Posology : מינונים

4.2 Posology and method of administration
Posology
Levetiracetam therapy can be initiated with either intravenous or oral administration.
Conversion to or from oral to intravenous administration can be done directly without titration. The total daily dose and frequency of administration should be maintained.

Monotherapy for adults and adolescents from 16 years of age
The recommended starting dose is 250 mg twice daily which should be increased to an initial therapeutic dose of 500 mg twice daily after two weeks. The dose can be further increased by 250 mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1500 mg twice daily.

Add-on therapy for adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more
The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment.
Depending upon the clinical response and tolerability, the daily dose can be increased up to 1,500 mg twice daily. Dose changes can be made in 500 mg twice daily increases or decreases every two to four weeks.

Duration of treatment
There is no experience with administration of intravenous levetiracetam for longer period than 4 days.

Discontinuation
If levetiracetam has to be discontinued it is recommended to withdraw it gradually (e.g. in adults and adolescents weighing more than 50 kg: 500 mg decreases twice daily every two to four weeks; in children and adolescents weighing less than 50 kg: dose decrease should not exceed 10 mg/kg twice daily every two weeks).

Special populations
Elderly (65 years and older)
Adjustment of the dose is recommended in elderly patients with compromised renal function (see “Renal impairment” below).

Renal impairment
The daily dose must be individualised according to renal function.
For adult patients, refer to the following table and adjust the dose as indicated. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in ml/min is needed. The CLcr in ml/min may be estimated from serum creatinine (mg/dl) determination, for adults and adolescents weighing 50 kg or more, the following formula:



Then CLcr is adjusted for body surface area (BSA) as follows:



Dosing adjustment for adult and adolescents patients weighing more than 50 kg with impaired renal function:
Group                                    Creatinine clearance         Dose and frequency (ml/min/1.73m2)
Normal                                      ≥80                         500 to 1,500 mg twice daily Mild                                        50-79                       500 to 1,000 mg twice daily Moderate                                    30-49                       250 to 750 mg twice daily Severe                                      < 30                        250 to 500 mg twice daily End-stage renal disease patients            -                           500 to 1,000 mg once daily (2) (1) undergoing dialysis
(1)
A 750 mg loading dose is recommended on the first day of treatment with levetiracetam.
(2)
Following dialysis, a 250 to 500 mg supplemental dose is recommended.

For children with renal impairment, levetiracetam dose needs to be adjusted based on the renal function as levetiracetam clearance is related to renal function. This recommendation is based on a study in adult renally impaired patients.

The CLcr in ml/min/1.73 m2 may be estimated from serum creatinine (mg/dl) determination, for young adolescents and children using the following formula (Schwartz formula): ks= 0.55 in Children to less than 13 years and in adolescent female; ks= 0.7 in adolescent male
Dosing adjustment for children and adolescents patients weighing less than 50 kg with impaired renal function:
Group                    Creatinine clearance                            Dose and frequency (ml/min/1.73m2)         Children from 4 years and adolescents weighing less than 50 kg Normal                   ≥80                    10 to 30 mg/kg (0.10 to 0.30 ml/kg) twice daily Mild                     50-79                  10 to 20 mg/kg (0.10 to 0.20 ml/kg) twice daily Moderate                 30-49                  5 to 15 mg/kg (0.05 to 0.15 ml/kg) twice daily Severe                   < 30                   5 to 10 mg/kg (0.05 to 0.10 ml/kg) twice daily End-stage renal disease --                       10 to 20 mg/kg (0.10 to 0.20 ml/kg) once daily (1) (2) patients undergoing dialysis
(1)
A 15 mg/kg (0.15 ml/kg) loading dose is recommended on the first day of treatment with levetiracetam.
(2)
Following dialysis, a 5 to 10 mg/kg (0.05 to 0.10 ml/kg) supplemental dose is recommended.

Hepatic impairment
No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the creatinine clearance may underestimate the renal insufficiency. Therefore a 50 % reduction of the daily maintenance dose is recommended when the creatinine clearance is < 60 ml/min/1.73 m2.

Paediatric population
The physician should prescribe the most appropriate pharmaceutical form, presentation and strength according to age, weight and dose.

Monotherapy
The safety and efficacy of Levebon 100 mg/ml in children and adolescents below 16 years as monotherapy treatment have not been established.
No data are available.

Add-on therapy for children aged 4 to 11 years and adolescents (12 to 17 years) weighing less than 50 kg
The initial therapeutic dose is 10 mg/kg twice daily.
Depending upon the clinical response and tolerability, the dose can be increased up to 30 mg/kg twice daily. Dose changes should not exceed increases or decreases of 10 mg/kg twice daily every two weeks. The lowest effective dose should be used.
Dose in children 50 kg or greater is the same as in adults.
Dose recommendations for children and adolescents:
Weight                        Starting dose:                                  Maximum dose: 10 mg/kg twice daily                            30 mg/kg twice daily
15 kg (1)                        150 mg twice daily                           450 mg twice daily (1)
20 kg                            200 mg twice daily                           600 mg twice daily
25 kg                            250 mg twice daily                           750 mg twice daily
(2)
From 50 kg                         500 mg twice daily                           1500 mg twice daily (1)
Children 25 kg or less should preferably start the treatment with Levetiracetam 100 mg/ml oral solution.
(2)
Dose in children and adolescents 50 kg or more is the same as in adults.

Add-on therapy for infants and children less than 4 years
The safety and efficacy of Levebon 100 mg/ml concentrate for solution for infusion in infants and children less than 4 years have not been established.
Currently available data are described in sections 4.8, 5.1, and 5.2 but no recommendation on a posology can be made.

Method of administration
Levebon 100 mg/ml concentrate is for intravenous use only and the recommended dose must be diluted in at least 100 ml of a compatible diluent and administered intravenously as a 15- minute intravenous infusion (see section 6.6).