504096/PL1c

Epilim® Chronosphere® 100 mg Modified Release Granules

(sodium valproate & valproic acid)

Patient Information Leaflet

^^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.

What is in this leaflet

1.    What Epilim Chronosphere is and what it is used for

2.    What you need to know before you take Epilim Chronosphere

3.    How to take Epilim Chronosphere

4.    Possible side effects

5.    How to store Epilim Chronosphere

6.    Contents of the pack and other information

1) WHAT EPILIM CHRONOSPHERE IS AND WHAT IT IS| USED FOR

What Epilim Chronosphere is

The name of your medicine is Epilim Chronosphere 100 mg Modified Release Granules, (called Epilim Chronosphere in this leaflet. Other strengths are available). “Modified release” means that the active ingredients (sodium valproate and valproic acid) are slowly released from the granules over a long period of time.

What Epilim Chronosphere contains

Epilim Chronosphere contains two medicines called sodium valproate and valproic acid. Both belong to a group of medicines called anti-convulsants or anti-epileptic agents. They work by helping to calm the brain down.

What Epilim Chronosphere is used for

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

2) WHAT YOU NEED TO KNOW BEFORE YOU TAKE| EPILIM CHRONOSPHERE

Do not take Epilim Chronosphere and tell your doctor if:

•    You are allergic (hypersensitive) to sodium valproate, valproic acid or any of the other ingredients of Epilim Chronosphere (listed in Section 6 below).

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

•    You have a rare illness called porphyria

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

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Epilim Chronosphere.

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 Epilim Chronosphere if:

•    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 a 'urea cycle disorder' - where too much ammonia builds up in the body.

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

•    You know that there is a genetic problem caused by a mitochondrial disorder in your family

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Epilim Chronosphere

Weight gain

Taking Epilim Chronosphere 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 taking Epilim Chronosphere and during your treatment.

Other medicines and Epilim Chronosphere

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Epilim Chronosphere can affect the way some other medicines work. Also some medicines can affect the way Epilim Chronosphere works.

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

•    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

Epilim Chronosphere 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 Epilim Chronosphere 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 Epilim Chronosphere and carbapenems should be avoided because it may decrease the effect of your medicine.

•    Colestyramine used to lower blood fat (cholesterol) levels

Taking Epilim Chronosphere 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.

Breast-feeding

Very little Epilim Chronosphere 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.

Driving and using machines:

You may feel sleepy when taking Epilim Chronosphere. 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 problems may increase sleepiness.

Always take Epilim Chronosphere exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Epilim Chronosphere treatment must be started and supervised by a doctor specialised in the treatment of epilepsy.

Taking this medicine

•    Your doctor will decide how much Epilim Chronosphere to give you or your child depending on your or your child's body weight

•    Take this medicine by mouth

•    Do not crush or chew the granules

•    Do not store partially used sachets or a mixture of the granules with liquid or food for future use. Always use the full contents of each sachet

•    Do not sprinkle Epilim Chronosphere on warm or hot foods and drinks, such as soup, coffee, tea, or something similar

•    The granules should not be given in babies bottles. This is because they can block the nipple

•    If you feel the effect of your medicine is too weak or too

strong, do not change the dose yourself but ask your ^doctor    Continued overleaf

How to take this medicine

•    This medicine can be taken once or twice daily

•    The granules should be sprinkled on a small amount of soft food or drink which should be cold or at room temperature

•    This medicine can be taken with soft food or drink such as yoghurt, mousse, jam, ice cream, milk shake and orange juice

•    When the granules are put onto food, you must swallow all the food with the granules to make sure you get the correct dose of medicine

•    When the granules are swallowed in a drink, the empty glass should be rinsed with a small amount of water. This water should be swallowed because some granules may stick to the glass

•    The mixture of granules with food or drink should be swallowed immediately

How much to take Adults

•    The starting dose is 600 mg daily. Your doctor will gradually increase this dose by 200 mg every 3 days depending on your condition

