Posology : מינונים

4.2. Posology and method of administration
Posology
Treatment with Timonil retard should be started with a low, individualised, initial dose depending on the nature and severity of the disease. This is then gradually increased until the most effective maintenance dose is found.
The daily dose is generally given in 1 – 2 single doses.
The general daily dosage range lies between 400 -1200 mg carbamazepine.
A total daily dose of 1600 mg should generally not be exceeded, since increased side effects occur at higher doses.


The therapeutic dose should be established, especially in combination therapy, by measuring the plasma levels and depending on the efficacy. Experience has shown that the therapeutic carbamazepine concentration is between 4 and 12 µg/mL.

In some instances the required dosage can vary considerably from the specified initial and maintenance doses (e.g. due to acceleration of metabolism by enzyme induction or due to drug interactions in combined medication).

Timonil retard should preferably be used to treat epilepsy as the sole drug (monotherapy).
The treatment should be supervised by a specialist with experience in the treatment of epilepsy. If the patient is switched to Timonil retard, the dose of the previously used antiepileptic must be slowly reduced.

The following general dosage scheme is recommended for the treatment of epileptic seizures:

Timonil retard                       Timonil retard
Initial daily dose               Daily maintenance dose
Adults              200 – 300 mg in the evening      200 – 600 mg in the morning 400 – 600 mg in the evening
Children
6 - 10 years        150 – 200 mg in the evening      200 mg in the morning 200 – 400 mg in the evening
11 - 15 years       150 – 200 mg in the evening      200 – 400 mg in the morning 400 – 600 mg in the evening

Paediatric population

For children under the age of 6 years non-prolonged release pharmaceutical forms are available for initial and maintenance doses (suspension or tablets).
For children under the age of 4 years, clinical experience has shown that, after initial doses (20 - 60 mg) of rapid release pharmaceutical forms , it is preferable to use Timonil retard in the daily dosage to date divided into two doses (as ½ or ¼ prolonged-release tablet if necessary). This can be increased by 20 - 60 mg carbamazepine every second day to the therapeutically required dose. However, the dose ranges given below should not be exceeded.

For children over the age of 4 years, clinical experience has shown that the initial dose may be 100 mg carbamazepine per day. This daily dose can be increased by up to 100 mg carbamazepine every second day or weekly to the required dose. However, the dose ranges given below should not be exceeded.

The following dosage recommendations apply to prolonged-release tablets: 
Epilepsy:
In general the adult initial dose of 200 – 400 mg carbamazepine/day can slowly be increased to the maintenance dose of 600 – 1200 mg/day.
In general the maintenance dose in children is 10 – 20 mg/kg body weight per day.

Recommended dosage scheme: see above.

Trigeminal neuralgia:
The daily dose is increased from an initial dose of 150 - 400 mg carbamazepine until freedom from pain is achieved - with an average dose of 300 - 900 mg carbamazepine (in 1 - 

2 divided doses). In some cases it is then possible to continue treatment with a lower maintenance dose of 300 - 450 mg carbamazepine/day.
An initial dose of 150 - 200 mg carbamazepine/day in the morning or evening is adequate in elderly and sensitive patients.

Mania and Prophylaxis of manic-depressive phases:
The initial dose, which is usually sufficient as a maintenance dose as well, is 200 – 400 mg carbamazepine daily. If necessary, the dose may be increased to 600 – 900 mg carbamazepine daily (in 2 divided doses).

Warnings:
A lower dosage is indicated in patients with serious cardiovascular diseases, in liver or kidney dysfunction and in the elderly.

Before deciding to initiate treatment, patients of Han-Chinese or Thai origin should whenever possible be screened for HLA-B*1502 as this allele strongly predicts the risk of severe carbamazepine-associated SJS (see information on genetic testings and cutaneous reactions in section 4.4).

Method of administration
The prolonged-release tablets are divisible and may either be swallowed whole during or after meals with sufficient liquid (e.g. a glass of water) or first be allowed to dissolve (become suspended) in water. If the tablets are suspended this should be done immediately before being administered.

In some cases, division of the daily dose into 4 - 5 doses has proved particularly effective. In these cases, non-prolonged release pharmaceutical forms of carbamazepine are to be preferred to prolonged release pharmaceutical forms.

The duration of treatment depends on the indication and the individual response of the patient. The medication must never be discontinued by the patient him/herself without permission.

The duration of treatment varies from individual to individual and is set by the attending physician.

Antiepileptic treatment is fundamentally a long-term therapy. The decision concerning dosage adjustment, duration and cessation of treatment with Timonil retard must be made in each case by a specialist with experience in the treatment of epilepsy.

On the basis of fundamental considerations, the medicinal product should not be changed for patients free of seizures, except for medical reasons, as even slight plasma level fluctuations might cause relapses or intoxication due to the narrow therapeutic range of the active ingredient.

In general, a reduction in dose or cessation of treatment should not be considered before the patient has been free of seizures for at least two or three years.

Treatment must be discontinued with a stepwise reduction in dose over one to two years.
Children can be allowed to outgrow their dose per kg body weight instead of carrying out an age-appropriate adjustment of the dosage, provided the EEG findings do not deteriorate.

When treating neuralgia, it has proved effective to give a maintenance dose just sufficient to abolish pain for a few weeks. The dose should then be cautiously reduced to determine whether spontaneous remission has occurred in the meantime.

If pain recurs, then the original maintenance dose should be continued.

Prophylaxis of manic-depressive phases is long term treatment.