Regulatory Information
HSA regulatory responsibility and product classification details
Regulatory Responsibility
Product Classification
Formulation Information
INJECTION, SOLUTION
**4.2. Posology and method of administration** SODIUM VALPROATE AGUETTANT may be given by direct slow intravenous injection or by infusion using a separate intravenous line in normal saline or dextrose 5%. _Epilepsy_ Daily dosage requirements vary according to age and body weight. SODIUM VALPROATE AGUETTANT 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 SODIUM VALPROATE AGUETTANT 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 AGUETTANT should be replaced by oral 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 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 in patients with renal insufficiency to decrease the dosage, or to increase the dosage in patients on haemodialysis. Sodium 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_). 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 SODIUM VALPROATE AGUETTANT, 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, female adolescents, women of childbearing potential and pregnant women SODIUM VALPROATE AGUETTANT 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, 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_ When starting SODIUM VALPROATE AGUETTANT in patients already on other anticonvulsants, these should be tapered slowly: initiation of SODIUM VALPROATE AGUETTANT 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 SODIUM VALPROATE AGUETTANT. 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 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_).
INTRAVENOUS
Medical Information
**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. 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)
**4.3. Contraindications** - 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 there is no suitable alternative treatment and unless the physician has provided information in regards to the potential effects of valproate during pregnancy and recommendations on the use of valproate (see section 4.4 and 4.6 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_) - History of hypersensitivity to sodium valproate, divalproate, valpromide 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_. - Acute liver disease. - Chronic hepatitis. - Personal or family history of severe hepatic dysfunction, particularly drug induced. - Porphyria. - 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_). - Valproate is contraindicated in patients known to have mitochondrial disorders caused by mutations in the nuclear gene encoding the mitochondrial enzyme polymerase gamma (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_). - Known systemic primary carnitine deficiency with uncorrected hypocarnitinaemia (see section 4.4 “Patients at risk of hypocarnitinaemia” – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_).
N03AG01
valproic acid
Manufacturer Information
AGUETTANT ASIA PACIFIC PTE. LTD.
Laboratoire Aguettant