Sodium Valproate 400 mg Powder and solvent for solution – patient leaflet, side effects, dosage

1. What Sodium Valproate is and what it is used for

What Sodium Valproate contains

Sodium Valproate 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 Sodium Valproate is used for

Sodium Valproate 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.

2. What you need to know before you are given Sodium Valproate

Do not use Sodium Valproate:

• if you are allergic(hypersensitive) to sodium valproate

  or any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.

• if you have liver problems, or you or your family have a

  history of liver problems, especially if caused by taking a medicine.

• if you have a rare illness called porphyria which affects your

  metabolism.

• if you have a known metabolic disorder, i.e a urea cycle

  disorder.

• if you have a genetic problem caused by a mitochondrial

  disorder (e.g. Alpers-Huttenlocher syndrome).

• if you have a deficiency in carnitine (a very rare metabolic

  disease) that is untreated.

• if 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 use Sodium Valproate unless you use an effective method of birth control (contraception) at all times during your entire treatment with Sodium Valproate. Do not stop using Sodium Valproate 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 use this medicine if any of the above apply to you. If you are not sure, talk to your doctor, nurse or pharmacist before having Sodium Valproate.

Warnings and precautions

• The risk of liver damage is increased if Sodium Valproate

  is used 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 using Sodium Valproate 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.

• Serious skin reactions including Stevens-Johnson

  syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme and angioedema have been reported in association with valproate treatment. Seek medical attention immediately if you notice any of the symptoms related to these serious skin reactions described in section 4.

Talk to your doctor, pharmacist or nurse before you are given Sodium Valproate 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 diary 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 immune system which affects skin, bones, joints and internal organs.

• You have ever developed a severe skin rash or skin

  peeling, blistering and/or mouth sores after taking valproate. If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before having Sodium Valproate.

Weight gain

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

Blood tests

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

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 Sodium Valproate can affect the way some other medicines work. Also, some medicines can affect the way Sodium Valproate 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 an 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 Sodium Valproate 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.
  • Clozapine – used to treat mental health conditions.

Sodium Valproate with alcohol

Alcohol intake is not recommended during treatment.

Pregnancy, breast-feeding and fertility

Important advice for women

• You must not use Sodium Valproate 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

  Sodium Valproate unless you use an effective method of birth control (contraception) at all times during your entire treatment with Sodium Valproate.

• Do not stop taking Sodium Valproate or your birth control

  (contraception), until you have discussed this with your specialist. Your specialist will advise you further.

The risks of valproate when given 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 use 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).

  • If you take valproate during pregnancy, your baby may have a lower weight than expected for their age at birth
• 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:

o I AM STARTING TREATMENT WITH SODIUM

VALPROATE

o I AM HAVING SODIUM VALPROATE AND NOT PLANNING

TO HAVE A BABY

o I AM HAVING SODIUM VALPROATE AND PLANNING TO

HAVE A BABY

o I AM PREGNANT AND I AM HAVING SODIUM

VALPROATE

I AM STARTING TREATMENT WITH SODIUM VALPROATE

If this is the first time you have been prescribed Sodium Valproate 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 Sodium Valproate. 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 Sodium Valproate 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 Sodium Valproate.

• 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 GIVEN SODIUM VALPROATE AND NOT PLANNING TO HAVE A BABY

If you are continuing treatment with Sodium Valproate 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 Sodium Valproate. 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 Sodium Valproate.

• 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 GIVEN SODIUM VALPROATE 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 Sodium Valproate 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. Babies are also at risk of lower weight than expected for their age at birth. 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 Sodium Valproate, switch you to another medicine, or stop treatment with Sodium Valproate 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 Sodium Valproate 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 Sodium Valproate 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 GIVEN SODIUM VALPROATE

Do not stop taking Sodium Valproate unless your specialist tells you to as your condition may become worse.

Arial 9pt 160 x 840 mm

The following information is intended for healthcare professionals only:

Sodium Valproate 400 mg Powder and solvent for solution for injection/infusion

Each vial of freeze-dried powder contains 400 mg of the active substance sodium valproate.

Each ampoule of solvent contains 4 mL of Water for Injection. Each 1 mL of the reconstituted solution contains 95 mg of the active substance sodium valproate.

Sodium Valproate may be given by direct slow intravenous injection or by infusion using a separate intravenous line in normal saline, dextrose 5%, or dextrose saline.

Posology

Daily dosage requirements vary according to age and body weight.

Each vial of Sodium Valproate is for single dose injection only.

Adults

Patients already satisfactorily treated with Sodium Valproate may be continued at their current dosage using continuous or repeated infusion. Other patients may be given a slow intravenous injection over 3 – 5 minutes, usually 400 – 800 mg depending on body weight (up to 10 mg/kg) followed by continuous or repeated infusion up to a maximum of 2500 mg/day.

