Do not take Epilim Syrup if:

• You are allergic (hypersensitive) to sodium valproate or any of the other ingredients of Epilim Syrup (listed in section 6).
  Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.
• You have liver problems, or you or your family have a history of liver problems, especially if caused by taking a medicine.
• You have a rare illness called porphyria which affects your metabolism.
• You have a known metabolic disorder, i.e a urea cycle disorder.
• You have a genetic problem caused by a mitochondrial disorder (e.g. Alpers-Huttenlocher syndrome).
• You are pregnant, unless nothing else works for you (see ‘Pregnancy, breast-feeding and fertility – Important advice for women’ below).

If you are a woman able to have a baby, you must not take Epilim Syrup unless you use an effective method of birth control (contraception) at all times during your entire treatment with Epilim Syrup. Do not stop taking Epilim Syrup or your contraception until you have discussed this with your specialist. Your specialist 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 Epilim Syrup.

Warnings and precautions

• 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 anti-epileptic 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 Epilim Syrup if:

• You have a brain disease or a metabolic condition affecting your brain.
• You have problems with your pancreas.
• You have diabetes or are being tested for 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 monitor your valproate level or adjust your dose.
• 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 rare 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 Epilim Syrup.

Weight gain

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

Blood tests

Your doctor may do blood tests and liver function tests before and during your treatment with this medicine. Epilim Syrup 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.

Other medicines and Epilim Syrup

Tell your doctor or pharmacist 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 Epilim Syrup can affect the way some other medicines work. Also, some medicines can affect the way Epilim Syrup works.

In particular, check with your doctor if you are taking any of the following:

• 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, acetazolamide, lamotrigine and felbamate.
• Medicines used to calm emotional and mental health disorders (including schizophrenia, bipolar disorder and depression) such as quetiapine, diazepam and olanzapine.
• Monoamine oxidase inhibitors (MAOIs) such as moclobemide (used to treat depression and anxiety), selegiline (used to treat Parkinson’s disease), linezolid (used to treat infections).
• Anticoagulants such as warfarin – used to thin the blood and prevent clots. Your doctor may change your dose of the blood thinning medicine and monitor your treatment closely.
• Zidovudine and protease inhibitors such as lopinavir and ritonavir – used to treat HIV infection and AIDs.
• Carbapenem agents (antibiotics used to treat bacterial infections) such as panipenem, imipenem, meropenem, rifampicin and erythromycin. The combination of Epilim Syrup and carbapenems should be avoided because it may decrease the effect of your medicine.
• Some medicines used to treat or prevent malaria such as mefloquine and chloroquine.
• Temozolomide – used to treat cancer.
• Cimetidine – used to treat stomach ulcers.
• Cholestyramine – used to lower blood fat (cholesterol) levels.
• Nimodipine – used to treat bleeding in the brain (subarachnoid haemorrhage).
• Propofol – used for anaesthesia.
• Oestrogen-containing products (including some birth control pills).
• Metamizole – used to treat pain and fever.

Epilim Syrup with alcohol

Alcohol intake is not recommended during treatment.

Pregnancy, breast-feeding and fertility

Important advice for women

• You must not use Epilim Syrup if you are pregnant, unless your specialist has determined that no alternative treatment works for you.
• If you are a woman able to have a baby, you must not take Epilim Syrup unless you use an effective method of birth control (contraception) at all times during your entire treatment with Epilim Syrup.
• Do not stop taking Epilim Syrup or your birth control (contraception), until you have discussed this with your specialist. Your specialist will advise you further.

The risks of valproate when taken during pregnancy

• 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, including when valproate is used in combination with other medicines to treat epilepsy.
• It can cause serious birth defects and can affect the physical and mental development of the child as it grows after birth. If you take valproate during pregnancy you have a greater 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 11 babies in every 100 will have birth defects. This compares to 2-3 babies in every 100 born to women from the general population.
  • 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.
• It is estimated that up to 30-40% of 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.
  • Autism and related 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 specialist will have explained what might happen to your baby if you become pregnant whilst taking valproate. If you decide later that you want to have a baby, you must not stop taking your medicine or your method of birth control (contraception) until you have discussed this with your specialist.
• If you are a parent or a caregiver of a female child treated with valproate, you must contact their doctor once your child using valproate experiences their first period (menarche).
• 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.
• 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.

Please choose the situations which apply to you and read the descriptions below:

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

I AM STARTING TREATMENT WITH EPILIM SYRUP

If this is the first time you have been prescribed Epilim Syrup your specialist will have explained the risks to an unborn child if you become pregnant. Once you are able to have a baby, you must use an effective method of birth control (contraception) at all times during your entire treatment with Epilim Syrup. Talk to your doctor or family planning clinic if you need advice on birth control (contraception).

