Package leaflet: Information for the user Sodium Valproate Teva 200 and 500 mg Gastro-resistant Tablets

VThis medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

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

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor 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 seem 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.

What is in this leaflet

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

2.    What you need to know before you take Sodium Valproate

3.    How to take Sodium Valproate

4.    Possible side effects

5.    How to store Sodium Valproate

6.    Contents of the pack and other information

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

Sodium Valproate Teva Gastro-resistant Tablets contain the active ingredient Sodium Valproate, which belongs to a group of medicines known as anticonvulsants.

Sodium Valproate is a medicine for the treatment of epilepsy and mania. Sodium Valproate may be taken either on its own as your only treatment for epilepsy or you may take it together with another epilepsy therapy.

Sodium Valproate is used in the treatment of mania, where you may feel very excited, elated, agitated, enthusiastic or hyperactive. Mania occurs in an illness called ‘bipolar disorder’. Sodium Valproate can be used when lithium can not be used.

You must talk to a doctor if you do not feel better or if you feel worse within a few days of taking this medicine.

2. What you need to know before you take Sodium Valproate Do not take Sodium Valproate:

•    if you are allergic to Sodium Valproate or any of the other ingredients of this medicine

•    if you suffer from, or there is a family history of liver disease

•    if you suffer from porphyria (a deficiency of specific enzymes within the body, causing an increase of substances known as porphyrins).

•    If you have a genetic problem causing a mitochondrial disorder (e.g. Alpers-Huttenlocher syndrome) Warnings and precautions

A small number of people being treated with anti-epileptics such as Sodium Valproate have had thoughts of harming or killing themselves. If at any time you have these thoughts, immediately contact your doctor.

Talk to your doctor or pharmacist before taking Sodium Valproate

•    if you have severe fits or suffer from brain disease or a metabolic condition affecting your brain

•    if you suffer from kidney problems

•    if you suffer from systemic lupus erythematosus (an immune system condition affecting skin, bones and joints, lungs, or kidneys)

•    if you are diabetic, as Sodium Valproate may give an indication that ketones are present in the urine when this is not the case

•    if you have any metabolic disorders, particularly hereditary enzyme deficiency disorders such as a urea cycle disorder because of the risk of increased ammonia level in the blood

•    if you have an increased appetite and are putting on weight. Please regularly check your body weight when you are on this medicine.

•    if you know that there is a genetic problem causing a mitochondrial disorder in your family.

Children and adolescents

Children and adolescents under 18 years of age:

Sodium Valproate should not be used for children and adolescents below 18 years of age for the treatment of mania.

Weight gain

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

Blood tests

Your doctor may wish to do blood tests before you start and during the first six months of your treatment to:

•    check your levels of Sodium Valproate

•    check for blood or liver problems, especially in children under 3 years of age, or patients who suffer from severe seizures, have brain disease and/or learning disabilities, or have a history of liver disease.

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

Other medicines and Sodium Valproate

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

•    any other anti-epileptics e.g. phenytoin, phenobarbital, carbamazepine, lamotrigine, topiramate, primidone, felbamate

•    any anti-depressant medicines including monoamine oxidase inhibitors (MAOI) such as moclobemide, selegiline, linezolid

•    anti-psychotic agents - for mental health problems. Sodium Valproate may increase the effects of these drugs. In particular, when taken with the medicine olanzapine the following effects may occur: neutropenia (a blood problem which reduces the chance of fighting infection), tremor, dry mouth, increased appetite and weight gain, problems with speech, sleepiness or extreme tiredness

•    Medicines used to calm emotional and mental conditions such as diazepam and olanzapine

•    antibiotics such as erythromycin, rifampicin,

•    chloroquine or mefloquine (for malaria). Taking these with Sodium Valproate may increase the chance of a fit. Before travelling to a malaria area, ask your doctor or pharmacist about the best malaria prevention tablets for you

•    cimetidine (for the treatment of stomach ulcers) or colestyramine (to treat high levels of fat in the blood)

•    carbapenem agents (antibiotic used to treat bacterial infection) such as imipenem, meropenem, rifampicin and erythromycin. The combination of valproic acid and carbapenems should be avoided because it may decrease the effect of Sodium Valproate

•    drugs that prevent blood clotting such as aspirin or warfarin

•    zidovudine (used to treat HIV and AIDS)

•    temozolomide (used to treat cancer).

