Posology : מינונים

4.2     Posology and method of administration
Notes
When switching from previous (non-prolonged-release) dosage forms to Depalept chrono, care must be taken to ensure adequate serum levels of valproic acid.

In female children, female adolescents, women of childbearing potential and pregnant women Depalept chrono should be initiated and supervised by a specialist experienced in the management of epilepsy or bipolar disorder. Treatment should only be initiated if other treatments are ineffective or not tolerated (see Section 4.3, 4.4 and Section 4.6) and the benefit and risk should be carefully reconsidered at regular treatment reviews. Preferably Depalept chrono should 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.

Depalept Chrono is a prolonged-release formulation of Depalept which reduces peak plasma concentrations and ensures more regular plasma levels over a 24-hour period.
In view of the dosage strength this medicinal product is for use in adults and children weighing over than 17 kg only.
This dosage form is not appropriate for children under the age of 6 years (risk of choking).

Dosage
Epilepsy
The Initial daily dosage is usually 10-15 mg/kg, after which doses are increased up to the optimum dose (see Initiation of Depalept therapy)
The mean dosage is 20 -30 mg/kg per day. However, if seizures are not brought under control at this dosage it may be increased and patients must be closely monitored.

− In children, the usual dosage is about 30 mg/kg per day.
− In adults, the usual dosage is 20 to 30 mg/kg per day.
− In elderly patients, the dosage should be determined based on the control of seizures.
The daily dosage should be determined based on age and body weight, however, the significant variations in inter-individual sensitivity to valproate must be taken into account.
No clear correlation between the daily dose, serum levels and the therapeutic effect has been established: the dosage should be determined on the basis of the clinical response.
Determination of valproic acid plasma levels should be considered along with clinical monitoring when control of seizures is not achieved or when adverse effects are suspected. The effective therapeutic range is usually between 40 and 100 mg/L (300 to 700 μmol/L).

Initiation of Depalept therapy (oral administration):
• In patients in whom appropriate control has been obtained with immediate-release forms of Depalept, it is recommended that the daily dose be maintained when replacing treatment with Depalept Chrono.


•     If the patient is already being treated and is taking other antiepileptics, begin administering Depalept Chrono gradually, to reach the optimal dose in approximately two weeks, then reduce the concomitant treatments if necessary on the basis of treatment efficacy.
•     If the patient is not taking any other antiepileptics, the dosage should preferably be increased step- wise every 2 or 3 days, in order to reach the optimal dose in approximately one week.
•     If necessary, combination treatment with other antiepileptics should be instituted gradually (see 4.5 Interaction with other medicinal products and other forms of interaction).

Manic episodes in bipolar disorder
Adults
The daily dosage should be established and controlled individually by the treating physician. The initial recommended daily dose is 750 mg. In addition, in clinical trials a starting dose of 20 mg sodium valproate/kg body weight has also shown an acceptable safety profile. Prolonged-release formulations can be given once or twice daily. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect. The daily dose should be adapted to the clinical response to determine the lowest effective dose for the individual patient.
The average daily dose usually ranges between 1000 and 2000 mg sodium valproate. Patients receiving daily doses higher than 45 mg/kg body weight/day should be carefully monitored.
Continuation of treatment of manic episodes in bipolar disorder should be adapted individually using the lowest effective dose.

Children and adolescents
The efficacy of Ergenyl chrono for the treatment of manic episodes in bipolar disorder have not been established in patients aged less than 18 years.
For information on the safety profile in children, see section 4.8.

Method of administration
Oral use.
The daily dose should be administered in 1 dose or 2 divided doses, preferably during meals and should be swallowed whole with a glass of water, but not carbonated mineral water.
Administration of a single daily dose is possible in well controlled epilepsy.
In view of the sustained release process and the nature of the excipients in the formula, the inert matrix is not absorbed by the digestive tract; it is eliminated in the stools after the active substances have been released.

Initiation of Depalept therapy (oral administration):
• Liver function tests should be performed before starting treatment (see Section 4.3) and then periodically for the first 6 months, particularly in patients at risk (see Section 4.4).
• Blood tests (complete blood count including platelets, bleeding time and coagulation parameters) are recommended prior to treatment, then after 15 days and at the end of treatment, and also before any surgery, and in the event of hematomas or spontaneous bleeding (see Section 4.8).
• Patients with renal insufficiency: In patients with renal insufficiency, it may be necessary to decrease the dosage, or to increase the dosage in those receiving haemodialysis. Valproate is dialysable (see section 4.9). Dosage should be adjusted according to clinical monitoring of the patient (see section 4.4).