caregiver of a female child treated with valproate, you should contact the doctor once your child using valproate experiences their first period (menarche).
• Ask your doctor about taking folic acid when trying for a baby. Folic acid can lower the general risk of spina bifida and early miscarriage that exists with all pregnancies. However, it is unlikely that it will reduce the risk of birth defects associated with valproate use.

• I AM STARTING TREATMENT WITH EPISENTA
• I AM TAKING EPISENTA AND NOT PLANNING TO HAVE A BABY
• I AM TAKING EPISENTA AND PLANNING TO HAVE A BABY
• I AM PREGNANT AND I AM TAKING EPISENTA

If this is the first time you have been prescribed Episenta your doctor will have explained the risks to an unborn child if you become pregnant. Once you are able to have a baby, you will need to make sure you use an effective method of contraception without interruption throughout your treatment with Episenta. Talk to your doctor or family planning clinic if you need advice on contraception.

Key messages:

• Pregnancy must be excluded before start of treatment with Episenta with the result of a pregnancy test, confirmed by your doctor.
• You must use an effective method of birth control (contraception) during your entire treatment with Episenta.
• You must discuss the appropriate methods of birth control (contraception) with your doctor. Your doctor will give you information on preventing pregnancy, and may refer you to a specialist for advice on birth control.
• Some birth control pills (oestrogen-containing birth control pills) may lower valproate levels in your blood. Make sure you talk to your doctor about the method of birth control (contraception) that is the most appropriate for you.
• You must get regular (at least annual) appointments with a specialist experienced in the management of bipolar disorder or epilepsy. During this visit your doctor will make sure you are well aware and have understood all the risks and advices related to the use of valproate during pregnancy.
• Tell your doctor if you want to have a baby.
• Tell your doctor immediately if you are pregnant or think you might be pregnant.

If you are continuing treatment with Episenta but you are not planning to have a baby make sure you are using an effective method of contraception without interruption during your entire treatment with Episenta. Talk to your doctor or family planning clinic if you need advice on contraception.

Key messages:

• You must use an effective method of birth control (contraception) during your entire treatment with Episenta.
• You must discuss contraception (birth control) with your doctor. Your doctor will give you information on preventing pregnancy, and may refer you to a specialist for advice on birth control.
• Some birth control pills (oestrogen-containing birth control pills) may lower valproate levels in your blood. Make sure you talk to your doctor about the method of birth control (contraception) that is the most appropriate for you.
• You must get regular (at least annual) appointments with a specialist experienced in the management of bipolar disorder or epilepsy. During this visit your doctor will make sure you are well aware and have understood all the risks and advices related to the use of valproate during pregnancy.
• Tell your doctor if you want to have a baby.
• Tell your doctor immediately if you are pregnant or think you might be pregnant.

If you are planning to have a baby, first schedule an appointment with your doctor.

Do not stop taking Episenta or your contraception, until you have discussed this with your doctor. Your doctor will advise you further.

Babies born to mothers who have been on valproate are at serious risk of birth defects and problems with development which can be seriously debilitating. Your doctor will refer you to a specialist experienced in the management of bipolar disorder or epilepsy, so that alternative treatment options can be evaluated early on. Your specialist can put several actions in place so that your pregnancy goes as smoothly as possible and any risks to you and your unborn child are reduced as much as possible.

Your specialist may decide to change the dose of Episenta or switch you to another medicine, or stop treatment with Episenta, a long time before you become pregnant – this is to make sure your illness is stable.

Ask your doctor about taking folic acid when planning to have a baby. Folic acid can lower the general risk of spina bifida and early miscarriage that exists with all pregnancies. However, it is unlikely that it will reduce the risk of birth defects associated with valproate use.

Key messages:

• Do not stop taking Episenta unless your doctor tells you to.
• Do not stop using your methods of birth control (contraception) before you have talked to your doctor and worked together on a plan to ensure your condition is controlled and the risks to your baby are reduced.
• First schedule an appointment with your doctor. During this visit your doctor will make sure you are well aware and have understood all the risks and advices related to the use of valproate during pregnancy.
• Your doctor will try to switch you to another medicine, or stop treatment with Episenta a long time before you become pregnant.
• Schedule an urgent appointment with your doctor if you are pregnant or think you might be pregnant.

