Posology : מינונים

4.2   Posology and method of administration

Posology
Fycompa must be titrated, according to individual patient response, in order to optimise the balance between efficacy and tolerability.
Perampanel should be taken orally once daily at bedtime. It may be taken with or without food.
The physician should prescribe the most appropriate formulation and strength according to weight and dose.

Switching between the tablet and suspension formulation should be done with caution (see section 5.2).

Partial Onset Seizures
Perampanel at doses of 4 mg/day to 12 mg/day has been shown to be effective therapy in partial-onset seizures.

The following table summarises the recommended posology for adults, adolescents and children from 4 years of age. More details are provided below the table.

Adult/adolescent                   Children (4 – 11 years); weighing: (12 years and
≥ 30 kg            20 - < 30 kg       < 20 kg older)
Recommended 2 mg/day                   2 mg/day           1 mg/day           1 mg/day starting dose (4 ml/day)               (4 ml/day)         (2 ml/day)         (2 ml/day) 2 mg/day           1 mg/day           1 mg/day
2 mg/day
(4 ml/day)         (2 ml/day)         (2 ml/day)
Titration        (4 ml/day)
(no more           (no more           (no more
(incremental     (no more frequently than    frequently than    frequently than steps)           frequently than weekly             weekly             weekly weekly intervals) intervals)         intervals)         intervals)
Recommended
4 – 8 mg/day               4 – 8 mg/day       4 – 6 mg/day       2 – 4 mg/day maintenance
(8 – 16 ml/day)            (8 – 16 ml/day)    (8 – 12 ml/day)    (4 – 8 ml/day) dose
2 mg/day           1 mg/day           0.5 mg/day
2 mg/day
(4 ml/day)         (2 ml/day)         (1 ml/day)
Titration        (4 ml/day)
(no more           (no more           (no more
(incremental     (no more frequently than    frequently than    frequently than steps)           frequently than weekly             weekly             weekly weekly intervals) intervals)         intervals)         intervals)
Recommended 12 mg/day                  12 mg/day          8 mg/day           6 mg/day maximum dose (24 ml/day)               (24 ml/day)        (16 ml/day)        (12 ml/day) 


Adults, adolescents age ≥ 12 years
Treatment with Fycompa should be initiated with a dose of 2 mg/day (4 ml/day). The dose may be increased based on clinical response and tolerability by increments of 2 mg (4 ml).
(either weekly or every 2 weeks, as per half-life considerations described below) to a maintenance dose of 4 mg/day (8 ml/day). to 8 mg/day (16 ml/day). Depending upon individual clinical response and tolerability at a dose of 8 mg/day (16 ml/day), the dose may be increased by increments of 2 mg/day (4 ml/day) to 12 mg/day (24 ml/day). Patients who are taking concomitant medicinal products that do not shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 2-week intervals. Patients who are taking concomitant medicinal products that shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 1-week intervals.

Children (from 4 to 11 years) weighing ≥ 30 kg
Treatment with Fycompa should be initiated with a dose of 2 mg/day (4 ml/day). The dose may be increased based on clinical response and tolerability by increments of 2 mg (4 ml/day) (either weekly or every 2 weeks as per half-life considerations described below) to a maintenance dose of 4 mg/day (8 ml/day) to 8 mg/day (16 ml/day). Depending upon individual clinical response and tolerability at a dose of 8 mg/day (16 ml/day), the dose may be increased by increments of 2 mg/day (4 ml/day) to 12 mg/day (24 ml). Patients who are taking concomitant medicinal products that do not shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 2-week intervals. Patients who are taking concomitant medicinal products that shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 1-week intervals.

Children (from 4 to 11 years of age) weighing 20 kg and < 30 kg
Treatment with Fycompa should be initiated with a dose of 1 mg/day (2 ml/day). The dose may be increased based on clinical response and tolerability by increments of 1 mg (2 ml/day) (either weekly or every 2 weeks as per half-life considerations described below) to a maintenance dose of 4 mg/day (8 ml/day) to 6 mg/day (12 ml/day). Depending upon individual clinical response and tolerability at a dose of 6 mg/day (12 ml/day), the dose may be increased by increments of 1 mg/day (2 ml/day) to 8 mg/day (16 ml/day). Patients who are taking concomitant medicinal products that do not shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 2-week intervals.
Patients who are taking concomitant medicinal products that shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 1-week intervals.

