Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: G.L. Pharma GmbH, Schlossplatz 1, 8502 Lannach, Austria
Treatment of generalised, partial or other epilepsy.
Convulex capsules are for oral administration.
Daily dosage requirements vary according to age and body weight.
Convulex capsules may be given twice daily.
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 4.4 and 4.6) and the benefit and risk should be carefully reconsidered at regular treatment reviews.
Valproate is prescribed and dispensed according to the Valproate Pregnancy Prevention Programme (sections 4.3 and 4.4).
Valproate should preferably be prescribed as monotherapy and at the lowest effective dose, if possible as a prolonged release formulation. The daily dose should be divided into at least two single doses (see section 4.6).
Usual requirements are as follows:
Dosage should start at 600 mg daily, followed by gradual increases (approx. 300 mg) at three day intervals until control is achieved. This is generally within the dosage range 1000 mg to 2000 mg per day, i.e. 20-30 mg/kg body weight. Where adequate control is not achieved within this range, the dose may be further increased up to 2500 mg per day.
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.
Children over 20kg:
Initial dosage is usually not more than 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. Where adequate control is not achieved within this range the dose may be increased to 35mg/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 haematological parameters should be monitored.
Splitting the total daily dose into 2-4 intakes is generally recommended.
It may be necessary to decrease dosage. Dosage should be adjusted according to clinical monitoring since monitoring of plasma concentrations may be misleading (see section 5.2 Pharmacokinetic properties).
Salicylates should not be used concomitantly with valproate since they employ the same metabolic pathway (see also sections 4.4 Special warnings and precautions for use and 4.8 Undesirable effects).
Liver dysfunction, including hepatic failure resulting in fatalities, has occurred in patients whose treatment included valproic acid (see sections 4.3 Contraindications and 4.4 Special warnings and precautions for use).
Salicylates should not be used in children under 16 years (see aspirin/salicylate product information on Reye’s syndrome). In addition in conjunction with Convulex, concomitant use in children under 3 years can increase the risk of liver toxicity (see section 4.4.1 Special warnings).
Substitution:
A one to one dose relationship of Convulex and products containing sodium valproate has been demonstrated in pharmacokinetic trials. In patients previously receiving sodium valproate therapy, Convulex should be initiated at the same total daily dose.
Combined therapy:
When starting Convulex in patients already on other anticonvulsants, these should be tapered slowly; initiation of Convulex 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, e.g. phenytoin, phenobarbitone and carbamazepine. Once known enzyme inducers have been withdrawn it may be possible to maintain seizure control on a reduced dose of Convulex. 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 Pharmacokinetic properties).
Cases of accidental and deliberate valproate overdosage have been reported.
At plasma concentrations of up to 5-6 times the maximum therapeutic levels, there are unlikely to be any symptoms other than nausea, vomiting and dizziness.
Clinical signs of massive overdose, i.e. plasma concentration 10 to 20 times maximum therapeutic levels, usually include CNS depression or coma with muscular hypotonia, hyporeflexia, miosis, impaired respiratory function.
Symptoms may however be variable and seizures have been reported in the presence of very high plasma levels (see also section 5.2 Pharmacokinetic Properties). Cases of intracranial hypertension related to cerebral oedema have been reported.
Hospital management of overdose should be symptomatic, including cardio-respiratory monitoring. Gastric lavage may be useful up to 10 to 12 hours following ingestion.
Haemodialysis and haemoperfusion have been used successfully.
Naloxone has been successfully used in a few isolated cases, sometimes in association with activated charcoal given orally. Deaths have occurred following massive overdose; nevertheless, a favourable outcome is usual.
5 years.
Do not store above 25°C.
Do not refrigerate or freeze.
Keep in the original package in order to protect from light and moisture.
Blister packs:
Upper: PVC/PVDC or PVC-foil
Lower: aluminium foil
Outer box: carton folding box
Pack size: 100, 30
No special requirements.
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