• Keep this leaflet. You may need to read it again.
• If you have further questions, please 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 are 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 Dyzantil is and what it is used for
2. What you need to know before you take Dyzantil
3.How to take Dyzantil
4.Possible side effects
5.How to store Dyzantil
6.Contents of the pack and other information

The name of your medicine is Dyzantil 200, 300 and 500mg prolonged-release tablets. “Prolonged-release” means that the active ingredient sodium valproate is slowly released from the tablets over a period of time.

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

Dyzantil is used to treat epilepsy (fits) in adults and children.

• You are allergic (hypersensitive) to sodium valproate or any of the other ingredients of Dyzantil (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 Dyzantil unless you use an effective method of birth control (contraception) at all times during your treatment with Dyzantil. Do not stop taking Dyzantil 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 Dyzantil.

• 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 or pharmacist before taking Dyzantil if:

• You have a brain disease or a metabolic condition affecting your brain.
• You have problems with your pancreas.
• 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 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 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 Dyzantil.

Taking Dyzantil 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 Dyzantil and during your treatment with this medicine. Dyzantil 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.

Please tell your doctor 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 Dyzantil can affect the way some other medicines work. Also, some medicines can affect the way Dyzantil 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 problems (including schizophrenia, bipolar disorder and depression) such as quetiapine, diazepam and olanzapine.
• Monoamine oxidase inhibitors (MAOI) 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 imipenem, meropenem, rifampicin and erythromycin. The combination of Dyzantil and carbapenems should be avoided because it may decrease the effect of your medicine.
• Some medicines used for the prevention and treatment of malaria such as mefloquine and chloroquine.
• Temozolomide used to treat cancer.
• Cimetidine used for 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, a medicine used to treat pain and fever.

Alcohol intake is not recommended during treatment.

Important advice for women

• You must not use Dyzantil 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 Dyzantil unless you use an effective method of birth control (contraception) during your entire treatment with Dyzantil.
• Do not stop taking Dyzantil 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, 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 10 babies in every 100 will have birth defects. This compares to 2-3 babies in ever 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 valporate 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 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 and related disorders are more often diagnosed in children exposed to valproate during pregnancy and there is some evidence children exposed to valproate during pregnancy are at increased risk of developing symptoms of 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 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 DYZANTIL
• I AM TAKING DYZANTIL AND NOT PLANNING TO HAVE A BABY
• I AM TAKING DYZANTIL AND PLANNING TO HAVE A BABY
• I AM PREGNANT AND I AM TAKING DYZANTIL

I AM STARTING TREATMENT WITH DYZANTIL

If this is the first time you have been prescribed Dyzantil 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) at all times during your entire treatment with Dyzantil. 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 Dyzantil 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 Dyzantil.
• You must discuss 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 DYZANTIL AND NOT PLANNING TO HAVE A BABY

If you are continuing treatment with Dyzantil but you are not planning to have a baby, make sure you are using an effective method of birth control (contraception) at all times during your entire treatment with Dyzantil. 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 Dyzantil.
• 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 DYZANTIL 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 Dyzantil 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 (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 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 Dyzantil, switch you to another medicine, or stop treatment with Dyzantil 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 Dyzantil 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 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 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 Dyzantil 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 USING DYZANTIL

Do not stop taking Dyzantil 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 (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 Dyzantil 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 Dyzantil 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 Dyzantil 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 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 Dyzantil 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.

You may feel sleepy when taking Dyzantil. 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.

Dyzantil 200 contains 18.43mg sodium (main component of cooking/table salt) in each tablet. This is equivalent to less than 1% of the recommended maximum daily dietary intake of sodium for an adult per tablet.

Dyzantil 300 contains 27.65mg sodium (main component of cooking/table salt) in each tablet. This is equivalent to less than 2% of the recommended maximum daily dietary intake of sodium for an adult per tablet.

Dyzantil 500 contains 46.08mg sodium (main component of cooking/table salt) in each tablet. This is equivalent to less than 3% of the recommended maximum daily dietary intake of sodium for an adult per tablet.

