Posology : מינונים

4.2    Posology and method of administration

Posology
It is recommended that therapy be initiated at a low dose followed by titration to an effective dose. Dose and titration rate should be guided by clinical response.

It is not necessary to monitor topiramate plasma concentrations to optimise therapy with TOPAMAX®.
On rare occasions, the addition of TOPAMAX® to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. Addition or withdrawal of phenytoin and carbamazepine to adjunctive therapy with TOPAMAX® may require adjustment of the dose of TOPAMAX®.

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In patients with or without a history of seizures or epilepsy, antiepileptic drugs (AEDs) including topiramate should be gradually withdrawn to minimise the potential for seizures or increased seizure frequency. In clinical trials, daily dosages were decreased in weekly intervals by 50-100 mg in adults with epilepsy and by 25-50 mg in adults receiving topiramate at doses up to 100 mg/day for migraine prophylaxis. In paediatric clinical trials, topiramate was gradually withdrawn over a 2-8 week period.
Adjunctive Therapy Epilepsy
Adults
Therapy should begin at 25 - 50 mg nightly for one week. Use of lower initial doses has been reported, but has not been studied systematically. Subsequently, at weekly or bi-weekly intervals, the dose should be increased by 25 - 50 to 100 mg/day and taken in two divided doses. Dose titration should be guided by clinical outcome. Some patients may achieve efficacy with once-a-day dosing.

In clinical trials as adjunctive therapy, 200 mg was effective and was the lowest dosage studied. This is therefore considered the minimum effective dose.

The usual daily dose is 200 - 400 mg in two divided doses. Individual patients have received doses as high as 1600 mg/day.
These dosing recommendations apply to all adults, including the elderly, in the absence of underlying renal disease. (See SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE) 

Children Aged 2 And Above
The recommended total daily dose of TOPAMAX® (topiramate) as adjunctive therapy is approximately 5 to 9 mg/kg/day in two divided doses. Titration should begin at 25 mg (or less, based on a range of 1 to 3 mg/kg/day) nightly for the first week. The dosage should then be increased at 1- or 2-week intervals by increments of 1 to 3 mg/kg/day (administered in two divided doses), to achieve optimal clinical response. Dose titration should be guided by clinical outcome.
Daily doses up to 30 mg/kg/day have been studied and were generally well tolerated.
Monotherapy epilepsy
General
When concomitant AEDs are withdrawn to achieve monotherapy with topiramate, consideration should be given to the effects this may have on seizure control. Unless safety concerns require an abrupt withdrawal of the concomitant AED, a gradual discontinuation at the rate of approximately one-third of the concomitant AED dose every 2 weeks is recommended.

When enzyme inducing drugs are withdrawn, topiramate levels will increase. A decrease in TOPAMAX® dosage may be required if clinically indicated.

Adults
Dose and titration should be guided by clinical response. Titration should begin at 25 mg nightly for 1 week. The dosage should then be increased at 1- or 2-week intervals by increments of 25 or 50 mg/day, administered in two divided doses. If the patient is unable to tolerate the titration regimen, smaller increments or longer intervals between increments can be used.

The recommended initial target dose for topiramate monotherapy in adults is 100 mg/day.and the maximum recommended daily dose is 500. Some patients with refractory forms of epilepsy have tolerated topiramate monotherapy at doses of 1,000 mg/day. These dosing recommendations apply to all adults including the elderly in the absence of underlying renal disease.

Children
Dose and titration rate in children should be guided by clinical outcome. Treatment of children years and above should begin at 0.5 to 1 mg/kg nightly for the first week. The dosage should then be increased at 1 or 2 week intervals by increments of 0.5 to 1 mg/kg/day, administered in two divided doses. If the child is unable to tolerate the titration regimen, smaller increments or longer intervals between dose increments can be used.

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The recommended initial target dose range for topiramate monotherapy in children years and above is 100 to 400 mg/day. Children with recently diagnosed partial onset seizures have received doses of up to 500 mg/day

Migraine
Adults
The recommended total daily dose of topiramate for prophylaxis of migraine headache is 100 mg/day administered in two divided doses. Titration should begin at 25 mg nightly for 1 week. The dosage should then be increased in increments of 25 mg/day administered at 1-week intervals. If the patient is unable to tolerate the titration regimen, longer intervals between dose adjustments can be used.

Some patients may experience a benefit at a total daily dose of 50 mg/day. Patients have received a total daily dose up to 200 mg/day. This dose may be benefit in some patients, nevertheless, caution is advised due to an increase incidence of side effects.

Paediatric population
Topamax (topiramate) is not recommended for treatment or prevention of migraine in children due to insufficient data on safety and efficacy.

General dosing recommendations for Topamax in special patient populations Renal impairment
In patients with impaired renal function (CLCR ≤ 70 mL/min) topiramate should be administered with caution as the plasma and renal clearance of topiramate are decreased. Subjects with known renal impairment may require a longer time to reach steady-state at each dose. Half of the usual starting and maintenance dose is recommended (see section 5.2).

In patients with end-stage renal failure, since topiramate is removed from plasma by haemodialysis, a supplemental dose of Topamax equal to approximately one-half the daily dose should be administered on haemodialysis days. The supplemental dose should be administered in divided doses at the beginning and completion of the haemodialysis procedure. The supplemental dose may differ based on the characteristics of the dialysis equipment being used (see section 5.2).

Hepatic impairment
In patients with moderate to severe hepatic impairment topiramate should be administered with caution as the clearance of topiramate is decreased.

Elderly
No dose adjustment is required in the elderly population providing renal function is intact.

Female children and women of childbearing potential
Treatment with topiramate should be initiated and supervised by a physician experienced in the management of epilepsy or migraine.

Alternative therapeutic options should be considered in female children and women of childbearing potential. The need for topiramate treatment in these populations should be reassessed at least annually (see sections 4.3, 4.4 and 4.6).

Method of administration
Topamax is available in film-coated tablets for oral administration. It is recommended that film-coated tablets not be broken.
Topamax can be taken without regard to meals.