•    The usual dose is generally between 1000 mg and 2000 mg (20-30 mg per kilogram of body weight) each day

•    This may be increased to 2500 mg each day depending on your illness

Children over 20 kilograms

•    The starting dose should be 400 mg daily. Your doctor should increase this dose depending on your child's illness

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

•    This may be increased to 35 mg for each kilogram of body weight each day depending on your child's illness

Children under 20 kilograms

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

•    Depending on the child's condition your child's doctor may decide to increase this dose

Patients with kidney problems

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

Patients taking other medicines for ‘fits' (epilepsy)

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

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

If you take more Epilim Chronosphere than you should

If you take more Epilim Chronosphere than you should, tell a doctor or go to a hospital casualty department straight away. Take the medicine pack with you. This is so the doctor knows what you have taken. The following effects may happen: feeling sick or being sick, pupils of the eye become smaller, dizziness, loss of consciousness, weak muscles, breathing problems, headaches, memory loss and unusual or inappropriate behaviour.

If you forget to take Epilim Chronosphere

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

If you stop taking Epilim Chronosphere

Keep taking until your doctor tells you to stop. Do not stop taking Epilim Chronosphere just because you feel better. 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. Epilim Chronosphere 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 Epilim Chronosphere.

You may see what appears to be complete granules in your stool. This is normal as the matrix of the Epilim Chronosphere granules is not digested by the body. It does not mean that the medicine is not working.

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

Like all medicines, Epilim Chronosphere 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 Epilim Chronosphere. 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 Epilim Chronosphere 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 Epilim Chronosphere starting dose is high or has been suddenly increased

•    High levels 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. Feeling sick may be made better by taking the granules with food

•    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 in the hands and 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

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

Male Fertility

Taking Epilim Chronosphere can be a contributing factor in male infertility.

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 at: www.mhra.gov.uk/vellowcard.

By reporting side effects, you can help provide more information on the safety of this medicine.

•    Keep out of the sight and reach of children.

•    Do not take this medicine after the expiry date shown on the sachet and the pack after EXP The expiry date refers to the last day of that month.

•    Do not store above 25°C.

•    Store in the original packaging.

•    Do not refrigerate or freeze.

•    Medicines should not be disposed of via household wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

•    If the sachets become discoloured or show signs of any deterioration, consult your doctor or pharmacist who will tell you what to do.

What Epilim Chronosphere contains

•    Each sachet contains a mixture of 66.66 mg sodium valproate and 29.03 mg valproic acid, equivalent to 100 mg of the active substance sodium valproate

•    The other ingredients are paraffin hard, glycerol dibehenate and silica colloidal hydrated.

What Epilim Chronosphere looks like and contents of the pack

•    The sachets contain small off-white to slightly yellow, waxy microgranules.

•    These modified release granules are supplied in cartons of 30 sachets.

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

Product Licence Holder

Procured from within the EU. Product Licence Holder Ginova Ltd, repackager Ginova UK Ltd, both of St James' House, 8 Overcliffe, Gravesend, Kent, DA11 0HJ.

Manufacturer

Sanofi Winthrop Industrie, 196 Rue du Marechal Juin, Amilly, F-45200, France.

Epilim® Chronosphere®    100 mg

Granules

PL No: 18067/0412

Epilim® and Chronosphere® are registered trademarks.

This leaflet was last approved on 7^th May 2015.

There are two organisations that will also be happy to try and answer any general questions on epilepsy. They can be contacted at:

Epilepsy Action, New Anstey House, Gate Way Drive, Yeadon, Leeds, LS19 7XY

Telephone: 0808 800 5050. Website: www.epilepsy.org.uk

National Society for Epilepsy (NSE), Chesham Lane, Chalfont St Peter, Bucks, SL9 0RJ Telephone: 01494 601400.

Website: www.epilepsynse.org.uk

Epilepsy Action and The National Society for Epilepsy (NSE) are not associated with Ginova Ltd or Ginova UK Ltd.

To request a copy of this leaflet in Braille, large print or audio please call 01622 690172.

504096/PL1c