Sodium Valproate with food, drink and alcohol

Alcohol intake is not recommended during treatment.

Take Sodium Valproate Tablets with or after food. This will help to stop the feelings of sickness that may happen after taking the tablets.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Before you start taking Sodium Valproate, your doctor should discuss with you the possible problems when it is taken in pregnancy.

•    unplanned pregnancy is not desirable in women receiving Sodium Valproate

•    you should not take this medicine if you are pregnant or a women of child-bearing age unless explicitly advised by your doctor. If you are a woman of child-bearing age, you have to use effective contraception during treatment. Sodium Valproate has no effect on how well the oral contraceptive pill works.

Women taking Sodium Valproate during pregnancy have a higher risk than other women of having a child with an abnormality. The chance of abnormalities is increased if you are also taking other antiepileptic medicines at the same time. It can cause serious birth defects and can affect the way in which the child develops as it grows; these abnormalities include:

•    head and face deformities including cleft palate, a gap or depression in the lip

•    malformations of the arms and legs

•    deformities of the bones, including hip dislocation

•    deformities of the tube from the bladder to the penis where the opening is formed in a different place

•    heart and blood vessels malformations with heart defects

•    abnormalities in the lining of nerve tubes with holes or protrusions

•    spina bifida (where the bones of the spine are not properly developed).

Women who take Sodium Valproate during pregnancy may be more likely to have a baby with spina bifida. This is an abnormality of the spinal cord. Taking folic acid 5mg each day as soon as you stop contraception may lower the risk of having a baby with spina bifida.

There is also an increased risk of other birth defects. These other defects can usually be detected in the first 3 months of the pregnancy using routine antenatal screening blood tests and ultrasound scans.

Pregnant mothers who take Sodium Valproate may have babies with blood clotting problems (such as blood not clotting or not clotting very well). This may appear as bruising or a bleeding which takes a long time to stop.

Some babies born to mothers who took Sodium Valproate during pregnancy may develop less quickly than normal. These children may require additional educational support.

Talk to your doctor before stopping taking Sodium Valproate if you want to become pregnant. It is important not to stop your Sodium Valproate suddenly, as it is likely that your fits will come back.

Women who are planning to get Pregnant

If you become pregnant, think you may be pregnant or plan to become pregnant while taking Sodium Valproate, you must tell your doctor straight away.

•    Your doctor will give you appropriate counselling and will suggest changes to your treatment or dose

•    He or she will also want to check your progress while you are pregnant.

It is very important that you discuss your treatment with your doctor well before you become pregnant.

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 or pharmacist for advice before taking any medicine.

Important advice for women

•    Valproate can be harmful to unborn children when taken by a woman during pregnancy.

•    Valproate carries a risk if taken during pregnancy. The higher the dose, the higher the risks but all doses carry a risk.

•    It can cause serious birth defects and can affect the way in which the child develops as it grows. Birth defects which have been reported include spina bifida (where the bones of the spine are not properly developed); facial and skull malformations; heart, kidney, urinary tract and sexual organ malformations; limb defects.

•    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 who don’t have epilepsy.

•    It is estimated that up to 30-40% of preschool children whose mothers took valproate during pregnancy may have problems with early childhood development. Children affected can be slow to walk and talk , intellectually less able than other children, and have difficulty with language and memory.

•    Autistic spectrum disorders are more often diagnosed in children exposed to valproate and there is some evidence children may be more likely to develop symptoms of Attention Deficit Hyperactivity Disorder (ADHD).

