Package leaflet: Information for the user

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

Sodium Valproate

T This 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.

WARNING

Valproate can cause birth defects and problems with early development of the child if it is taken during pregnancy. If you are a female of childbearing age you should use an effective method of contraception throughout your treatment.

Your doctor will discuss this with you but you should also follow the advice in section 2 of this leaflet. Tell your doctor at once if you become pregnant or think you might be pregnant.

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 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.

The name of your medicine is Sodium Valproate 400mg Powder and Solvent for solution for injection/infusion.

In the rest of this leaflet this medicine will be called Sodium Valproate.

What is in this leaflet

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

2.    What you need to know before you are    given

Sodium Valproate

3.    How Sodium Valproate is given

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

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.

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

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

Do not have Sodium Valproate and tell your doctor or nurse 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.

•    You have liver problems or you or your family have a history of liver problems.

•    If you have a genetic problem caused by a mitochondrial disorder (e.g. Alpers-Huttenlocher syndrome).

Do not have this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before having Sodium Valproate.

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:

•    You have diabetes. This medicine may affect the

results of urine tests.

•    You have kidney problems. Your doctor may give

you a lower dose.

•    You have fits (epilepsy), brain disease or a

metabolic condition affecting your brain.

•    You have a ‘urea cycle disorder' where too much

ammonia builds up in the body.

•    You have an illness called “systemic lupus erythematosus (SLE)” - a disease of the immune system which affects skin, bones, joints and internal organs.

•    You know that there is a genetic problem caused

by a mitochondrial disorder in your family.

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

Weight gain

Having 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 having Sodium Valproate and during your treatment.

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.

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

•    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, topiramate, lamotrigine and felbamate.

Sodium Valproate may increase the effect of the following medicines:

•    Medicines used for thinning the blood (such as warfarin).

•    Zidovudine used to treat HIV infection.

•    Temozolomide used to treat cancer.

•    Medicines for depression.

•    Monoamine oxidase inhibitors (MAOI) such as moclobemide, selegiline, linezolid.

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

The following medicines can affect the way Sodium Valproate works:

•    Some medicines used for the prevention and treatment of malaria such as mefloquine and chloroquine.

•    Cimetidine used for stomach ulcers.

•    Carbapenem agents (antibiotics used to treat bacterial infections) such as imipenem, meropenem, rifampicin and erythromycin. The combination of Sodium Valproate and carbapenems should be avoided because it may decrease the effect of your medicine.

•    Colestyramine used to lower blood fat (cholesterol) levels.

Sodium Valproate with food and drink

Alcohol intake is not recommended during treatment.

Pregnancy, breast-feeding and fertility 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 every 100 born to women who don't have epilepsy.

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

•    Autistic spectrum disorders are more often diagnosed in children exposed to valproate 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 is 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 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.

Breastfeeding

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 or having any medicine.

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.

Important information about some of the ingredients of Sodium Valproate

This medicinal product contains approximately 55mg sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

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 between 400mg and 800mg (up to 10mg per kilogram of body weight).

•    This is given as a slow intravenous injection over 3-5 minutes.

This is followed by a continuous or repeated infusion, up to a maximum of 2500mg each day.

Children

•    The usual dose is between 20mg and 30mg for each kilogram of body weight each day.

•    This may be increased to 40mg for each kilogram of body weight each day depending on your child's illness.

Patients with kidney problems

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

Patients taking other medicines for ‘fits’ (epilepsy)

•    You or your child may be taking other medicines for epilepsy at the same time as Sodium Valproate. If so, your doctor should gradually initiate treatment depending on you or your child’s condition.

•    Your doctor may increase the dose of Sodium Valproate by 5 to 10mg for each kilogram of body weight each day depending on which other medicines you are taking.

If you are given 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.

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

If you forget to be given 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 doctor decides to stop them. If you stop, your fits may come back.

Tests

Make sure you or your child keep your regular appointments for a check up.

They are very important as your or your child's dose may need to be changed.

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.

If you or your child go into hospital or visit another doctor or a dentist, tell them you are taking Sodium Valproate.

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.

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

•    You have an allergic reaction. The signs may include: a rash, joint pain, fever (systemic lupus erythematosus), swallowing or breathing problems, swelling of your lips, face, throat or tongue. Hands, feet or genitals may also be affected. More severe allergic reactions can lead to lymph node enlargement and possible impairment of other organs.

•    Liver problems and problems of the pancreas may show as a sudden illness which may happen in the first six months of treatment. This happens in a very small number of people taking Sodium Valproate. 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 Sodium Valproate immediately if you have these symptoms.

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

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

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

•    Bruising more easily and getting more infections than usual. This could be a blood problem called ‘thrombocytopenia'. It can also be due to a fall in the number of white blood cells, bone marrow depression or another condition that affects red blood cells, white blood cells and platelets (pancytopenia) or how the blood clots.

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

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

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

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

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

•    Changes in behaviour including being very alert, and sometimes also aggressive, hyper-active and unusual or inappropriate behaviour. This is more likely if other medicine to treat fits such as phenobarbital and topiramate are taken at the same time or if the Sodium Valproate starting dose is high or has been suddenly increased.

•    Changes in the amount of ammonia in the blood. Symptoms of this condition are being sick, problems with balance and co-ordination, feeling lethargic or less alert.

•    Feeling shaky (tremor), sleepy or unsteady when walking or jerky muscle movements.

•    Feeling tired or confused with loss of consciousness sometimes accompanied by hallucinations or fits.

•    Blisters with the skin flaking away.

•    Rapid, uncontrollable movement of the eyes.

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, stomach ache or diarrhoea, especially when starting treatment.

•    Fainting.

•    Hearing loss.

•    Skin problems such as rashes. These happen rarely, but more often in people also taking lamotrigine.

•    Acne.

•    Hair loss which is usually temporary. When it grows back it may be more curly than before

•    Hair, including body or facial hair grows more than normal in women.

•    Skin rash caused by narrow or blocked blood vessels (vasculitis).

•    Changes in women's periods and increased hair growth in women.

•    Breast enlargement in men.

•    Swelling of the feet and legs (oedema).

•    Weight gain - as your appetite may be increased.

•    Kidney problems, bedwetting or increased need to pass urine.

•    Headache.

•    Aggression, agitation, disturbance in attention., abnormal behaviour, restlessness/hyperactivity and learning disorder

•    Tingling or numbness of the hands or feet Bone Disorders

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 antiepileptic medication, have a history of osteoporosis, or take steroids.

Blood tests

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

Male Fertility

Sodium Valproate can be a contributing factor in male infertility.

Talk to your doctor or pharmacist if any of the side effects get serious or lasts longer than a few days, or if you notice any side effects not listed in this leaflet.

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 Yellow Card Scheme, Website: 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 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.

Do not use this medicine if you notice any particles.

This medicinal product does not require any special storage conditions.

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 400mg of the active substance, sodium valproate.

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., 21st km National Road Athens-Lamia, 14568 Krioneri, Athens, Greece.

This medicinal product is authorised in the Member States of the EEA under the following names:

United Kingdom: Sodium Valproate 400 mg Powder and Solvent for solution for injection/infusion

This leaflet was last revised in 09/2015.

If this leaflet is difficult to see or read, please contact the following address for help:

Athlone Laboratories, Ballymurray, Co. Roscommon, Ireland,

Tel +353-9066-61109,

Email medical@athlone-laboratories.com.