Dosage & Administration

Adults and pediatric patients

Perampanel must be titrated, according to individual patient response, in order to optimize the balance between efficacy and tolerability. Perampanel should be taken orally once daily at bedtime or as prescribed by the physician. The physician should prescribe the most appropriate formulation and strength according to weight and dose.

 

Partial-Onset Seizures

Monotherapy or Adjunctive Therapy

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

Adults, adolescents age ≥ 12 years

Treatment with Perampanel 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, 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  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 should be titrated no more frequently than at 1-week intervals.

Children (from 4 to 11 years) weighing ≥ 30 kg

Treatment with Perampanel 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, 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  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 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 Perampanel 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 (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 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 should be titrated no more frequently than at 1 week intervals.

Children (from 4 to 11 years of age) weighing < 20 kg

Treatment with Perampanel 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 (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, 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  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 should be titrated no more frequently than at 1 week intervals.

 

Primary Generalized Tonic-Clonic Seizures

Adjunctive Therapy

Perampanel at a dose up to 8 mg/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 (12
years and older)
Children (7 – 11 years); weighing:
≥ 30 kg 20 – < 30 kg < 20 kg
Recommended
starting dose
2 mg/day (4 mL/day) 2 mg/day (4 mL/day) 1 mg/day (2 mL/day) 1 mg/day (2 mL/day)
Titration
(incremental steps)
2 mg/day (4 mL/day)
(no more
frequently than
weekly intervals)
2 mg/day (4 mL/day)
(no more
frequently than
weekly intervals)
1 mg/day (2 mL/day)
(no more
frequently than
weekly intervals)
1 mg/day (2 mL/day)
(no more
frequently than
weekly intervals)
Recommended
maintenance dose
Up to 8 mg/day (up to 16 mL/day) 4 – 8 mg/day (8-16 mL/day) 4 – 6 mg/day (8-12 mL/day) 2 – 4 mg/day (4-8 mL/day)
Titration
(incremental steps)
2 mg/day (4 mL/day)
(no more
frequently than
weekly intervals)
2 mg/day (4 mL/day)
(no more
frequently than
weekly intervals)
1 mg/day (2 mL/day)
(no more
frequently than
weekly intervals)
0.5 mg/day (1 mL/day)
(no more
frequently than
weekly intervals)
Recommended
maximum dose
12 mg/day (24 mL/day) 12 mg/day (24 mL/day) 8 mg/day (16 mL/day) 6 mg/day (16 mL/day)

Adults, adolescents age ≥ 12 years

Treatment with Perampanel 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) (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. Patients who are taking concomitant medicinal products that do not shorten the half-life of perampanel 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 should be titrated no more frequently than at 1-week intervals.

Children (from 7 to 11 years) weighing ≥ 30 kg

Treatment with Perampanel 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 (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, the dose may be increased by increments of 2 mg/day to 12 mg/day. Patients who are taking concomitant medicinal products that do not shorten the half life of perampanel, 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 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 Perampanel 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 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 should be titrated no more frequently than at 1 week intervals.

Children (from 7 to 11 years of age) weighing < 20 kg

Treatment with Perampanel 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  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 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 AEDs, 1 week for patients taking perampanel metabolism inducing AEDs, 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 perampanel in epilepsy did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Analysis of safety information in 905 perampanel-treated elderly patients (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.

 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 hemodialysis 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. Patients should be up-titrated using 2 mg 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 patients

The safety and efficacy of perampanel have not yet been established in children below 4 years of age in the POS indication or in children below 7 years of age in the PGTCS indication.


Method of administration

For oral use.

Perampanel should be taken as single oral dose at bedtime. It may be taken with or without food but preferably always under the same conditions. Switching between the tablet and suspension formulation should be done with caution.

Administration of Oral Suspension

Shake well before every administration. Use the provided adapter and graduated oral dosing syringe to administer the oral suspension. A household teaspoon or tablespoon is not an adequate measuring device. 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 adapter is in place. Discard any unused Perampanel (Fycompa) Oral Suspension three (3) months after first opening the bottle.

Instructions on how to use the oral dosing syringe and adapter.

  1. Shake for at least 5 seconds before use.
  2. Push down (1) and turn cap (2) to open bottle.
  3. Insert adaptor into the neck of the bottle until a tight seal is made.
  4. Push plunger of oral syringe completely down.
  5. Insert the oral syringe into the opening of the adaptor as far as possible.
  6. Turn upside down and withdraw the prescribed amount of Fycompa from the bottle.
  1. Turn upright and remove the oral syringe.
  2. Leave the adaptor in place and replace cap on bottle.
  3. After dose administration, separate barrel and plunger, and fully immerse both components in HOT soapy water.
  1. Immerse the barrel and plunger in water to remove any residual detergent, shake off excess water and leave components to air dry. Do not wipe dry the dispensers.
  1. Do not clean and reuse the syringe after 40 uses, or if the markings on the syringe wash off.