•    If you are a woman capable of becoming pregnant your doctor should only prescribe valproate for you if nothing else works for you.

•    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 until you have discussed this with your doctor and agreed a plan for switching you onto another product if this is possible.

•    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.

FIRST PRESCRIPTION

If this is the first time you have been prescribed valproate your doctor will have explained the risks to an unborn child if you become pregnant. Once you are of childbearing age, you will need to make sure you use an effective method of contraception throughout your treatment. Talk to your doctor or family planning clinic if you need advice on contraception.

Key messages:

•    Make sure you are using an effective method of contraception.

•    Tell your doctor at once if you are pregnant or think you might be pregnant.

CONTINUING TREATMENT AND NOT TRYING FOR A BABY If you are continuing treatment with valproate but you don’t plan to have a baby make sure you are using an effective method of contraception. Talk to your doctor or family planning clinic if you need advice on contraception.

Key messages:

•    Make sure you are using an effective method of contraception

•    Tell your doctor at once if you are pregnant or think you might be pregnant.

CONTINUING TREATMENT AND CONSIDERING TRYING FOR A BABY

If you are continuing treatment with valproate and you are now thinking of trying for a baby you must not stop taking either your valproate or your contraceptive medicine until you have discussed this with your prescriber. You should talk to your doctor well before you become pregnant so that you 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 doctor may decide to change the dose of valproate or switch you to another medicine before you start trying for a baby.

If you do become pregnant you will be monitored very closely both for the management of your underlying condition and to check how your unborn child is developing.

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 it unlikely that it will reduce the risk of birth defects associated with valproate use.

Key messages:

•    Do not stop using your contraception before you have talked to your doctor and worked together on a plan to ensure your epilepsy/bipolar disorder is controlled and the risks to your baby are reduced.

•    Tell your doctor at once when you know or think you might be pregnant.

UNPLANNED PREGNANCY WHILST CONTINUING TREATMENT

Babies born to mothers who have been on valproate are at serious risk of birth defects and problems with development which can be seriously debilitating. If you are taking valproate and you think you are pregnant or might be pregnant contact your doctor at once. Do not stop taking your medicine until your doctor tells you to.

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:

•    Tell your doctor at once if you know you are pregnant or think you might be pregnant.

•    Do not stop taking valproate unless your doctor tells you to.

Make sure you read the patient booklet and sign the Acknowledgement of Risk form which should be given to you and discussed with you by your doctor or pharmacist.

Driving and using machines

You may feel sleepy:

•    when you first start taking Sodium Valproate

•    if you are taking it with other medicines, such as other antiepileptic drugs or benzodiazepines.

If this happens to you, do not drive or use any tools or machines.

3. How to take Sodium Valproate

Sodium Valproate treatment must be started and supervised by a doctor specialised in the treatment of epilepsy or bipolar disorders. Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

These tablets have been coated with a substance that will allow them to pass through the stomach before dissolving.

The tablets should be swallowed preferably with a drink of water usually after meals. These tablets should not be chewed or crushed.

The recommended dose is:

•    Adults

Initially 600 mg daily, increasing by 200 mg at three-day intervals until control of fits is achieved. This may be increased up to a maximum of 2500 mg per day. This quantity may be given in one dose or can be divided and taken in two separate doses e.g. half in the morning and half in the evening.

•    Children over 20 kg

Initially 400 mg daily. The doctor will adjust the dose of Sodium Valproate for your child based on the child’s body weight until control of fits is achieved. This quantity may be given in one dose or can be divided and given in two separate doses e.g. half in the morning and half in the evening.

•    Children under 20 kg

The doctor will calculate the appropriate dose of Sodium Valproate for your child based on the child’s body weight.

•    Older people and patients with kidney problems

Your doctor will decide a suitable dose to achieve adequate control of your epilepsy.

When treatment is first started, you may be prescribed a lower dose. This is because some patients need less Sodium Valproate than others to control their fits. Your doctor will increase the dosage until your condition is controlled. Because of this, it is very important that you follow the instructions your doctor has given you about how much to take.

