Posology : מינונים

4.2   Posology and method of administration

Treatment with Inovelon tablets should be initiated by a physician specialised in paediatrics or neurology with experience in the treatment of epilepsy.

Posology

Use in children from one year to less than four years of age
Patients not receiving valproic acid (as sodium):
Treatment should be initiated at a dose of 10 mg/kg/day administered in two equally divided doses separated by approximately 12 hours. According to clinical response and tolerability, the dose may be increased by up to 10 mg/kg/day every third day to a target dose of 45 mg/kg/day administered in two equally divided doses separated by approximately 12 hours. For this patient population, the maximum recommended dose is 45 mg/kg/day.

Patients receiving valproic acid (as sodium):
As valproic acid (as sodium) significantly decreases clearance of rufinamide, a lower maximum dose of Inovelon tablets is recommended for patients being co- administered valproic acid (as sodium). Treatment should be initiated at a dose of 10 mg/kg/day administered in two equally divided doses separated by approximately 12 hours. According to clinical response and tolerability, the dose may be increased by up to 10 mg/kg/day every third day to a target dose of 30 mg/kg/day administered in two equally divided doses separated by approximately 12 hours.
For this patient population, the maximum recommended dose is 30 mg/kg/day.

If the recommended calculated dose of Inovelon tablets is not achievable, the dose should be given to the nearest whole 100 mg tablet.

Use in children four years of age or older and less than 30 kg 
Patients <30 kg not receiving valproic acid (as sodium):
Treatment should be initiated at a daily dose of 200 mg. According to clinical response and tolerability, the dose may be increased by 200 mg/day increments, as frequently as every third day, up to a maximum recommended dose of 1000 mg/day.

Doses of up to 3600 mg/day have been studied in a limited number of patients.

Patients <30 kg also receiving valproic acid (as sodium):
As valproic acid (as sodium) significantly decreases clearance of Inovelon tablets, a lower maximum dose of Inovelon tablets is recommended for patients <30 kg being co-administered valproic acid (as sodium). Treatment should be initiated at a daily dose of 200 mg. According to clinical response and tolerability, after a minimum of 2 days the dose may be increased by 200 mg/day, to the maximum recommended dose of 600 mg/day.

Use in adults, adolescents and children four years of age or older of 30 kg or over 
Patients >30 kg not receiving valproic acid (as sodium):
Treatment should be initiated at a daily dose of 400 mg. According to clinical response and tolerability, the dose may be increased by 400 mg/day increments, as frequently as every other day, up to a maximum recommended dose as indicated in the table below.

Weight range          30.0 – 50.0 kg         50.1 – 70.0 kg         ≥70.1 kg Maximum               1,800 mg/day           2,400 mg/day           3,200 mg/day recommended dose

Doses of up to 4,000 mg/day (in the 30 -50 kg range) or 4,800 mg/day (in the over 50 kg) have been studied in a limited number of patients.

Patients >30 kg also receiving valproic acid (as sodium):
Treatment should be initiated at a daily dose of 400 mg. According to clinical response and tolerability, the dose may be increased by 400 mg/day increments, as frequently as every other day, up to a maximum recommended dose as indicated in the table below.

Weight range           30.0 – 50.0 kg         50.1 – 70.0 kg         ≥70.1 kg Maximum                1,200 mg/day           1,600 mg/day           2,200 mg/day recommended dose

Elderly
There is limited information on the use of Inovelon tablets in older people. Since, the pharmacokinetics of rufinamide are not altered in older people (see Section 5.2), dosage adjustment is not required in patients over 65 years of age.


Renal impairment
A study in patients with severe renal impairment indicated that no dose adjustments are required for these patients (see Section 5.2).

Hepatic impairment
Use in patients with hepatic impairment has not been studied. Caution and careful dose titration is recommended when treating patients with mild to moderate hepatic impairment. Therefore, use in patients with severe hepatic impairment is not recommended.

Discontinuation of Inovelon tablets
When Inovelon tablets treatment is to be discontinued, it should be withdrawn gradually. In clinical trials Inovelon tablets discontinuation was achieved by reducing the dose by approximately 25% every two days (see section 4.4).

In the case of one or more missed doses, individualised clinical judgement is necessary.

Uncontrolled open-label studies suggest sustained long-term efficacy, although no controlled study has been conducted for longer than three months.

Paediatric population
The safety and efficacy of rufinamide in new-born infants or infants and toddlers aged less than 1 year have not been established. No data are available. (see section 5.2) 

Method of administration
Rufinamide is for oral use. The tablet should be taken twice daily with water in the morning and in the evening, in two equally divided doses., Inovelon tablets should be administered with food (see section 5.2). If the patient has difficulty with swallowing, tablets can be crushed and administered in half a glass of water. Alternatively, use the score line to break the tablet into two equal halves.