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 must use an effective method of birth control (contraception) at all times 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 or nurse if you want to become pregnant or if you think you are pregnant.

Do not stop taking Epilim Injection unless your specialist 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 or nurse once they experience their first period.

• 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.

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

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

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.

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.

• 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 have a deficiency in carnitine (a very rare metabolic disease) that is untreated.
• 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 entire treatment with Epilim Injection. Do not stop taking Epilim Injection 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 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.

• The risk of liver damage is increased if Epilim Injection is taken by children under 3 years of age, in people taking other antiepileptic medicine at the same time or having other neurological or metabolic disease and severe forms of epilepsy.
• 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.
• If you or your child taking Epilim Injection develops problems with balance and co-ordination, feeling lethargic or less alert, vomiting, tell your doctor immediately. This may be due to an increased amount of ammonia in the blood.

Talk to your doctor, nurse or pharmacist before taking Epilim Injection 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 know or your doctor suspects that there is a genetic problem caused by a mitochondrial disorder in your family, because of a risk of damage to your liver.
• You are suspected to suffer from any metabolic disorders, particularly hereditary enzyme deficiency disorders such as a “urea cycle disorder” because of a risk of increased ammonia level in the blood.
• You have a rare disorder named ‘carnitine palmitoyltransferase type II deficiency’, because you are at an increased risk of muscle disorders.
• You have impaired dietary intake in carnitine, found in meat and dairy products, especially in children less than 10 years old.
• You have a deficiency in carnitine and are taking carnitine.
• You have kidney problems. Your doctor may monitor your valproate level or adjust your dose.
• You have an illness called ‘systemic lupus erythematosus (SLE)’ – a rare disease of the imune system which affects skin, bones, joints and internal organs.

If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before having Epilim Injection.

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

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

Tell your doctor, nurse 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 Injection can affect the way some other medicines work. Also, some medicines can affect the way Epilim Injection 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.
• Cannabidiol (used to treat epilepsy and other conditions).
• 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 Injection and carbapenems should be avoided because it may decrease the effect of your medicine.
• Some anti-infectives that contain pivalate (e.g., pivampicillin, adefovir dipivoxil).
• 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.
• Methotrexate – used to treat cancer and inflammatory diseases.

Alcohol intake is not recommended during treatment.

Important advice for women

• You must not use Epilim Injection 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 Injection unless you use an effective method of birth control (contraception) at all times 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 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 therisks 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 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 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 or nurse 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 INJECTION
• I AM HAVING EPILIM INJECTION AND NOT PLANNING TO HAVE A BABY
• I AM HAVING EPILIM INJECTION AND PLANNING TO HAVE A BABY
• I AM PREGNANT AND I AM HAVING EPILIM INJECTION

I AM STARTING TREATMENT WITH EPILIM INJECTION

If this is the first time you have been prescribed Epilim Injection 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 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 specialist.
• You must use an effective method of birth control (contraception) at all times during your entire treatment with Epilim Injection.
• 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 HAVING 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, you must use an effective method of birth control (contraception) at all times 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) at all times during your entire treatment with Epilim Injection.
• 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 HAVING 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 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 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 or nurse 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 Injection 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 epilepsy 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 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.

I AM PREGNANT AND I AM HAVING EPILIM INJECTION

Do not stop taking Epilim Injection 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 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 or nurse 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 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 Injection 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, nurse 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 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.

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.

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.

• 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.

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 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.

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.

The following effects may happen: feeling sick or being sick, headache, blurred vision due to pupil of the eye becoming smaller, dizziness, poor reflexes, confusion, memory loss and tiredness. You may also have weak or ‘floppy muscles’, fits (seizures), loss of consciousness, behavioural changes and breathing difficulties such as fast breathing, shortness of breath or chest pain.

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.

It is important for you to keep having Epilim Injection until your specialist decides to stop them. If you stop having Epilim Injection before you specialist decides to stop it, your condition may get worse.

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. If you or your child go into hospital or visit another doctor or a dentist, tell them you have been given Epilim Injection.

