Epilim 400mg Powder and Solvent for solution for injection/infusion

WARNING

Epilim Injection, sodium valproate, can seriously harm an unborn baby when taken during pregnancy. If you are a female able to have a baby, you should use an effective method of birth control (contraception) without interruption during your entire treatment with Epilim Injection. 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 Epilim Injection 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 Epilim Injection, you must also read section 2 of this leaflet carefully and contact your child’s doctor once they experience their first period.

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

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

What is in this leaflet

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

What Epilim Injection is

The name of your medicine is Epilim 400mg Powder and Solvent for solution for injection/infusion (called Epilim Injection in this leaflet).

What Epilim Injection contains

Epilim Injection contains a medicine called sodium valproate. This belongs to a group of medicines called anti-convulsants or anti-epileptic agents. It works by helping to calm the brain down.

What Epilim Injection is used for

Epilim Injection is used to treat epilepsy (fits) in adults and children. The injection is given when it is not possible to have your medicine by mouth.

Do not have Epilim Injection if:

• You are allergic (hypersensitive) to sodium valproate or any of the other ingredients of Epilim Injection (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 Injection unless you use an effective method of birth control (contraception) at all times during your treatment with Epilim Injection. Do not stop taking Epilim Injection 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 have this medicine if any of the above apply to you. If you are not sure, talk to your doctor, nurse or pharmacist before having Epilim Injection.

Warnings and precautions

• A small number of people being treated with anti-epileptics 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, nurse or pharmacist before having Epilim Injection 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, nurse or pharmacist before having Epilim Injection.

Weight gain

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

Blood tests

Your doctor may wish to do blood tests before you start having Epilim Injection and during your treatment.

Other medicines and Epilim Injection

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

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

• 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.

Epilim Injection may increase the effect of the following medicines:

• Medicines used for thinning the blood such as warfarin.
• Zidovudine used to treat HIV infection and AIDS.
• 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 Epilim Injection 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 to treat HIV infection and AIDS.
• Carbapenem agents (antibiotics used to treat bacterial infections) such as imipenem, meropenem, rifampicin and erythromycin. The combination of Epilim Injection and carbapenems should be avoided because it may decrease the effect of your medicine.
• Cholestyramine used to lower blood fat (cholesterol) levels.

Epilim Injection with alcohol

Alcohol intake is not recommended during treatment.

Pregnancy, breast-feeding and fertility

Important advice for women

• You must not use Epilim Injection if you are pregnant, unless nothing else works for you.
• If you are a woman able to have a baby, you must not take Epilim Injection unless you use an effective method of birth control (contraception) during your entire treatment with Epilim Injection.
• Do not stop taking Epilim Injection or your birth control (contraception), until you have discussed this with your doctor. Your doctor 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.
• It can cause serious birth defects and can affect the way in which the child develops as it grows. Birth defects which have been reported 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. Hearing problems or deafness have been reported in children exposed to valproate during pregnancy.
• 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 2-3 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 that you want to have a child, you should not stop taking your medicine or your method of birth control (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 their doctor once your child 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 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.

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

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

I AM STARTING TREATMENT WITH EPILIM INJECTION

If this is the first time you have been prescribed Epilim Injection 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 birth control (contraception) without interruption throughout your treatment with Epilim Injection.

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 Injection 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 Epilim Injection.
• 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 (contraception).
• You must get regular (at least annual) appointments with a specialist experienced in the management of epilepsy. During this visit your doctor 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 INJECTION AND NOT PLANNING TO HAVE A BABY

If you are continuing treatment with Epilim Injection but you are not planning to have a baby, make sure you are using an effective method of birth control (contraception) without interruption during your entire treatment with Epilim Injection. 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) during your entire treatment with Epilim Injection.
• You must discuss 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 doctor 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 INJECTION 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 Injection or your birth control (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 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 Epilim Injection, switch you to another medicine, or stop treatment with Epilim Injection a long time before you become pregnant – this is to make sure your illness is stable.

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.

Key messages:

• Do not stop taking Epilim Injection unless your doctor tells you to.
• Do not stop using your birth control (contraception) before you have talked to your doctor and worked together on a plan to ensure your epilepsy 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 of and have understood all the risks and advice related to the use of valproate during pregnancy.
• Your doctor will try to switch you to another medicine or stop treatment with Epilim Injection a long time before you become pregnant.
• Schedule an urgent appointment with your doctor if you are pregnant or think you might be pregnant.