Key messages:

• Pregnancy must be excluded before start of treatment with Epilim Syrup with the result of a pregnancy test, confirmed by your specialist.
• You must use an effective method of birth control (contraception) at all times during your entire treatment with Epilim Syrup.
• You must discuss appropriate and effective 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 (contraception).
• You must get regular (at least annual) appointments with a specialist experienced in the management of epilepsy. During this visit your specialist will make sure you are well aware of and have understood all the risks and advice 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.

I AM TAKING EPILIM SYRUP AND NOT PLANNING TO HAVE A BABY

If you are continuing treatment with Epilim Syrup but you are not planning to have a baby, you must use an effective method of birth control (contraception) at all times during your entire treatment with Epilim Syrup. Talk to your doctor or family planning clinic if you need advice on birth control (contraception).

Key messages:

• You must use an effective method of birth control (contraception) at all times during your entire treatment with Epilim Syrup.
• You must discuss appropriate and effective 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 (contraception).
• You must get regular (at least annual) appointments with a specialist experienced in the management of epilepsy. During this visit your specialist will make sure you are well aware of and have understood all the risks and advice 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.

I AM TAKING EPILIM SYRUP AND PLANNING TO HAVE A BABY

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

Do not stop taking Epilim Syrup or your birth control (contraception) until you have discussed this with your specialist. Your specialist will advise you further.

Babies born to mothers who have been on valproate are at serious risk of birth defects and problems with development (behaviour and learning disorders), which can be seriously debilitating. Your doctor will refer you to a specialist experienced in the management of epilepsy, so that alternative treatment options are 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 Epilim Syrup, switch you to another medicine, or stop treatment with Epilim Syrup 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 Epilim Syrup unless your specialist tells you to.
• Do not stop using your birth control (contraception) before you have talked to your specialist and worked together on a plan to ensure your condition is controlled and the risks to you and your baby are reduced.
• First schedule an appointment with your specialist. During this visit your specialist will make sure you are well aware of and have understood all the risks and advice related to the use of valproate during pregnancy.
• Your specialist will try to switch you to another medicine or stop treatment with Epilim Syrup a long time before you become pregnant.
• Schedule an urgent appointment with your doctor if you are pregnant or think you might be pregnant.

I AM PREGNANT AND I AM TAKING EPILIM SYRUP

Do not stop taking Epilim Syrup unless your specialist 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 (behaviour and learning disorders) which can be seriously debilitating. You will be referred to a specialist experienced in the management of epilepsy so that alternative treatment options can be evaluated.

In the exceptional circumstances when Epilim Syrup 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 should 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 Epilim Syrup unless your specialist tells you to.
• Make sure you are referred to a specialist experienced in the treatment of epilepsy to evaluate the possibility of alternative treatment options.
• You must get thorough counselling on the risks of Epilim Syrup during pregnancy, including malformations and physical and mental development disorders in children.
• Make sure you are referred to a specialist for prenatal monitoring to examine for potential malformations.

Make sure you read the Patient Guide that you will receive from your doctor or pharmacist. Your specialist 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.

Newborn babies of mothers who took valproate during pregnancy may have:

• Blood clotting problems (such as blood not clotting very well). This may appear as bruising or bleeding which takes a long time to stop.
• Hypoglycaemia (low blood sugar).
• Hypothyroidism (underactive thyroid gland, which can cause tiredness or weight gain).
• Withdrawal syndrome (including agitation, irritability, hyperexcitability, jitteriness, hyperkinesia, muscle problems, tremor, convulsions and feeding problems). In particular, this may occur in newborns whose mothers have taken valproate during the last trimester of their pregnancy.

Breast-feeding

Very little Epilim Syrup gets into the breast milk. However, talk to your doctor about whether you should breast-feed your baby. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

You may feel sleepy when taking Epilim Syrup. If this happens to you, do not drive or use any tools or machines. Taking other medicines used to treat fits or calm emotional and mental health problems may increase sleepiness.

Epilim Syrup contains

• Sucrose: This medicine contains 3.5g per 5ml. People with diabetes need to take this into account. It may also be harmful to the teeth. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
• Sorbitol (E420): This medicine contains 647.5mg per 5ml. Sorbitol is a source of fructose. If your doctor has told you that you (or your child) have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you (or your child) take this medicine. Sorbitol may cause gastrointestinal discomfort and mild laxative effect.
• Sodium: This medicine contains 27.7mg sodium (main component of cooking/table salt) per 5ml. This is equivalent to less than 2% of the recommended maximum daily dietary intake of sodium for an adult per 5ml.