Posology : מינונים

4.2    Posology and method of administration

Posology
Brivaracetam solution for injection/infusion is an alternative route of administration for patients when oral administration is temporarily not feasible. There is no experience with twice daily intravenous administration of brivaracetam for a period longer than 4 days.

Adults
Brivaracetam may be initiated with either intravenous or oral administration. When converting from oral to intravenous administration or vice versa, the total daily dose and frequency of administration should be maintained.

The recommended starting dose is either 50 mg/day or 100 mg/day based on physician's assessment of required seizure reduction versus potential side effects. The dose should be administered in two equally divided doses, once in the morning and once in the evening. Based on individual patient response and tolerability, the dose may be adjusted in the dose range of 50 mg/day to 200 mg/day.

Children (from 4 years of age) and adolescents weighing 50 kg or more The recommended starting dose is 50mg/day. Brivaracetam may also be initiated at 100 mg/day based on physician's assessment of need for seizure control. The dose should be administered in two equally divided doses, once in the morning and once in the evening.The recommended maintenance dose is 100 mg/day. Based on individual patient response, the dose may be adjusted in the effective dose range of 50 mg/day to 200 mg/day.


Children (from 4 years of age) and adolescents weighing less than 50 kg The recommended starting dose is 1 mg/kg/day. Brivaracetam may also be initiated at 2 mg/kg/day based on physician's assessment of need for seizure control. The dose should be administered in two equally divided doses, once in the morning and once in the evening. The recommended maintenance dose is 2 mg/kg/day. Based on individual patient response, the dose may be adjusted in the effective dose range of 1 mg/kg/day to 4 mg/kg/day.

The following table summarises the recommended posology for children from 4 years of age and adolescents.

Children (≥4 years) and              Children (≥4 years) and adolescents ≥50 kg                   adolescents <50 kg

Administered in 2 equally            Administered in 2 equally divided doses                         divided doses
Therapeutic dose range          50 - 200 mg/day                      1 - 4 mg/kg/day Recommended starting dose       50 mg/day                            1 mg/kg/day (or 100 mg/day)*                     (or 2 mg/kg/day)*
Recommended maintenance         100 mg/day                           2 mg/kg/day dose
* Based on physician's assessment of need for seizure control.

Missed doses
If patients missed one dose or more, it is recommended that they take a single dose as soon as they remember and take the following dose at the usual morning or evening time. This may avoid the brivaracetam plasma concentration falling below the efficacy level and prevent breakthrough seizures from occurring.

Discontinuation
If brivaracetam has to be discontinued it is recommended to withdraw it gradually by 50 mg/day on a weekly basis. After 1 week of treatment at 50 mg/day, a final week of treatment at the dose of 20 mg/day is recommended.

Special populations

Elderly (65 years of age and above)
No dose adjustment is needed in elderly patients (see section 5.2).
The clinical experience in patients ≥ 65 years is limited.
Renal impairment
No dose adjustment is needed in patients with impaired renal function (see section 5.2). Brivaracetam is not recommended in end-stage renal disease patients undergoing dialysis due to lack of data.
Based on data in adults, no dose adjustment is necessary in paediatric patients with impaired renal function.

Hepatic impairment
Exposure to brivaracetam was increased in adult patients with chronic liver disease. In adults, a 50 mg/day starting dose should be considered. In children and adolescents weighing 50 kg or greater, a 50 mg/day starting dose is recommended. A maximum daily dose of 150 mg administered in 2 divided doses is recommended for all stages of hepatic impairment (see sections 4.4 and 5.2).
In children and adolescents weighing less than 50 kg, a 1 mg/kg/day starting dose is recommended.
The maximum dose should not exceed 3 mg/kg/day. No clinical data are available in paediatric patients with hepatic impairment.

Children less than 4 years
The safety and efficacy of brivaracetam in children aged less than 4 years have not yet been established.

Currently available data are described in section 4.8, 5.1, and 5.2 but no recommendation on a posology can be made.

Method of administration

- Intravenous bolus: brivaracetam may be administered as an intravenous bolus without dilution.
- Intravenous infusion: brivaracetam may be diluted in a compatible diluent and administered as a 15-minute intravenous infusion (see section 6.6). This medicinal product must not be mixed with other medicinal products.

Brivaracetam bolus injection or intravenous infusion has not been studied in acute conditions; e.g.
status epilepticus and is therefore not recommended for such conditions.