How does it work?

Episenta prolonged-release capsules, prolonged-release granules and injection all contain the active ingredient sodium valproate, which is a medicinethat is used mainly to treat epilepsy. Sodium valproate is also availablewithout a brand name, ie as thegeneric medicine. Sodium valproate works by stabilisingelectrical activity in the brain.

The brain and nerves are made up of many nerve cells thatcommunicate with each other through electrical signals. These signals must becarefully regulated for the brain and nerves to function properly. Whenabnormally rapid and repetitive electrical signals are released in the brain,the brain becomes over-stimulated and normal function is disturbed. Thisresults in fits or seizures.

Sodium valproate prevents epileptic fits by preventing theexcessive electrical activity in the brain. It is thought to achieve this byincreasing the activity of a neurotransmitter called GABA in the brain.

Neurotransmitters are chemicals that are stored in nerve cellsand are involved in transmitting messages between the nerve cells. GABA is aneurotransmitter that acts as a natural 'nerve-calming' agent. It helps keepthe nerve activity in the brain in balance.

Sodium valproate is thought to increase the production andprevent the breakdown of GABA in the brain. This increases the calming activityof GABA in the brain, which stabilises the electrical nerve activity and helpsprevent fits.

Sodium valproate may also stabilise the electrical nerveactivity by preventing sodium from entering the nerve cells when they begin tofire rapid and repetitive electrical signals. A build up of sodium in the nervecells is necessary for an electrical signal to build up and be passed on, sosodium valproate may also prevent fits in this way.

In addition to its licensed use for treating epilepsy, sodiumvalproate is used off-licence by specialists as a mood stabiliser for treatingpeople with the psychiatric illness, bipolar affective disorder. This use isnot licensed, but the medicine has been shown to be effective for controllingepisodes of mania in this condition, and for helping prevent future episodes ofill health. It is not fully understood how sodium valproate works as a moodstabiliser in bipolar disorder, but is thought to be to do with the increasedactivity of GABA in the brain.

Episenta capsules and granules are prolonged-release forms of sodium valproate. They aredesigned to release the medicine slowly and continuously over a fewhours to help provide steady blood levels of the medicine throughout the day.

The capsules should be swallowed whole and must not be crushed or chewed, toavoid damaging the prolonged-release action. For people who have difficulty swallowing the capsules, they can be opened and the contents mixed with cold or room temperature food or drink. This should be swallowed immediately without chewing.

Similarly, the granules should be mixed with cold or room temperature food or drink and swallowed immediately without chewing. If the granules are taken in a drink, some granules may stick to the glass after the drink has been finished. For this reason the glass should be rinsed with a small amount of water and this water swallowed as well.

A mixture of the granules with liquid or soft food should not be stored for future use.

What is it used for?

• Epilepsy.
• Treatment of acute manic episodes in bipolar affective disorder.
• As a mood stabiliser in bipolar affective disorder to help prevent episodes of mania in people whose manic episode responded to this medicine.

Warning!

• This medicine may cause drowsiness, especially if it is taken with other antiepileptic medicines, or with benzodiazepines such as lorazepam. This may affect your ability to drive or operate machinery.
• Episenta prolonged-release granules are coated with an indigestible cellulose shell, which allows the sodium valproate to be released slowly. These shells may sometimes be visible as a white residue in the stools. This is normal and nothing to worry about.
• This medicine can cause some people to put on weight. Talk to your doctor about this before you start treatment so that you can discuss strategies, such as diet and exercise, for minimising any weight gain.
• This medicine may on rare occasions affect your liver, pancreas or blood cells. You should have blood tests to monitor your liver function, blood cells and blood clotting time before you start treatment. Your liver function should be monitored for the first six months of treatment, and your blood cell count should be checked before any surgery. Tell your doctor immediately if you, or a child taking this medicine, experience any of the following symptoms during treatment, particularly if they come on suddenly or occur in the first six months of taking the medicine: lack of appetite and energy, weakness, feeling generally unwell, drowsiness, nausea, vomiting, severe abdominal pain, swelling of ankles, yellowing of the skin or whites of the eyes (jaundice), or unusual bruising or bleeding.
• This medicine may cause skin reactions. You should let your doctor know if you develop a rash, skin peeling, itching, or other unexplained skin reaction while taking this medicine.
• There may be a small increased risk of suicidal thoughts and behaviour in people taking antiepileptic medicines such as valproate for any condition. For this reason, it is very important to seek medical advice if you, or someone else taking this medicine, experience any changes in mood, distressing thoughts, or feelings about suicide or self-harm at any point while taking this medicine. For more information speak to your doctor or pharmacist.
• Long-term treatment with valproate may decrease bone mineral density, which could increase the risk of breaking a bone. Your doctor might want you to take vitamin D supplements to avoid this if you are going to be immobilised for a long time, or if you don't get enough sunlight or calcium in your diet.
• People with diabetes should be aware that sodium valproate may cause false positive results in urine tests for ketones, ie the test may say that ketones are present in the urine even if they are not.
• If you have epilepsy it is important to take your medication regularly, as directed by your doctor, because missing doses can trigger seizures in some people. If you have trouble remembering to take your medicine you should ask your pharmacist for advice. You may find a pill reminder box helpful.
• You should not suddenly stop taking this medicine unless your doctor tells you otherwise, as suddenly stopping treatment is likely to make your symptoms return. If this medicine is stopped, it should normally be done gradually, under the supervision of your specialist.
• Wherever possible, it is recommended that people with epilepsy always receive the same brand of their antiepileptic medicine. This is because different brands of these medicines may differ in the way they are absorbed into the body, which could either reduce the effect of the medicine and increase the risk of seizures, or increase the effect of the medicine and hence increase the risk of side effects. You should make sure you know what brand of valproate you normally take and check with your pharmacist if you are ever dispensed a different brand.