Do not stop taking Episenta, unless your doctor tells you to as your condition may become worse. Schedule an urgent appointment with your doctor if you are pregnant or think you might be pregnant. Your doctor will advise you further.

Babies born to mothers who have been on valproate are at serious risk of birth defects and problems with development which can be seriously debilitating.

You will be referred to a specialist experienced in the management of bipolar disorder or epilepsy, so that alternative treatment options can be evaluated.

In the exceptional circumstances when Episenta is the only available treatment option during pregnancy, you will be monitored very closely both for the management of your underlying condition and to check how your unborn child is developing. You and your partner could receive counselling and support regarding the valproate exposed pregnancy.

Ask your doctor about taking folic acid. Folic acid can lower the general risk of spina bifida and early miscarriage that exists with all pregnancies. However, it is unlikely that it will reduce the risk of birth defects associated with valproate use.

Key messages:

• Schedule an urgent appointment with your doctor if you are pregnant or think you might be pregnant.
• Do not stop taking Episenta unless your doctor tells you to.
• Make sure you are referred to a specialist experienced in the treatment of epilepsy or bipolar disorder to evaluate the need for alternative treatment options.
• You must get thorough counselling on the risks of Episenta during pregnancy, including teratogenicity and developmental effects in children.
• Make sure you are referred to a specialist for prenatal monitoring in order to detect possible occurrences of malformations.

Make sure you read the patient guide that you will receive from your doctor. Your doctor will discuss the Annual Risk Acknowledgement Form and will ask you to sign it and keep it. You will also receive a Patient Card from your pharmacist to remind you of valproate risks in pregnancy.

Breast-feeding

A small amount of sodium valproate, the active substance of Episenta, gets into the breast milk. Talk to your doctor about whether you should breast-feed your baby.

Fertility

Episenta may decrease your fertility. However, single reports have shown that this effect is reversible after discontinuation of the medicine.

You may experience drowsiness when you first start taking Episenta, or if you are taking it with other medicines, such as other antiepileptic drugs or benzodiazepines. If affected you should not drive or operate machinery.

Episenta 150 mg: This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.

Episenta 300 mg: This medicine contains 41.4 mg sodium (main component of cooking/table salt) in each capsule. This is equivalent to 2 % of the recommended maximum daily dietary intake of sodium for an adult.

Your doctor may decide to adjust your dose.

You or your child may be taking other medicines for epilepsy at the same time as Episenta. If so, your doctor should gradually initiate treatment depending on your or your child’s condition.

Your doctor may increase the dose of Episenta by 5–10 mg for each kg of body weight each day depending on which other medicines you are taking.

If you take more Episenta than you should or if someone else accidentally takes your medicine contact your nearest casualty department or tell your doctor or pharmacist immediately. Remember to take the pack, this leaflet and any remaining capsules with you.

Take it as soon as you remember. If your next dose is due within 2 hours, take a single dose now and do not take the next dose. Do not take a double dose to make up for a forgotten dose.

Do not stop taking Episenta without consulting your doctor. If you stop, your seizures may return. You should continue to take Episenta for as long as your doctor tells you to.

Make sure you or your child keep your regular appointments for a check up. They are very important as your or your child’s dose may need to be changed. Episenta can change the levels of liver enzymes shown up in blood tests. This can mean that your or your child’s liver is not working properly. If you or your child go into hospital or visit another doctor or a dentist, tell them you are taking Episenta.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is sodium valproate.
• The other ingredients are calcium stearate, colloidal anhydrous silicon dioxide (methylated), ammonio methacrylate copolymer type B, sorbic acid, sodium hydroxide, ethyl cellulose, dibutyl sebacate, oleic acid, gelatin, sodium lauryl sulfate, indigo carmine (E 132) and (for 300 mg capsules only) quinoline yellow (E104).

Episenta 150 mg capsules are blue/transparent hard gelatine capsules containing white granules.

Episenta 300 mg capsules are green/transparent hard gelatine capsules containing white granules.

Each pack contains 30, 50, 100 or 200 capsules.

Not all pack sizes may be marketed.