AM PREGNANT AND I AM USING EPILIM INJECTION

Do not stop taking Epilim Injection 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 epilepsy so that alternative treatment options can be evaluated.

In the exceptional circumstances when Epilim Injection 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 Injection unless your doctor tells you to.
• Make sure you are referred to a specialist experienced in the treatment of epilepsy to evaluate the need for alternative treatment options.
• You must get thorough counselling on the risks of Epilim Injection during pregnancy, including malformations 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 doctor, nurse or 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 Injection gets into the breast milk. However, talk to your doctor about whether you should breast-feed your baby.

Ask your doctor, nurse or pharmacist for advice before taking or having any medicine.

Driving and using machines

You may feel sleepy when taking Epilim Injection. 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 Injection contains sodium

This medicine contains 55.35mg sodium (main component of cooking/table salt) in each vial. This is equivalent to less than 3% of the recommended maximum daily dietary intake of sodium for an adult per vial.

How much will be given to you

• Your doctor will decide how much to give you depending on your illness. The amount of Epilim Injection given to you or your child will depend on you or your child’s age or body weight.
• If you have been taking Epilim by mouth your doctor may decide to give you the same amount of Epilim Injection by continuous or repeated infusion.

If you have not had Epilim Injection before, the doctor will use the following doses:

Adults (including the elderly)

• The starting dose is usually 400-800mg (up to 10mg per kilogram of body weight).
• This is given as a slow intravenous injection over 3-5 minutes.
• This is followed by a continuous or repeated infusion, up to a maximum of 2500mg each day.

Children

• The usual dose is between 20-30mg for each kilogram of body weight each day.
• This may be increased to 40mg for each kilogram of body weight each day depending on your child’s illness.

Patients with kidney problems

• Your doctor may decide to adjust your or your child’s dose.

Patients taking other medicines for fits (epilepsy)

• You or your child may be taking other medicines for epilepsy at the same time as Epilim Injection. If so, your doctor should gradually initiate treatment depending on your or your child’s condition.
• Your doctor may increase the dose of Epilim Injection by 5-10mg for each kilogram of body weight each day depending on which other medicines you are taking.

If you have more Epilim Injection than you should

It is unlikely that your doctor or nurse will give you too much medicine. Your doctor will be checking your progress and checking the medicine that you are given. Always ask if you are not sure why you are getting a dose of medicine.

Using too much Epilim Injection can lead to the following symptoms: feeling sick or being sick, pupils of the eye become smaller, dizziness, loss of consciousness, weak muscles and poor reflexes, breathing problems, headaches, fits (seizures), confusion, memory loss and unusual or inappropriate behaviour.

If you forget to have Epilim Injection

Your doctor or nurse will have instructions on when to give you this medicine. It is unlikely that you will not be given the medicine as it has been prescribed. However, if you think you may have missed a dose, then talk to your doctor or nurse.

If you stop using Epilim Injection

It is important for you to keep having Epilim injection until your doctor decides to stop them. If you stop, your fits may come back.

Tests

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. Epilim Injection 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 Epilim Injection.

Tell your doctor straight away if you notice any of the following serious side effects – you may need urgent medical treatment:

• You have an allergic reaction. The signs may include: a rash, joint pain, fever (systemic lupus erythematosus), swallowing or breathing problems, swelling of your lips, face, throat or tongue. Hands, feet or genitals may also be affected. More severe allergic reactions can lead to lymph node enlargement and possible impairment of other organs.
• Liver problems and problems of the pancreas may show as a sudden illness which may happen in the first six months of treatment. This happens in a very small number of people taking Epilim Injection. It includes feeling and being sick many times; being very tired, sleepy and weak; stomach pain including very bad upper stomach pain; jaundice (yellowing of the skin or whites of the eyes); loss of appetite; swelling (especially of the legs and feet but may include other parts of the body); worsening of your fits or a general feeling of being unwell. Your doctor may tell you to stop taking Epilim Injection immediately if you have these symptoms.
• You have a skin rash or skin lesions with a pink/red ring and a pale centre which may be itchy, scaly or filled with fluid. The rash may appear especially on the palms or soles of your feet. These could be signs of a serious allergy to the medicine called ‘erythema multiforme’.
• Blistering or bleeding of the skin around the lips, eyes, mouth, nose and genitals. Also, flu-like symptoms and fever. This may be something called ‘Stevens-Johnson syndrome’.
• Severe blistering rash where layers of the skin may peel off to leave large areas of raw exposed skin over the body. Also, a feeling of being generally unwell, fever, chills and aching muscles. This may be something called ‘Toxic epidermal necrolysis’.
• Bruising more easily and getting more infections than usual. This could be a blood problem called ‘thrombocytopenia’. It can also be due to a fall in the number of white blood cells, bone marrow depression or another condition that affects red blood cells, white blood cells and platelets (pancytopenia) or how the blood clots.
• Blood clotting problems (bleeding for longer than normal), bruising or bleeding for no reason.
• Changes in mood, loss of memory, lack of concentration and deep loss of consciousness (coma).
• Underactive thyroid gland, which may cause tiredness or weight gain (hypothyroidism).
• Breathing difficulty and pain due to inflammation of the lungs (pleural effusion).

