EPILIM 200 TABLET 200 MG [SIN05690P]

Product Info

EPILIM 200 TABLET 200 MG

[SIN05690P]

Therapeutic Indications
Epilepsy
For oral administration in the treatment of generalized, partial or other epilepsy with the following patterns of seizures:

• absence

• myoclonic

• tonic-clonic

• atonic

• mixed

As well as, for partial epilepsy:

• simple or complex seizures

• secondary generalized seizures

• specific syndromes (West, Lennox-Gastaut)

Mania
For treatment of mania where other therapy has proved inadequate or is inappropriate.

Posology and Method of Administration
Epilim Chrono Controlled Release 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 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.
In view of the sustained release process and the nature of the excipients in the formula, the inert matrix of the granules is not absorbed by the digestive tract. It is eliminated in the stools after the active substances have been released.

Epilim Enteric Coated Tablets are for oral administration.
Daily dosage requirements vary according to age and body weight.
Epilim tablets may be given twice daily. Tablets should be swallowed whole and not crushed or chewed.
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.

Epilim Syrup is for oral administration.
Daily dosage requirements vary according to age and body weight.
Epilim Syrup may be given twice daily. If it is necessary to dilute Epilim Syrup, the recommended diluent is Syrup BP, but syrup containing SO₂ as a preservative should not be used. The diluted product will have a 14-day shelf life.

Dosage
Epilepsy
Usual requirements are as follows:

Adults
Dosage should start at 600mg 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 400mg/day (irrespective of weight) with spaced increases until control is achieved; this is usually within the range 20–30mg/kg body weight per day.

Children under 20kg
20mg/kg of body weight per day; in severe cases this may be increased but only in patients in whom plasma valproic acid levels can be monitored. Above 40mg/kg/day, clinical chemistry and Hematological parameters should be monitored. Epilim syrup should be used in this group of patients.

Use in the 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 be adjusted according to clinical monitoring since monitoring of plasma concentrations may be misleading (see Pharmacokinetic Properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

In patients with hepatic insufficiency
Salicylates should not be used concomitantly with valproate since they employ the same metabolic pathway (see also Special Warnings and Precautions for Use and Undesirable Effects – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Liver dysfunction, including hepatic failure resulting in fatalities, has occurred in patients whose treatment included valproic acid (see Contra-indications and Special Warnings and Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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 should be avoided as it can increase the risk of liver toxicity (see Special Warnings – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

In female children, women of childbearing potential and pregnant women
Epilim must be initiated and supervised by a specialist experienced in the management of epilepsy or bipolar disorder. Valproate should not be used in female children and women of childbearing potential unless other treatments are ineffective or not tolerated.

In the exceptional circumstance when valproate is the only treatment option during pregnancy in epileptic women, Epilim should preferably be prescribed as monotherapy and at the lowest effective dose, if possible as a prolonged release formulation. The daily dose of non-prolonged release formulations should be divided into at least two single doses during pregnancy.

Valproate is prescribed and dispensed according to the Valproate Pregnancy Prevention Program (See Pregnancy Prevention Program in Special Warnings and Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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, eg phenytoin, phenobarbital 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 Hematological 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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Mania
Initially dosage should start with 600mg daily increasing by 200mg/day at three-day intervals until control is achieved. This is generally within the range 1,000 to 2,000 mg/day (ie 20 to 30mg/kg/day). Where adequate control is not achieved within this range the dose may be further increased to 2,500mg/day.

Only for Bipolar indication
In children and adolescents:
The efficacy of Epilim for the treatment of manic episodes in bipolar disorder has not been established in patients aged less than 18 years. See Sections Special Warnings and Precautions for Use and Undesirable effects for safety information – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Contra-indications
Epilim is contraindicated in the following situations:

• Active liver disease

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

• Hypersensitivity to sodium valproate

• Porphyria

• Known urea cycle disorders

• Patients with known systemic primary carnitine deficiency with uncorrected hypocarnitinemia (see section Special warnings and special precautions for use Patients at risk of hypocarnitinemia – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

• Patients known to have mitochondrial disorders caused by mutations in the nuclear gene encoding mitochondrial enzyme polymerase γ (POLG, e.g. Alpers-Huttenlocher Syndrome) and in children under two years of age who are suspected of having a POLG-related disorder (see Special warnings – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• Treatment of epilepsy

  • in pregnancy unless there is no suitable alternative treatment (see Special Warnings and Precautions for Use and Pregnancy – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

  • in women of childbearing potential, unless there is no other alternative treatment and unless the conditions of the pregnancy prevention program are fulfilled (see Special Warnings and Precautions for Use and Pregnancy – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• Treatment of bipolar disorder

  • in pregnancy (see Special Warnings and Precautions for Use and Pregnancy – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

  • in women of childbearing potential, unless there is no other alternative treatment and unless the conditions of the pregnancy prevention program are fulfilled (see Special Warnings and Precautions for Use and Pregnancy – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).