THE NAME OF YOUR MEDICINE IS EPISENTA® SOLUTION FOR INJECTION (SODIUM VALPROATE)

Episenta® solution for injection is a ready-to-inject solution for injection.
The solution contains the active ingredient sodium valproate.

Other ingredients include:
Disodium edetate and water for injections

One glass ampoule contains 3 ml or 10 ml solution for injection.

Each pack contains 5 ampoules of 3 ml solution for injection or 5 ampoules of 10 ml solution for injection.

The active ingredient belongs to a group of medicines known as anticonvulsants which are used in the treatment of epilepsy (fits).

The Product Licence holder is Beacon Pharmaceuticals Ltd, 85, High Street, Tunbridge Wells, Kent TN1 1YG, UK.

The product is manufactured by Desitin Arzneimittel GmbH, Weg beim Jäger 214, D-22335 Hamburg, Germany.

WHAT IS EPISENTA® SOLUTION FOR INJECTION FOR?

Episenta® solution for injection (sodium valproate) is used in the treatment of various types of epilepsy when sodium valproate cannot be given by mouth.

BEFORE TAKING THIS MEDICINE.

You should not take Episenta® solution for injection if

• you have been told that you are allergic to sodium valproate or other constituents of the product
• you have liver disease
• severe hepatic (liver) dysfunction, particularly caused by drugs, is known in your family
• you suffer from an hereditary or acquired disease called porphyria (disturbance in metabolism of red blood pigment)

You should tell your doctor if you are pregnant or intend to become pregnant or wish to start breast feeding whilst you are treated with this drug. It may cause abnormalities in the baby and therefore special monitoring tests are usually required during pregnancy.
You may need to have periodic blood tests to check your levels of sodium valproate and to check for blood or liver problems. 

You will need to discuss with your doctor whether you should drive or operate machinery, which will depend on how well your disease is controlled and whether Episenta® solution for injection makes you drowsy.

Problems may occur when Episenta® solution for injection is administered in combination with other medicines including some other anticonvulsant drugs (e.g. phenytoin, carbamazepine, phenobarbitone, lamotrigine), mefloquine (drug used to treat malaria), cimetidine (anti-ulcer drug), erythromycin (antibiotic), cholestyramine (used to reduce the level of blood lipids [fats]), zidovudine (drug to treat HIV (AIDS)), aspirin and agents which are used to thin the blood (e.g. warfarin) and some drugs for mental illness, including depression. This warning may also apply to medicines you can buy without a prescription. Sodium valproate can affect the results of some urine tests in diabetics. It may be necessary to alter the dose of Episenta® solution for injection or the other medicine.

Alcohol can increase the interference in liver function by sodium valproate. You should therefore avoid alcohol.

Make sure your doctor knows what other medicines you are taking, including those you can buy from a pharmacy without a prescription.

If you have any doubts about whether you should be given this medicine, then you should discuss things more fully with your doctor BEFORE taking them.

TAKING THIS MEDICINE.

Your doctor will decide which dose is best for you.  Always follow your doctor's instructions completely and also follow any special instructions or warnings which appear on the label which the pharmacist has put on the pack.  If you do not understand, or are in any doubt ask your doctor or pharmacist.

The dose you need depends on your age and body weight and will be adjusted individually to achieve adequate control of your fits. Episenta® solution for injection is ready for intravenous injection.  If you have been taking sodium valproate already by mouth, the dose given to you will be the same by injection.

The intravenous administration of Episenta® solution for injection should be replaced by oral therapy as soon as practicable.

Blood samples may need to be taken during treatment with Episenta® solution for injection in order to monitor blood levels of the drug.

The total daily dose should be divided into three to four single slow intravenous injections or should be given by continuous infusion.

The usual adult starting dose is 400 - 800mg (4 – 8 ml) daily increased by 150-300mg (1,5 – 3,0 ml) at three day intervals until control of fits is achieved. The maximum dose is 2,500mg per day. Elderly patients and patients with reduced kidney function may need lower doses. Your doctor may also adjust your dose if you are taking other antiepileptic drugs. The dose for children will depend on their weight. This is usually 20-40 mg per kg of body weight. Your doctor will decide which dose is best for you.

Method of administration
Episenta® solution for injection may be given by slow intravenous injection over 3-5 minutes or by infusion in 0.9% saline or 5% dextrose.