Children (from 4 to 11 years of age) weighing < 20 kg
Treatment with Fycompa should be initiated with a dose of 1 mg/day (2 ml/day). The dose may be increased based on clinical response and tolerability by increments of 1 mg (2 ml/day) (either weekly or every 2 weeks as per half-life considerations described below) to a maintenance dose of 2 mg/day (4 ml/day) to 4 mg/day (8 ml/day). Depending upon individual clinical response and tolerability at a dose of 4 mg/day (8 ml/day), the dose may be increased by increments of 0.5 mg/day (1 ml/day) to 6 mg/day (12 ml/day). Patients who are taking concomitant medicinal products that do not shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 2-week intervals.
Patients who are taking concomitant medicinal products that shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 1-week intervals.

Primary Generalised Tonic-Clonic Seizures
Perampanel at a dose up to 8 mg/day (16 ml/day) has been shown to be effective in primary generalised tonic clonic seizures.

The following table summarises the recommended posology for adults, adolescents and children from 7 years of age. More details are provided below the table.


Adult/adolescent              Children (7 – 11 years); weighing:
(12 years and
≥ 30 kg         20 - < 30 kg         < 20 kg older)
Recommended       2 mg/day             2 mg/day          1 mg/day          1 mg/day starting dose     (4 ml/day)           (4 ml/day)        (2 ml/day)        (2 ml/day) 2 mg/day          1 mg/day
2 mg/day                                                 1 mg/day
(4 ml/day)        (2 ml/day)
Titration         (4 ml/day)                                               (2 ml/day) (no more          (no more
(incremental      (no more                                                 (no more frequently than   frequently than steps)            frequently than                                          frequently than weekly            weekly weekly intervals)                                        weekly intervals) intervals)        intervals)
Recommended
Up to 8 mg/day       4 – 8 mg/day      4 – 6 mg/day      2 – 4 mg/day maintenance
(Up to 16 ml/day)    (8 – 16 ml/day)   (8 – 12 ml/day)   (4 – 8 ml/day) dose
2 mg/day          1 mg/day
2 mg/day                                                 0.5 mg/day
(4 ml/day)        (2 ml/day)
Titration         (4 ml/day)                                               (1 ml/day) (no more          (no more
(incremental      (no more                                                 (no more frequently than   frequently than steps)            frequently than                                          frequently than weekly            weekly weekly intervals)                                        weekly intervals) intervals)        intervals)
Recommended       12 mg/day            12 mg/day         8 mg/day          6 mg/day maximum dose      (24 ml/day)          (24 ml/day)       (16 ml/day)       (12 ml/day) 
Adults, adolescents age ≥ 12 years
Treatment with Fycompa should be initiated at a dose of 2 mg/day (4 ml/day). The dose may be increased based on clinical response and tolerability by increments of 2 mg (4 ml/day) (either weekly or every 2 weeks, as per half-life considerations described below) to a maintenance dose of up to 8 mg/day (16 ml/day). Depending upon individual clinical response and tolerability at a dose of 8 mg/day (16 ml/day), the dose may be increased up to 12 mg/day (24 ml/day), which may be effective in some patients (see section 4.4). Patients who are taking concomitant medicinal products that do not shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 2-week intervals.
Patients who are taking concomitant medicinal products that shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 1-week intervals.

Children (from 7 to 11 years) weighing ≥ 30 kg
Treatment with Fycompa should be initiated with a dose of 2 mg/day (4 ml/day). The dose may be increased based on clinical response and tolerability by increments of 2 mg (4 ml) (either weekly or every 2 weeks as per half-life considerations described below) to a maintenance dose of 4 mg/day (8 ml/day) to 8 mg/day (16 ml/day). Depending upon individual clinical response and tolerability at a dose of 8 mg/day (16 ml/day), the dose may be increased by increments of 2 mg/day (4 ml/day) to 12 mg/day (24 ml/day). Patients who are taking concomitant medicinal products that do not shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 2-week intervals. Patients who are taking concomitant medicinal products that shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 1-week intervals.


