Posology : מינונים

4.2. Posology and method of administration
Posology
Adults
The recommended starting dose of cenobamate is 12.5 mg per day, titrated gradually to the recommended target dose of 200 mg per day. Based on clinical response, dose may be increased to a maximum of 400 mg per day.
The recommended titration schedule is provided in table 1, which should not be exceeded because of the potential for serious adverse reactions (see section 4.8).

Table 1: Recommended dosage in adults with focal-onset seizures in epilepsy Treatment phase              Dose (per day, oral)               Duration 12.5 mg                            Weeks 1 and 2
Treatment initiation
25 mg                              Weeks 3 and 4
50 mg                              Weeks 5 and 6
Titration                          100 mg                             Weeks 7 and 8 150 mg                             Weeks 9 and 10
Weeks 11 and 12 and
Target dose                        200 mg onwards
Some patients, who do not reach optimal seizure control, may benefit from doses above 200 mg (increased by increments of
Dose optimisation
50 mg/day every two weeks) up to a maximum of 400 mg daily.

Missed doses
If patients miss one dose, it is recommended that they take a single dose as soon as they remember, unless it is less than 12 hours until their next regularly scheduled dose.

Discontinuation
It is recommended that discontinuation be undertaken gradually to minimise the potential for rebound seizures (i.e. over at least 2 weeks), unless safety concerns require abrupt withdrawal.

Elderly (65 years of age and above)
Clinical studies of cenobamate did not include sufficient numbers of subjects aged 65 and over, to determine whether they responded differently from younger patients. It has been reported that elderly subjects on antiepileptic medicinal products have higher incidence of adverse reactions such as fatigue, gait disturbance, fall, ataxia, balance disorder, dizziness and somnolence. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic or renal function and of concomitant disease as well as the potential interactions in polymedicated patients (see section 4.4).

Renal impairment
Cenobamate should be used with caution and reduction of the target dose may be considered in patients with mild to moderate (creatinine clearance 30 to <90 ml/min) or severe (creatinine clearance < 30 ml/min) renal impairment. The maximum recommended dose for patients with mild, moderate, or severe renal impairment is 300 mg/day. Cenobamate should not be used in patients with end-stage renal disease or patients undergoing haemodialysis.

Hepatic impairment
Exposure to cenobamate was increased in patients with chronic hepatic disease. A change in the starting dose is not required; however, a decrease in target doses of up to 50% may need to be considered. The maximum recommended dose in patients with mild and moderate hepatic impairment is 200 mg/day. Cenobamate should not be used in patients with severe hepatic impairment.

Paediatric population
The safety and efficacy of Xcopri in children aged 0 months to 18 years have not yet been established. No data are available.

Method of administration
Oral use.
Cenobamate should typically be taken once daily as single oral dose at any time. However, it should preferably be taken at the same time each day. It may be taken with or without food (see section 5.2).
The tablet should be swallowed with a glass of water. The tablets cannot be split accurately as there is no break line and the accuracy of the dose cannot be ensured.
The tablets can be crushed. The crushed tablet can be mixed with water and administered by mouth as an oral suspension, as described below.

Administration of Crushed Tablets by Mouth as Oral Suspension
1) Crush the appropriate number of tablet(s) for the prescribed dose.
2) In a cup, combine the crushed tablet(s) and 25 mL of water.
3) Swirl to suspend the crushed tablet(s).
4) Drink the suspension immediately. Do not store the tablet-water mixture for later use.
5) To ensure no tablet residue is left in the container, rinse the container with 25 mL of water and drink.
6) Visually confirm that no particles are left in the container. If particles remain, repeat step 5.