Prior to use Episenta® solution for injection and the diluted solution should be visually inspected. Only clear solutions without particles should be used.

AFTER TAKING THIS MEDICINE.

In common with many medicines Episenta® solution for injection may cause side-effects in some patients, particularly when treatment is first started.

Sodium valproate very commonly causes weight gain.

Liver problems, even severe liver damage and disorders in the production of blood cells such as leucopenia [reduction of white blood cells], red cell hypoplasia [disturbed production of red blood cells], thrombocytopenia [reduction of blood platelets], pancytopenia [reduction of all blood cells] can occur, which is another reason for regular blood tests. Sodium valproate can also disturb blood coagulation, which might cause prolonged bleeding in case of injury.

In some cases, laboratory examination of the blood might show changes in the tests for liver function, pancreatic function, blood clotting or blood count.

Minor gastric irritation like nausea, vomiting and alterations in appetite may occur in rare cases at the start of treatment.

An isolated and moderately pronounced increase in ammonia levels (hyperammonaemia) can often occur, without any change in liver function parameters, and does not require treatment to be stopped. However, it may cause clinical signs such as vomiting, ataxia and increasing clouding of consciousness. Should these symptoms occur Episentaâ solution for injection should be discontinued.

An accumulation of tissue fluid (oedema) has been reported rarely. Damage to the pancreas, which was sometimes fatal, has been reported in isolated cases. If you experience symptoms like abdominal pain, nausea and vomiting consult your doctor immediately.

Unsteadiness of gait (ataxia), trembling (tremor) and sedation have been reported occasionally.

Rare cases of lethargy and confusion occasionally progressing to stupor, sometimes with associated hallucinations or convulsions have been reported.

Coma has very rarely been observed. These cases have often been associated with too high a starting dose, too rapid an increase in dose or the simultaneous use of other anticonvulsants. It has usually been reversible on withdrawal of treatment or reduction of dosage.

An increase in alertness may occur. Occasionally aggression, hyperactivity and behavioural deterioration have been reported.

Hearing loss, either reversible or irreversible has rarely been reported, though it is not certain that it was caused by sodium valproate.

Increase in appetite and an increase in weight is not uncommon.

Temporary hair loss with regrowth of curly hair has been noted in some patients. Rashes have rarely been reported.

There have been isolated reports of irregular periods or absence of menses (amenorrhoea), acne and increased hairiness in woman (hirsutism). Very rarely, enlargement of the breasts in men (gynaecomastia) has occurred.

In individual cases, sodium valproate led to changes in immune defence mechanisms (vasculitis, lupus erythematosus-like symptoms).

If you suddenly become ill with vomiting, weakness, drowsiness, loss of appetite, unsteadiness and possibly jaundice (yellow skin), or if your fits occur more often tell your doctor immediately.

If you experience any other side-effects or think that you may be reacting badly in any way, tell your doctor or pharmacist. 

Sodium valproate and pregnancy
It is essential that you discuss your epilepsy treatment with your doctor well before you intend to become pregnant. Women who take sodium valproate during the first month of pregnancy to control their epilepsy have a small risk (1-2%) of having a baby with spina bifida, an abnormality of the spinal cord. There is also an increased risk of other congenital abnormalities. These can usually be detected in the first part of pregnancy by normally used screening tests. Taking folic acid 5 mg daily as soon as you stop contraception may lower the risk of having a baby with spina bifida. Rarely there may also be clotting problems in the new born if the mother has taken sodium valproate during pregnancy. Infants born to mothers who took sodium valproate during pregnancy may develop less quickly than normal. This may also be because of the mother’s epilepsy but the exact cause is not known. It is important not to stop your sodium valproate suddenly as this may result in fits, which may harm you or your unborn baby.

If too much Episenta® solution for injection has been administered contact your doctor or nearest hospital casualty department. Take this leaflet to show the doctor.

Cases of accidental and suicidal overdosage with oral therapy have been reported. At plasma concentrations of up to 5 to 6 times the maximum therapeutic levels, there are unlikely to be any symptoms other than nausea, vomiting and dizziness. After massive overdose there may be serious CNS depression and respiration may be impaired. In some cases the outcome can be even fatal.

Hospital management of overdose including induced vomiting, gastric lavage, assisted ventilation and other supportive measures is recommended. Haemodialysis and haemoperfusion have been used successfully.

June 2006