EPILIM® 400 MG POWDER FOR INJECTION / INFUSION [SIN05215P]

Product Info

EPILIM® 400 MG POWDER FOR INJECTION / INFUSION

[SIN05215P]

Therapeutic Indications
The treatment of epileptic patients who would normally be maintained on oral sodium valproate, and for whom oral therapy is temporarily not possible.
In the treatment of generalized or partial epilepsy, particularly 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)

Posology and Method of Administration
Epilim Intravenous may be given by direct slow intravenous injection or by infusion using a separate intravenous line in normal saline, dextrose 5%, or dextrose saline.

Epilepsy
Daily dosage requirements vary according to age and body weight.

To reconstitute, inject the solvent provided (4ml) into the vial, allow to dissolve and extract the appropriate dose. Due to displacement of solvent by sodium valproate the concentration of reconstituted sodium valproate is 100mg/ml.

Each vial of Epilim Intravenous is for single dose injection only. It should be reconstituted immediately prior to use and infusion solutions containing it used within 24 hours. Any unused portion should be discarded (see Instructions for Use/Handling – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Epilim Intravenous should not be administered via the same IV line as other IV additives. The intravenous solution is suitable for infusion by PVC, polyethylene or glass containers.

Patients already satisfactorily treated with Epilim may be continued at their current dosage using continuous or repeated infusion. Other patients may be given a slow intravenous injection over 3–5 minutes, usually 400–800mg depending on body weight (up to 10mg/kg) followed by continuous or repeated infusion up to a maximum of 2500mg/day.

Epilim Intravenous should be replaced by oral Epilim therapy as soon as practicable.

Use with children
Daily requirement for children is usually in the range 20–30mg/kg/day and method of administration is as above. Where adequate control is not achieved within this range the dose may be increased up to 40mg/kg/day 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.

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 Contraindications 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. 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).

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)