Posology : מינונים

4.2.     Posology and method of administration

Orfiril injection solution is used if oral sodium valproate therapy cannot be given.
Note:
In infants, sodium valproate is the first-line drug only in exceptional cases; it should be used only with great caution and after careful consideration of the risk-benefit ration and, if possible, as monotherapy.

Orfiril injection is intended exclusively for intravenous administration.
The dosage should be determined according to age and weight and monitored individually by the physician on the basis of concentration determinations. Close monitoring of plasma levels and - if necessary - dosage adjustments have to be performed during the change-over to a parenteral therapy, during the parenteral therapy and during the switch back to oral therapy, in particular in such patients receiving higher doses of valproate or in patients receiving medicinal products potentially influencing the metabolism of valproate. Therapeutic efficacy is usually reached at plasma levels between 50 and 100 mg/L (340-700 mol/L). The mean daily dosages during maintenance treatment are as follows:

Children                            30 mg sodium valproate/kg body weight Adolescents                         25 mg sodium valproate/kg body weight Adults                              20 mg sodium valproate/kg body weight 

Higher maintenance doses for children and adolescents arise from higher valproate clearence values in these patients.
Starting of treatment and continuation of maintenance treatment in patients on valproate: 
Children and adults
To a new patient, initially a 5-10 mg/kg bolus dose as a slow intravenous (i.v.) injection over 3-5 minutes of sodium valproate is recommended. The dosage should be elevated by 5 mg/kg every 4 - 7 days to the recommended maintenance dose for each age group, or until a satisfactory clinical response is achieved. The total daily dose should be divided in three to four single administrations. To a patient previously on the medicinal product, an equivalent of the usual oral single dose (mg) as a slow intravenous (i.v.) injection over 3-5 minutes or as a short infusion is recommended; if necessary, the administration is continued as repeated injections every 6 hours, or as a slow intravenous infusion at 0.6-1 mg/kg/h until the patient can take the medicine orally.
For children, a maintenance dose of 30 mg/kg/day of sodium valproate is recommended, but if adequate seizure control is not achieved, the dose can be elevated to 40 mg/kg/day. In such cases, plasma valproic acid levels should be monitored frequently. It should be noted that in infants younger than 2 months, the elimination half-life of valproic acid might be up to 60 h. This should be taken in consideration when increasing the dosage to maintenance treatment. The maximal dose recommended for adults is 2400 mg/day.

In patients with renal failure, the rise in free valproic acid in the plasma must be taken into consideration and the dose reduced accordingly.

Method of administration
Orfiril injection may be given by slow intravenous injection or by infusion in 0.9 % saline or 5% dextrose.

Duration of treatment
The intravenous administration of Orfiril injection should be replaced by oral therapy as soon as practicable. In the clinical studies, there is no experience of more than a few days treatment with Orfiril injection.