Sodium Valproate Intravenous should be replaced by oral sodium valproate therapy as soon as practicable.

Special populations

Paediatric population

The safety profile of valproate in the paediatric population is comparable to adults, but some ADRs are more severe or principally observed in the paediatric population. There is a

particular risk of severe liver damage in infants and young children especially under the age of 3 years. Young children are also at particular risk of pancreatitis. These risks decrease with increasing age (see Section 4.4). Psychiatric disorders such as aggression, agitation, disturbance in attention, abnormal behaviour, psychomotor hyperactivity and learning disorder are principally observed in the paediatric population. Post-marketing Fanconi Syndrome, enuresis and gingival hyperplasia have been reported more frequently in paediatric patients than in adult patients. Daily requirement for children is usually in the range 20 – 30 mg/kg/day and method of administration is as above. Where adequate control is not achieved within this range the dose may be increased up to 40 mg/kg/day but only in patients in whom plasma valproic acid levels can be monitored. In children requiring dosed higher than 40 mg/kg/day clinical chemistry and haematological parameters should be monitored.

Elderly

Although the pharmacokinetics of sodium valproate are modified in the elderly, they have limited clinical significance and dosage should be determined by seizure control. The volume of distribution is increased in the elderly and because of decreased binding to serum albumin, the proportion of free drug is increased. This will affect the clinical interpretation of plasma valproic acid levels.

Renal impairment

It may be necessary in patients withrenal insufficiency to decrease the dosage, or to increase the dosage in patients on haemodialysis. Valproate is dialysable (sse section 4.9). Dosing should be modified according to clinical monitoring of the patient (see section 4.4).

Hepatic impairment

Salicylates should not be used concomitantly with valproate since they employ the same metabolic pathway.

Liver dysfunction, including hepatic failure resulting in fatalities, 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 Sodium Valproate 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 Sodium Valproate 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 Sodium

  Valproate 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, pharmacist or nurse. 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 sodium valproate 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.

Important advice for male patients

Potential risks related to taking valproate in the 3 months before conception of a child.

A study suggests a possible risk of neurodevelopmental conditions (problems with early childhood development) in children born to fathers treated with valproate in the 3 months before conception. In this study, around 5 children in 100 had such disorders when born to fathers treated with valproate as compared to around 3 children in 100 when born to fathers treated with lamotrigine or levetiracetam (other medicines that can be used to treat your disease).

Other studies did not suggest an increased risk of mental developmental disorders (problems with early childhood development) in children born to fathers treated with valproate in the 3-4 months before conception. In these studies the risk was similar compared to children of fathers treated with lamotrigine or levetiracetam before conception.

Differences in how these studies were designed may explain the different results. Overall, it is not known whether any possible risk of childhood developmental disorders is caused by valproate itself or by other factors, such as the father’s underlying medical condition.

As a precautionary measure, your GP or specialist will discuss with you:

• The potential risk in children born to fathers treated with

  valproate

• The need to consider effective contraception (birth control)

  for you and your female partner during treatment and for 3 months after stopping treatment

• The need to consult your specialist when you are planning

  to conceive a child and before stopping contraception (birth control)

• The possibility of other treatments that can be used to treat

  your disease, depending on your individual situation

Do not donate sperm when taking valproate or for 3 months after stopping valproate.

Talk to your GP or specialist if you are thinking about having a baby.

If your female partner becomes pregnant while you used valproate in the 3 months period before conception and you have questions, contact your GP or specialist. Do not stop your treatment without talking to your GP or specialist. If you stop your treatment, your symptoms may become worse.

You should get regular appointments with your GP. During this visit your GP will discuss with you the precautions associated with valproate use. They will refer you to a specialist to discuss the possibility of other treatments that can be used to treat your disease, depending on your individual situation.

Driving and using machines

You may feel sleepy when taking Sodium Valproate. 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.

Sodium Valproate contains sodium

This medicine contains 55 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 2.75% of the recommended maximum daily dietary intake of sodium for an adult.

3. How Sodium Valproate is given

Sodium Valproate is always given to you by a doctor or nurse. This is because it needs to be given as a slow injection or infusion into the vein.

If you are not sure why you are being given Sodium Valproate or have any questions about how much Sodium Valproate is being given to you, speak to your doctor or nurse.

Your doctor will stop giving you Sodium Valproate Injection and change you to sodium valproate tablets, granules, syrup or liquid as soon as possible.

Sodium Valproate treatment must be started and supervised by a doctor specialised in the treatment of epilepsy.

How much will be given to you

• Your doctor will decide how much to give you depending on

  your illness. The amount of Sodium Valproate given to you or your child will depend on you or your child’s age or body weight.

• If you have been taking sodium valproate by mouth your

  doctor may decide to give you the same amount of Sodium Valproate Injection by continuous or repeated infusion.

