EPILIM^® CHRONO

(Sodium valproate/ Valproic acid)

QUALITATIVE AND QUANTITATIVE COMPOSITION

Active constituents

Each tablet contains 333mg Sodium Valproate and 145mg Valproic Acid equivalent to 500mg sodium valproate.

PHARMACEUTICAL FORM

Prolonged release tablet

CLINICAL PARTICULARS

Therapeutic indications

In the treatment of generalized or partial epilepsy, particularly with the following patterns of seizures :

  - absence

  - myoclonic

  - tonic-don

  - atonic

  - mixed

As well as, for partial epilepsy :

  - simple or complex seizures

  - secondary generalized seizures

  - specific syndromes (West, Lennox-Gastaut)

Treatment and prevention of mania associated with bipolar disorder

Dosage and method of administration

Epilim Chrono tablets are for oral administration.

Epilim Chrono is a prolonged release formulation of Epilim which reduces peak concentration and ensures more even plasma concentrations throughout the day.

Epilim Chrono 500 may be given once or twice daily. The tablets should be swallowed whole and not crushed or chewed.

Daily dosage requirements vary according to age and body weight.

In patients where adequate control has been achieved Epilim Chrono formulations are interchangeable with other conventional or prolonged release formulations on an equivalent daily dosage basis.

Monotherapy

Usual requirements are as follows:

Adults

Dosage should start at 500mg daily increasing by 200mg at three-day intervals until control is achieved. This is generally within the dosage range 1000mg to 2000mg per day, ie 20-30mg/kg body weight. Where adequate control is not achieved within this range the dose may be further increased to 2500mg per day.

Children over 20kg

Initial dosage should be 500mg/day (irrespective of weight) with spaced increases until control is achieved; this is usually within the range 20-30mg/kg body weight per day. Where adequate control is not achieved within this range the dose may be increased to 35mg/kg body weight per day.

Children under 20kg

An alternative formulation of Epilim should be used in this group of patients, due to the tablet size and need for dose titration. Epilim Liquid (sugar free) or Epilim Syrup are alternatives.

Elderly

Although the pharmacokinetics of valproate are modified in the elderly, they have limited clinical significance and dosage should be determined by seizure control. The volume of distribution is increased in the elderly and because of decreased binding to serum albumin. the proportion of free drug is increased. This will affect the clinical interpretation of plasma valproic acid levels.

In patients with renal insufficiency

It may be necessary to decrease dosage. Dosage should he adjusted according to clinical monitoring since monitoring of plasma concentrations may be misleading (see Pharmacokinetic properties)

In patients with hepatic insufficiency

Salicylates should not be used concomitantly with valproate since they employ the same metabolic pathway (see Special warnings and precaution for use and undesirable effects).

Liver dysfunction, including hepatic failure resulting in fatalities, has occurred in patients whose treatment included valproic acid (see Contraindications and Special warning and special precaution for use).

Salicylates should not be used in children under 16 years (see Aspirin/salicylate product information on Reye's syndrome). In addition in conjunction with Epilim concomitant use in children under 3 years can increase the risk of liver toxicity (see Special warnings).

Combined therapy

When starting Epilim in patients already on other anticonvulsants, these should be tapered slowly; initiation of Epilim therapy should then be gradual, with target dose being reached after about 2 weeks. In certain cases it may be necessary to raise the dose by 5 to 10mg/kg/day when used in combination with anticonvulsants which induce liver enzyme activity, e.g. phenytoin, phenobarbitone and carbamazepine Once known enzyme inducers have been withdrawn it may be possible to maintain seizure control on a reduced dose of Epilim. When barbiturates are being administered concomitantly and particularly if sedation is observed (particularly in children) the dosage of barbiturate should be reduced.

NB: In children requiring doses higher than 40mg/kg/day clinical chemistry and haematological parameters should be monitored.

Optimum dosage is mainly determined by seizure control and routine measurement of plasma levels is unnecessary. However, a method for measurement of plasma levels is available and may be helpful where there is poor control or side effects are suspected (see Pharmacokinetic properties).

In treatment and prevention of mania associated with bipolar disorders:

Adults

The recommended initial dose is 1000mg/day. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose, which produces the desired clinical effects. The recommended initial dose is 1000mg and 2000mg daily. In exceptional cases, the dose may be increased to not more than 3000mg daily. Doses should be adjusted according to individual clinical response. Prophylactic treatment should be established individually with the lowerst effective dose.

Contraindications

  - Active liver disease

  - Personal or family history of severe hepatic dysfunction, especially drug related

  - Hypersensitivity to sodium valproate

  - Porphyria

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