• You have an allergic reaction which may manifest as:
  • Blisters with skin detachment (blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet) with or without rash), sometimes with flu-like symptoms such as fever, chills, or aching muscles. These may be signs of conditions named ‘Toxic epidermal necrolysis’ or ‘Stevens-Johnson Syndrome’.
  • 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 may be signs of a condition named ‘erythema multiforme’.
  • Allergy-triggered swelling with painful itchy welts (most often around the eyes, lips, throat and sometimes hands and feet) and swallowing or breathing problems. These may be signs of ‘angioedema’ or an anaphylactic reaction.
  • Syndrome with skin rash, fever, lymph node enlargement and possible impairment of other organs. These may be signs of a condition named ‘Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)’.
• 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 sick (nausea) and being sick (vomiting) many times; extreme tiredness, drowsiness and weakness; stomach pain including severe upper stomach pain; yellowing of the skin or whites of the eyes (jaundice); loss of appetite; swelling of the legs and feet (may also 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.
• Blood disorders that can be shown in blood tests. Signs may include:
  • Spontaneous bruising or bleeding due to blood clotting problems or decreased platelet count, or getting more infections than usual (thrombocytopenia)
  • Severe decrease of white blood cells or bone marrow failure, sometimes revealed by fever and breathing difficulty (agranulocytosis)
  • Decreased red blood cell count (anaemia) or abnormally increased red blood cell size (macrocytosis)
  • Bone marrow disorders that affect red blood cells, white blood cells and platelets (pancytopenia)
• Drowsiness, change in consciousness level (including coma), confusion, loss of memory, abnormal behaviour including changes in attention, concentration and mood. This could also be associated with hallucinations or more frequent or severe fits. 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.
• Underactive thyroid gland, which may cause tiredness or weight gain (hypothyroidism)
• Breathing difficulty and pain due to inflammation of the envelope of the lungs (pleural effusion)
• An increase in the number and severity of convulsions
• Muscle pain and weakness (rhabdomyolysis)
• Joint pain, fever, fatigue or rash. These may be signs of systemic lupus erythematosus (SLE).
• Problems with balance and co-ordination, feeling lethargic or less alert, associated with being sick (vomiting). This may be due to an increased amount of ammonia in your blood.
• Shakiness (tremor), jerky muscle movements, unsteadiness when walking (parkinsonism, extrapyramidal disorder, ataxia)
• Rapid, uncontrollable movement of the eyes
• Kidney disease or kidney problems (renal failure, tubulointerstitial nephritis and Fanconi syndrome) which may manifest as reduced urinary output or blood in the urine
• Confusion, that could be due to decreased levels of sodium in your blood, identified by a blood test, or to a condition named ‘Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion’

• Feeling sick (nausea), being sick (vomiting), stomachache or diarrhoea, especially when starting treatment.
• Overgrowth of gums (gingival hypertrophia), swelling of gums or mouth, sore mouth, mouth ulcers and burning feeling of mouth (stomatitis)
• Headache
• Hearing loss, hearing problems or deafness
• Double vision
• Nail and nail bed disorders
• Skin problems such as rashes. These happen rarely, but more often in people also taking lamotrigine.
• Transient hair loss, abnormal hair growth, abnormal hair texture, changes in hair colour
• Increased levels of some hormones (androgens), which may lead to increased hair growth on the face, breasts or chest (particularly in women), acne or thinning hair
• Skin rash caused by inflammation of small blood vessels (vasculitis)
• Irregularity or absence of women’s period, pain during women’s period, cysts in the ovaries (polycystic ovaries)
• Breast enlargement in men, male infertility (usually reversible after treatment discontinuation and may be reversible after dose reduction. Do not stop your treatment without speaking to your doctor first)
• Swelling of the feet and legs (oedema)
• Obesity, weight gain - as your appetite may be increased
• Bedwetting or increased need to pass urine, urinary incontinence (unintentional passing of urine)
• Passing a lot of urine and feeling thirsty (Fanconi syndrome)
• Decrease in carnitine levels (shown in blood or muscular tests)
• Seeing, feeling or hearing things that are not there (hallucinations)
• Aggression, agitation, disturbance in attention, abnormal behaviour, restlessness/hyperactivity, memory impairment, or cognitive or learning disorder
• Tingling or numbness in the hands and feet
• Lowering of normal body temperature

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

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

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.

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.

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

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.

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