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

Adults (including the elderly)

• The starting dose is usually 400-800 mg (up to 10 mg 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 2500 mg each day.

Children

• The usual dose is 20-30 mg for each kilogram of body

  weight each day.

• This may be increased to 40 mg 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 Sodium Valproate. If so, your doctor should gradually initiate treatment depending on your or your child’s condition.

• Your doctor may increase the dose of Sodium Valproate

  by 5-10 mg for each kilogram of body weight each day depending on which other medicines you are taking.

If you use more Sodium Valproate 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.

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.

If you forget to use Sodium Valproate

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 Sodium Valproate

It is important for you to keep having Sodium Valproate until your specialist decides to stop them. If you stop using Sodium Valproate before your specialist decised to stop it, your condition may get worse.

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.

If you or your child go into hospital or visit another doctor or a dentist, tell them you have been given Sodium Valproate. If you have any further questions on the use of this product, ask your doctor, nurse or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Side effects are more likely to happen at the start of treatment.

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 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 Sodium Valproate. 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 Sodium Valproate 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)
• Difficulty breathing, pain or pressure in the chest (especially when breathing in), shortness of breath and dry cough due to buildup of fluid around 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’

Tell your doctor 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), 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

  • Darker areas of skin and mucosae (hyperpigmentation)
• 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.

Tests

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

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, 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,

Website: 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.

5. How to store Sodium Valproate

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month.

Only clear solutions free of particles should be used. Once diluted, Sodium Valproate should be stored in a refrigerator between 2-8° C and used within 24 hours.

Any solution remaining after 24 hours should be discarded. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Sodium Valproate contains

• The active substance is sodium valproate. Each vial contains 400 mg of the active substance, sodium valproate.
• The other excipients are hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and sodium chloride.

What Sodium Valproate looks like and contents of the pack

Sodium Valproate is a freeze-dried powder in a colourless glass vial with an aluminium cap. Sodium Valproate is available in packs of 1 glass vial with 1 glass ampoule solvent, 4 glass vials with 4 glass ampoules solvent and 5 glass vials with 5 glass ampoules solvent.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder:

Noridem Enterprises Ltd, Evagorou and Makariou, Mitsi Building 3, Office 115, 1065 Nicosia, Cyprus. Manufacturer:

DEMO S.A. PHARMACEUTICAL INDUSTRY, 21st km National Road Athens-Lamia, 14568 Krioneri, Attiki, Greece, T: +30 210 8161802, F: +30 2108161587.

This leaflet was last revised in 09/2026.

has occurred in patients whose treatment included valproic acid.

Salicylates should not be used in children under 16 years of age. In addition in conjunction with valproate, concomitant use in children under 3 years of age can increase the risk of liver toxicity.

Female children and women of childbearing potential Valproate must be initiated and supervised by a specialist experienced in the management of epilepsy.

Valproate should not be used in female children and women of childbearing potential unless other treatments are ineffective or not tolerated.

Valproate is prescribed and dispensed according to the Valproate Pregnancy Prevention Programme. The benefits and risks should be carefully reconsidered at regular treatment reviews.

Valproate should preferably be prescribed as monotherapy and at the lowest effective dose, if possible as a prolonged release formulation. The daily dose should be divided into at least two single doses.

Valproate is prescribed and dispensed according to the Valproate Pregnancy Prevention Programme.

Combined therapy

When starting Sodium Valproate in patients already on other anti-convulsants, these should be tapered slowly, initiation of Sodium Valproate therapy should then be gradual, with target dose being reached after about 2 weeks. In certain cases it may be necessary to raise the dose by 5 -10 mg/kg/day when used in combination with anti-convulsants which induce liver enzyme activity, e.g. phenytoin, phenobarbital and carbamazepine. Once known enzyme inducers have been withdrawn it may be possible to maintain seizure control on

a reduced dose of Sodium Valproate. When barbiturates are being administered concomitantly and particularly if sedation is observed (particularly in children) the dosage of barbiturate should be reduced.

Optimum dosage is mainly determined by seizure control and routine measurement of plasma levels is unnecessary. However, a method for measurement of plasma levels is available and may be helpful where there is poor control or side effects are suspected.

Incompatibilities

Sodium Valproate should not be administered via the same line as other IV additives.

Instructions for use and handling

For intravenous use, the reconstituted solution should be used immediately and any unused portion discarded.

If the reconstituted solution is further diluted for use as an infusion solution, the dilute solution may be stored for up to 24 hours if kept at 2 to 8° C before use, discarding any remaining after 24 hours.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Special precautions for storage

This medicinal product does not require any special storage conditions.

Reconstituted infusion solutions: at 2° C – 8° C if stored before use, discarding any remaining solution after 24 hours.