Mania

The daily dosage should be established and controlled individually by your doctor.

Initial dose

•    The recommended initial daily dose is 750 mg.

Mean daily dose

•    The recommended daily doses usually range between 1000 mg and 2000 mg.

Taking Sodium Valproate together with another therapy:

You may be taking other drugs to control your epilepsy at the same time as Sodium Valproate. If you are, your doctor may increase the dose of Sodium Valproate.

If you take more Sodium Valproate than you should

If you (or someone else) swallow a lot of the tablets all together or if you think a child has swallowed any of the tablets, contact your nearest hospital casualty department or your doctor immediately.

An overdose is likely to cause nausea, vomiting, dizziness, and difficulty breathing.

Please take this leaflet, any remaining tablets, and the container with you to the hospital or doctor so that they know which tablets were consumed.

If you forget to take Sodium Valproate

If you forget to take your tablets, take them as soon as you remember, unless it is nearly time to take the next dose. Do not take a double dose to make up for a forgotten dose.

If you stop taking Sodium Valproate

DO NOT stop taking Sodium Valproate or change the number of tablets you are taking without first discussing this with your doctor, as this may lead to a recurrence of your symptoms.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them. Serious side effects

Stop taking the tablets and tell your doctor immediately or go to the casualty department at your nearest hospital if any of the following happens:

•    an allergic reaction causing swelling of the lips, face, throat, neck or tongue leading to severe difficulty in swallowing or breathing. Hands, feet or genitals may also be affected.Severe skin rash or hives joint pain, fever (systemic lupus erythematosus). More severe allergic reactions can lead to lymph node enlargement and possible impairment of other organs.

•    Liver problems and problems of the pancreas (e.g inflammation of the pancreas) may show as a sudden illness, especially if it is within the first six months of treatment, particularly if it includes repeated vomiting, extreme tiredness, abdominal pain, drowsiness, weakness, loss of appetite, severe upper stomach pains, nausea, jaundice (yellowing of the skin or whites of the eyes), swelling of the legs, worsening of your condition or a general feeling of being unwell.

If you have some of these symptoms, they may be signs of problems with your liver or pancreas

•    You have a skin rash or skin lesions with a pink/red ring and a pale centre which may be itchy, scaly or filled with fluid. The rash may appear especially on the palms or soles of your feet. These could be signs of a serious allergy to the medicine called ‘erythema multiforme’

•    Blistering or bleeding of the skin around the lips, eyes, mouth, nose and genitals. Also flu-like symptoms and fever. This may be something called ‘Stevens-Johnson syndrome’

•    Severe blistering rash where layers of the skin may peel off to leave large areas of raw exposed skin over the body. Also a feeling of being generally unwell, fever, chills and aching muscles. This may be something called ‘Toxic epidermal necrolysis’

•    Bruising more easily and getting more infections than usual. This could be a blood problem called ‘thrombocytopenia’. It can also be due to a fall in the number of white blood cells, bone marrow (osteopenia and osteoporosis - thinning of the bone - and fractures. Check with your doctor or pharmacist if you are on long-term antiepileptic medication, have a history of osteoporosis, or take steroids.) depression or another condition that affects red blood cells, white blood cells and platelets (pancytopenia) or how the blood clots

•    Blood clotting problems (bleeding for longer than normal), bruising or bleeding for no reason

•    Changes in mood, loss of memory, lack of concentration and deep loss of consciousness (coma)

•    Underactive thyroid gland, which may cause tiredness or weight gain (hypothyroidism)

•    Breathing difficulty and pain due to inflammation of the lungs (pleural effusion)

•    Birth defects

These are very serious but rare side effects. You may need urgent medical attention or hospitalisation.

