SODIUM VALPROATE WOCKHARDT SOLUTION FOR INJECTION OR INFUSION 100MG/ML [SIN15343P]

Product Info

SODIUM VALPROATE WOCKHARDT SOLUTION FOR INJECTION OR INFUSION 100MG/ML

[SIN15343P]

4.1 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.

4.2 Posology and method of administration

Sodium valproate injection may be given by direct slow intravenous injection or by infusion using a separate intravenous line in normal saline, dextrose 5%, or dextrose saline.

Dosage
Dosage requirements vary according to age and body weight.

Each vial of sodium valproate injection is for single dose injection only. For instructions on preparation and dilution of sodium valproate injection before administration (see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

Sodium valproate injection 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 oral sodium valproate 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.

Sodium valproate injection should be replaced by oral sodium valproate 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 haematological parameters should be monitored.

Use in the elderly
Although the pharmacokinetics of sodium 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 the dosage. Dosage should be adjusted according to clinical monitoring since monitoring of plasma concentrations may be misleading (see section 5.2 – 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 sodium valproate since they employ the same metabolic pathway (see also sections 4.4 and 4.8 – 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 sections 4.3 and 4.4 – 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 sodium valproate, concomitant use in children under 3 years can increase the risk of liver toxicity (see section 4.4.1 – 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
Valproate 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 (see sections 4.3, 4.4 and 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Valproate is prescribed and dispensed according to the Valproate Pregnancy Prevention in Female Children and Women of Childbearing Potential (see sections 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The benefit and risk should be carefully reconsidered at regular treatment reviews (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
In the exceptional circumstance when valproate is the only treatment option during pregnancy in epileptic women, valproate 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. (see section 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Combined Therapy
When starting sodium valproate injection in patients already on other anticonvulsants, these should be tapered slowly. Initiation of sodium valproate injection therapy should then be gradual, with target dose being reached after about two 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, phenobarbital and carbamazepine. Once known enzyme inducers have been withdrawn it may be possible to maintain seizure control on a reduced dose of sodium valproate injection.

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 section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.3 Contraindications

Sodium Valproate 100mg/ml Solution for Injection or Infusion is contraindicated in the following situations:

• In pregnancy unless there is no suitable alternative treatment (see section 4.4 and 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• In women of childbearing potential, unless the conditions of the pregnancy prevention are fulfilled (see section 4.4 and 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• Active liver disease

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

• Patients with known urea cycle disorders (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information

• Porphyria

• Valproate is contraindicated in patients known to have mitochondrial disorders caused by mutations in the nuclear gene encoding the 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 section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)