Tell your doctor as soon as possible if you have any of the following side effects:

• Changes in behaviour including being very alert, and sometimes also aggressive, hyperactive and unusual or inappropriate behaviour. This is more likely if other medicine to treat fits such as phenobarbital and topiramate are taken at the same time or if the Epilim Injection starting dose is high or has been suddenly increased.
• Changes in the amount of ammonia in the blood. Symptoms of this condition are being sick, problems with balance and co-ordination, feeling lethargic or less alert.
• Feeling shaky (tremor), sleepy or unsteady when walking or jerky muscle movements.
• Feeling tired or confused with loss of consciousness sometimes accompanied by hallucinations or fits.
• Blisters with the skin flaking away.
• Rapid, uncontrollable movement of the eyes.
• An increase in the number and severity of convulsions.

Tell your doctor, nurse or pharmacist if any of the following side effects get serious or lasts longer than a few days, or if you notice any side effects not listed in this leaflet:

• Feeling sick (nausea), being sick (vomiting), stomach ache or diarrhoea, especially when starting treatment.
• Swelling of gums or sore mouth
• Feeling dizzy
• Fainting
• Hearing loss
• Double vision
• Nail and nail bed disorders
• Skin problems such as rashes. These happen rarely, but more often in people also taking lamotrigine.
• Hair disorders (changes in texture, colour or growth), hair loss which is usually temporary. When it grows back it may be more curly than before.
• Increased levels of some hormones (androgens), which may lead to increased hair growth on the face, breasts or chest, acne or thinning hair.
• Skin rash caused by narrow or blocked blood vessels (vasculitis)
• Changes in women's periods and increased hair growth in women
• Breast enlargement in men
• Swelling of the feet and legs (oedema)
• Obesity, weight gain – as your appetite may be increased
• Kidney disease, kidney problems, blood in the urine, bedwetting or increased need to pass urine, urinary incontinence (unintentional passing of urine)
• Headache
• Seeing or hearing things that are not there (hallucinations)
• Aggression, agitation, disturbance in attention, abnormal behaviour, restlessness/hyperactivity and learning disorder
• Tingling or numbness of the hands or feet
• Lowering of normal body temperature
• Abnormal blood clotting factors
• Muscle pain and weakness (rhabdomyolysis)

Bone disorders

There have been reports of bone disorders including osteopenia and osteoporosis (thinning of the bone) and fractures. Check with your doctor, nurse or pharmacist if you are on long-term anti-epileptic medication, have a history of osteoporosis, or take steroids.

Tests

Epilim Injection can change levels of liver enzymes, salts or sugars shown up on blood and urine tests.

Male fertility

Epilim Injection can be a contributing factor in male infertility.

Additional side effects in children

Some side effects of valproate occur more frequently in children or are more severe compared to adults. These include liver damage, inflammation of the pancreas (pancreatitis), bedwetting (enuresis), renal dysfunction (Fanconi Syndrome), overgrowth of gum tissue, aggression, agitation, disturbance in attention, abnormal behaviour, hyperactivity and learning disorder.

Reporting of side effects

If you get any side effects, talk to your doctor, nurse or pharmacist. 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 for 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.

What Epilim Injection contains

Each vial contains 400mg of the active substance, sodium valproate.

What Epilim Injection looks like and contents of the pack

Epilim is a freeze-dried powder in a colourless glass vial with an aluminium cap. The vial is supplied packed in a carton along with one ampoule containing 4ml of water for injection.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Manufacturer :