Children (from 7 to 11 years of age) weighing 20 kg and < 30 kg
Treatment with Fycompa should be initiated with a dose of 1 mg/day (2 ml/day). The dose may be increased based on clinical response and tolerability by increments of 1 mg (2 ml) (either weekly or every 2 weeks as per half-life considerations described below) to a maintenance dose of 4 mg/day (8 ml/day) to 6 mg/day (12 ml/day). Depending upon individual clinical response and tolerability at a dose of 6 mg/day, the dose may be increased by increments of 1 mg/day (2 ml/day) to 8 mg/day (16 ml/day). Patients who are taking concomitant medicinal products that do not shorten the half-life of perampanel (see 
section 4.5) should be titrated no more frequently than at 2-week intervals. Patients who are taking concomitant medicinal products that shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 1-week intervals.
o are taking concomitant medicinal products that do not shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 2-week intervals. Patients who are taking concomitant medicinal products that shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 1-week intervals.

Children (from 7 to 11 years of age) weighing < 20 kg
Treatment with Fycompa should be initiated with a dose of 1 mg/day (2 ml/day). The dose may be increased based on clinical response and tolerability by increments of 1 mg (2 ml) (either weekly or every 2 weeks as per half-life considerations described below) to a maintenance dose of 2 mg/day (4 ml/day) to 4 mg/day (8 ml/day). Depending upon individual clinical response and tolerability at a dose of 4 mg/day (8 ml/day), the dose may be increased by increments of 0.5 mg/day (1 ml/day) to 6 mg/day (12 ml/day). Patients who are taking concomitant medicinal products that do not shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 2-week intervals. Patients who are taking concomitant medicinal products that shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 1-week intervals.

Withdrawal
It is recommended that discontinuation be undertaken gradually to minimise the potential for rebound seizures. However, due to its long half-life and subsequent slow decline in plasma concentrations, perampanel can be discontinued abruptly if absolutely needed.

Missed doses
Single missed dose: As perampanel has a long half-life, the patient should wait and take their next dose as scheduled.

If more than 1 dose has been missed, for a continuous period of less than 5 half-lives (3 weeks for patients not taking perampanel metabolism-inducing anti-epileptic drugs (AED), 1 week for patients taking perampanel metabolism-inducing AEDs (see section 4.5)), consideration should be given to re-start treatment from the last dose level.

If a patient has discontinued perampanel for a continuous period of more than 5 half-lives, it is recommended that initial dosing recommendations given above should be followed.

Elderly (65 years of age and above)
Clinical studies of Fycompa in epilepsy did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Analysis of safety information in 905 perampanel-treated elderly subjects (in double-blind studies conducted in non-epilepsy indications) revealed no age-related differences in the safety profile. In combination with the lack of age-related difference in perampanel exposure, the results indicate that dose-adjustment in the elderly is not required. Perampanel should be used with caution in elderly taking into account the drug interaction potential in polymedicated patients (see section 4.4).

Renal impairment
Dose adjustment is not required in patients with mild renal impairment. Use in patients with moderate or severe renal impairment or patients undergoing haemodialysis is not recommended.

Hepatic impairment
Dose increases in patients with mild and moderate hepatic impairment should be based on clinical response and tolerability. For patients with mild or moderate hepatic impairment, dosing can be initiated at 2 mg (4 ml). Patients should be up-titrated using 2 mg (4 ml) doses no faster than every 2 weeks based on tolerability and effectiveness.

Perampanel dosing for patients with mild and moderate impairment should not exceed 8 mg.
Use in patients with severe hepatic impairment is not recommended.

Paediatric population
Fycompa is not indicated for the treatment of partial-onset seizures in pediatric patients under 4 years old

Fycompa is not indicated for the treatment of primary generalized tonic-clonic seizures in pediatric patients under 7 years old.
The safety and efficacy of Fycompa for the adjunctive treatment of partial-onset seizures in paediatric patients less than 4 years of age or for the adjunctive treatment of primary generalized tonic-clonic seizures in pediatric patients less than 7 years of age have not been established.

Method of administration

Fycompa Oral suspension
The press-in-bottle adapter (PIBA) which is supplied in the product carton should be inserted firmly into the neck of the bottle before use and remain in place for the duration of the usage of the bottle. The oral syringe should be inserted into the PIBA and the dose withdrawn from the inverted bottle. The cap should be replaced after each use. The cap fits properly when the PIBA is in place.
It may be taken with or without food. For Fycompa Oral suspension, the product should always be taken under the same conditions.


Fycompa film-coated tablets
Should be taken as single oral dose at bedtime. It may be taken with or without food (see section 5.2). The tablet should be swallowed whole with a glass of water. It should not be chewed, crushed or split. The tablets cannot be split accurately as there is no break line.