SODIUM VALPROATE ADVAGEN SOLUTION FOR INJECTION OR INFUSION 100MG/ML [SIN16992P]

Product Info

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

[SIN16992P]

4.1 Therapeutic indications

For the treatment of patients with epilepsy 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)

4.2 Posology and method of administration

Posology

Dosage

Daily dosage requirements vary according to age and body weight.

Each vial of Sodium valproate injection is for single dose injection only.

Adults

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 – 800 mg depending on body weight (up to 10 mg/kg) followed by continuous or repeated infusion up to a maximum of 2500 mg/day.

Sodium valproate injection should be replaced by oral sodium valproate therapy as soon as practicable.

Special populations

Paediatric population

Daily requirement for children is usually in the range 20 – 30 mg/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 40 mg/kg/day but only in patients in whom plasma valproic acid levels can be monitored. In children requiring doses higher than 40 mg/kg/day, clinical chemistry and haematological parameters should be monitored.

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.

Renal impairment

It may be necessary in patients with renal insufficiency to decrease the dosage, or to increase the dosage in patients on haemodialysis. Valproate is dialysable (see section 4.9 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Dosing should be modified according to clinical monitoring of the patient (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic impairment

Salicylates should not be used concomitantly with valproate since they employ the same metabolic pathway (see 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 of age (see aspirin/salicylate product information on Reye’s syndrome). In addition, in conjunction with valproate, concomitant use in children under 3 years of age 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).

Female children and women of childbearing potential

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).

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.

Combined therapy (see section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

When starting Sodium valproate injection in patients already on other anti- convulsants, these should be tapered slowly; initiation of Sodium valproate injection 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 – 10 mg/kg/day when used in combination with anti-convulsants 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.

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).

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.

Sodium valproate injection should not be administered via the same IV line as other IV additives. The intravenous solution is suitable for infusion by polyethylene or glass containers.

4.3 Contraindications

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

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

• Hypersensitivity to sodium valproate or any other excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

• Active liver disease, or 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).

• Porphyria.

• Patients with known systemic primary carnitine deficiency with uncorrected hypocarnitinemia

• 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).