Other side effects

Tell your doctor as soon as possible if you experience any of the following effects or if you get any unusual symptoms, as you may have to stop taking the tablets:

Very common: may affect more than 1 in 10 people

•    tremor

•    feeling unwell (nausea)

Common: may affect up to 1 in 10 people

•    decrease in blood sodium, which may be identified by the following common symptoms: dehydration including fatigue, weakness, cramp, nausea, vomiting, bloating, swelling, and tightness of the hands and feet, dizziness, confusion, fainting or seizures. Less commonly you may be bloated with swelling and tightness of the hands and feet, feel confused and have fits. Sometimes it can cause changes in the blood. Here you may notice unusual bleeding or bruising more easily, severe stomach pains, feeling shaky or problems with balance.

•    tiredness, confusion, disturbance in attention, hallucinations, change in mood, loss of consciousness, aggression, agitation.

•    extrapyramidal disorders, the symptoms may include feeling shaky (tremor), or unsteady when walking or jerky muscle movements

•    hearing problems or hearing loss

•    stomach ache, or diarrhoea - especially for the first few days after starting the treatment

•    nail and nail bed disorders

•    loss of hair; this is usually temporary but when it grows back it may be more curly than before

•    painful periods in women

•    weight gain, as your appetite may be increased

Uncommon: may affect up to 1 in 100 people

•    neurological problems including reversible parkinsonism (feeling shaky)

•    changes in periods in women (irregular)

•    swelling of the feet and legs (oedema)

Rare: may affect up to 1 in 1,000 people

•    suicidal thoughts or other changes in your behaviour including feeling very alert may occur, sometimes with aggression, hyperactivity, and behavioural deterioration. This can be associated with more frequent or severe fits, loss of drive, particularly if phenobarbital is taken at the same time, or if your Sodium Valproate dose has been suddenly increased

•    Obesity

•    changes in the amount of ammonia in the blood; symptoms of this may include drowsiness, being sick, or difficulties with balance and co-ordination such as unsteadiness when walking

•    abnormal behaviour, restlessness/hyperactivity and learning disorder

•    neurological problems including reversible dementia

•    sleepy (sedation)

•    kidney problems, bedwetting or increased need to pass urine

•    skin reactions such as rashes occur rarely, but patients who are also taking lamotrigine may be more at risk

•

Very rare: may affect up to 1 in 10,000 people

•    acne

•    increased hair growth in women; hair, including body or facial hair grows more than normal

•    increased breast growth in men

Not known: frequency cannot be estimated from the available data

•    vasculitis (inflammation of the blood vessels) - you may notice pain, redness or itching

•    being sick

These effects usually get better when you stop taking Sodium Valproate tablets.

Reporting of side effects

If you get any side effects, talk to your doctor 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.

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 store above 30°C. Store in the original package.

Do not use this medicine after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.

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 to protect the environment.

6.    Contents of the pack and other information

What Sodium Valproate Teva Gastro-resistant Tablets contain

•    Sodium Valproate Gastro-resistant Tablets contain either 200 mg or 500 mg of Sodium Valproate.

•    The other ingredients are povidone (E1201), talc, magnesium stearate (E572), calcium silicate, polyvinyl acetate, polyvinyl acetate phthalate, citric acid anhydrous, hypromellose, macrogol 6000, violet lake solids, diethyl phthalate, and stearic acid.

What Sodium Valproate Gastro-resistant Tablets look like and contents of the pack

•    Sodium Valproate Teva 200 mg Gastro-resistant Tablets are round lilac biconvex gastro-resistant tablets.

•    Sodium Valproate Teva 500 mg Gastro-resistant Tablets are round lilac biconvex gastro-resistant tablets.

•    Sodium Valproate Teva Gastro-resistant Tablets are available in packs of 100 and 112 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation holder: TEVA UK Limited, Eastbourne, BN22 9AG.

The company responsible for manufacture is Sterwin Medicines, Fawdon Manufacturing Centre, Fawdon, Newcastle Upon Tyne, England.

This leaflet was last revised in April 2016

PL 00289/0324-0325

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