Use with caution in

• Young children.
• Decreased kidney function.
• History of liver disease.
• Disorders of urea production in the liver (urea cycle disorders).
• Long-term inflammation of skin and some internal organs (systemic lupus erythematosus).
• Diabetes.

Not to be used in

• Active liver disease.
• Personal or family history of severely decreased liver function, particularly if it is due to a medicine.
• Hereditary blood disorders called porphyrias.

This medicine should not be used if you are allergic to any of its ingredients. Please inform your doctor or pharmacist if you havepreviously experienced such anallergy.

If you feel you haveexperienced an allergic reaction, stop using this medicine and inform yourdoctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy orbreastfeeding. However, other medicines may be safely used in pregnancy orbreastfeeding providing the benefits to the mother outweigh the risks to theunborn baby. Always inform your doctor if you are pregnant or planning apregnancy, before using any medicine.

• Valproate is known to have potentially harmful effects on a developing baby.
• It is vital that women with epilepsy receive specialist advice before getting pregnant, so they are well informed of potential risks and benefits of continuing antiepileptic treatment. Pregnant women taking antiepileptic medicine have a higher risk of carrying a baby with developmental problems and malformations. However, if a woman with epilepsy stops treatment because she is pregnant, there is a risk of seizures that can harm both mother and baby.
• Women who decide to try for a baby while taking valproate should start taking folic acid daily as soon as contraception is stopped, as this may reduce the risk of neural tube defects such as spina bifida in the baby.Ask your doctor for advice on the dose to take. Your doctor may recommend that you take 5mg daily.
• Women who continue to take valproate during a pregnancy should, wherever possible, be prescribed valproate on its own, in the lowest effective dose, in doses that are split over the day, and if possible as a prolonged-release brand. These measures can help minimise the risk to the baby. Specialist medical advice must be sought.
• Valproate should not be used for bipolar disorder in women who are pregnant, unless your doctor considers it essential because other treatments are ineffective or not tolerated.
• Valproate passes into breast milk in small amounts, but there have been no reports of harmful effects from this on nursing infants. Breastfeeding is considered acceptable for women taking this medicine. Seek further medical advice from your doctor.

Label warnings

• This medication is to be swallowed whole, not chewed.
• Do not stop taking this medication except on your doctor's advice.

Side effects

Medicines and their possible side effects can affect individualpeople in different ways. The following are some of the side effects that areknown to be associated with this medicine. Just because a side effect is statedhere does not mean that all people using this medicine will experience thator any side effect.

• Disturbances of the gut such as diarrhoea, nausea, vomiting or abdominal pain.
• Increased appetite and weight gain.
• Decrease in the number of platelets in the blood (thrombocytopenia).
• Temporary hair loss -– regrowth may be curly.
• Increased alertness.
• Aggression.
• Hyperactivity.
• Shaky movements and unsteady walk (ataxia).
• Tremor.
• Inflammation of blood vessels (vasculitis).
• Drowsiness.
• Confusion.
• Liver disorders.
• Irregular or stopping of menstrual periods.
• Skin rashes.
• Decreased numbers of white blood cells in the blood (leucopenia).
• Anaemia.
• Acne.
• Increased hair growth (hirsutism).
• Inflammation of the pancreas (pancreatitis).

The side effects listed above may not include all of the sideeffects reported by the medicine'smanufacturer.

For moreinformation about any other possible risks associated with this medicine,please read the information provided with the medicine or consult your doctoror pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicinesyou are already taking, including those bought without a prescription andherbal medicines, before you start treatment with this medicine. Similarly,check with your doctor or pharmacist before taking any new medicines whiletaking this one, to ensure that thecombination is safe.

Sodium valproate may increase the blood levels of the followingmedicines. As this could increase the risk of their side effects, your doctormay need to reduce the dose of these medicines if you taken them in combinationwith sodium valproate:

• benzodiazepines such as lorazepam
• bupropion
• lamotrigine (sodium valproate may also increase the risk of skin reactions associated with lamotrigine)
• phenobarbital
• phenytoin (phenytoin blood levels should be monitored if taken with sodium valproate)
• primidone
• tricyclic antidepressants such as amitriptyline and nortriptyline
• zidovudine.

There may be increased drowsiness and sedation if sodiumvalproate is taken with benzodiazepines, eg diazepam.

There may be an increased risk of side effects on the liver ifsodium valproate is taken with phenytoin or carbamazepine.

There may be an increased chance of side effects such asdizziness, tiredness, blurred vision and vomiting if sodium valproate is takenwith carbamazepine.

The following medicines may increase the blood level of sodiumvalproate:

• cimetidine
• felbamate
• large repeated doses of aspirin.

The following medicines may decrease the blood level of sodiumvalproate:

• carbapenem antibiotics, eg imipenem
• carbamazepine
• phenytoin
• phenobarbital
• primidone.

Colestyramine may reduce the absorption of sodium valproate fromthe gut. This can be minimised by separating doses of these medicines by atleast three hours.

It is recommended that people who are taking any antiepileptic medicines should avoid taking the herbal remedy St John's wort (Hypericum perforatum). This is because St John's wort may affect the level of antiepileptic medicines in the blood and could increase the risk of seizures.

There may be an increased risk of a drop in white blood cellcount if olanzapine is taken with sodium valproate. If you are taking olanzapine incombination with sodium valproate it is important to tell your doctor if youexperience any of the following symptoms: sore throat, mouth ulcers, hightemperature (fever), or general illness or infection. Your doctor may want totake a blood test to check your blood cells.

Other medicines containing the same active ingredient

Sodium valproate crushable tablets, enteric-coated tablets andoral solution are also available without a brand name, ie as thegeneric medicine.