• Take this medicine by mouth. Do not crush or chew the tablets.
• Take Dyzantil with or after food. This will help to stop the feelings of sickness that may happen after taking Dyzantil.
• This medicine can be taken once or twice daily.
• You may see what appears to be part of the tablet in your stool. This is normal as the matrix of Dyzantil is not digested by the body. It does not mean that the medicine is not working.

Adults (including the elderly)

• The starting dose is 600mg daily. Your doctor will gradually increase this dose by 200mg every 3 days depending on your condition.
• The usual dose is generally between 1000mg and 2000mg (20-30mg per kilogram of body weight) each day.
• This may be increased to 2500mg each day depending on your illness.

Children over 20 kilograms

• The starting dose should be 400mg daily. Your doctor should increase this dose depending on your child’s illness.
• The usual dose is then between 20mg and 30mg for each kilogram of body weight each day.
• This may be further increased to 35mg for each kilogram of body weight each day depending on your child’s illness.

Children under 20 kilograms

• Dyzantil is not recommended in children that weigh less than 20 kilograms. Liquid formulations of sodium valproate are recommended instead.

Patients with kidney problems

• Your doctor may decide to adjust your dose 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 Dyzantil. If so, your doctor should gradually initiate treatment depending on your or your child’s condition.
• Your doctor may increase the dose of Dyzantil by 5-10mg for each kilogram of body weight each day depending on which other medicines you are taking.

If you take more Dyzantil than you should, tell a doctor or go to a hospital casualty department straight away. Take the medicine pack with you. This is so the doctor knows what you have taken.

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

If you or your child forget to take a dose, take it as soon as you remember. However, if it is nearly time for the next dose, skip the missed dose. Do not take a double dose to make up for a forgotten dose.

Do not stop taking Dyzantil or alter your or your child’s dose without checking with your specialist. If you or your child stop taking Dyzantil without your specialist’s advice, 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 are taking Dyzantil.

• 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 Dyzantil. 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 Dyzantil 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 Dyzantil 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 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), stomach ache or diarrhoea, especially when starting treatment. This may be helped by taking the tablets with food.
• 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, acne or thinning hair.
• Skin rash caused by narrow or blocked 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).
• Seeing or hearing things that are not there (hallucinations).
• Aggression, agitation, disturbance in attention, abnormal behaviour, restlessness/hyperactivity, and 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.

Dyzantil can change levels of liver enzymes, 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, 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 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 200mg prolonged-release tablet contains a mixture of 133.2mg sodium valproate and 58mg valproic acid, equivalent to 200mg of the active substance sodium valproate.
• Each 300mg prolonged-release tablet contains a mixture of 199.8mg sodium valproate and 87mg valproic acid, equivalent to 300mg of the active substance sodium valproate.
• Each 500mg prolonged-release tablet contains a mixture of 333mg sodium valproate and 145mg valproic acid, equivalent to 500mg of the active substance, sodium valproate.

The other ingredients are:

• For Dyzantil 200mg and 500mg prolonged-release tablets: hypromellose (E464), ethylcellulose, hydrated silica, titanium dioxide (E171), erythrosine aluminium lake (E127), indigo carmine aluminium lake (E132), iron oxide black (E172), macrogol 400.
• For Dyzantil 300mg prolonged-release tablets: hypromellose (E464), ethylcellulose, hydrated silica, titanium dioxide (E171), indigo carmine aluminium lake (E132), iron oxide black (E172), macrogol 400.

• Dyzantil 200mg and 500mg prolonged-release tablets: Violet coloured, oblong shaped, prolonged-release tablets, plain on both sides.
• Dyzantil 300mg prolonged-release tablets: Blue coloured, oblong shaped, prolonged-release tablets, plain on both sides.

Pack sizes:

14, 30, 48, 72, 90, 100 prolonged-release tablets.

Not all pack sizes may be marketed.

This leaflet does not contain all the information about your medicine. If you have any questions or are not sure about anything, ask your doctor or pharmacist.