Dosing Considerations: Concomitant CYP3A Enzyme-Inducing AEDs Significantly Reduce Both Plasma Levels and Efficacy: Carbamazepine, oxcarbazepine and phenytoin all decrease mean FYCOMPA blood levels by approximately 50-70% and substantially decrease FYCOMPA efficacy. As there are no clinical trial data for FYCOMPA doses greater than 12 mg/day, there is insufficient information to recommend dose adjustments to correct for this.
Serious Aggression- and Hostility-Related Adverse Events: Closely monitor patients particularly during the titration period and at higher doses. FYCOMPA should be reduced if symptoms of aggression or hostility occur and should be discontinued immediately if symptoms are severe or worsening.
Recommended Dose and Dose Adjustment: Partial Onset Seizures: FYCOMPA at doses of 4 mg/day to 12 mg/day has been shown to be effective therapy in partial-onset seizures.
Treatment with FYCOMPA should be initiated with a dose of 2 mg/day. The dose may be increased based on clinical response and tolerability by increments of 2 mg to a maintenance dose of 4 mg/day to 8 mg/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.
In order to optimize the balance between efficacy and tolerability, FYCOMPA must always be titrated according to individual patient response.
FYCOMPA should be taken orally once daily at bedtime. The maximum recommended daily dose of FYCOMPA is 12 mg/day. Doses beyond 12 mg/day have not been studied in patients.
Primary Generalised Tonic-Clonic Seizures: FYCOMPA at a dose up to 8 mg/day has been shown to be effective in primary generalized tonic clonic seizures.
Treatment with FYCOMPA should be initiated at a dose of 2 mg/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 as follows) to a maintenance dose of up to 8 mg/day. Depending upon individual clinical response and tolerability at a dose of 8 mg/day, the dose may be increased up to 12 mg/day, which may be effective in some patients (see Precautions). Patients who are taking concomitant medicinal products that do not shorten the half-life of perampanel (see Interactions) 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 Interactions) should be titrated no more frequently than at 1-week intervals.
Adults: In the Presence of Enzyme-Inducing AEDs (EI-AEDs; carbamazapine, oxcarbazepine, phenytoin): The recommended starting dose of FYCOMPA in the presence of EI-AEDs, including carbamazepine, oxcarbazepine and phenytoin, is 4 mg/day. Based on clinical response and tolerability, the dose may be increased by increments of 2 mg to a maximum dose of 12 mg/day. Dose increases should occur no more frequently than at 1-week intervals.
Clinical trials revealed a lower efficacy in these patients at a given dose, compared to those not on enzyme-inducing AEDs. This is the result of lower FYCOMPA blood levels, suggesting that relatively higher doses would be needed in this patient population to achieve similar efficacy as those not on enzyme-inducing AEDs. However, there are no efficacy or safety data to support FYCOMPA doses beyond 12 mg/day, as they have not been studied in patients.
When these enzyme-inducing AEDs are introduced or withdrawn from a patient's treatment regimen, patient should be closely monitored for clinical response and tolerability. Dose adjustment of FYCOMPA may be necessary.
In the Absence of Enzyme-Inducing AEDs: Treatment with FYCOMPA should be initiated with a dose of 2 mg/day. The dose may be increased, based on clinical response and tolerability, by increments of 2 mg up to a dose of 8 mg/day. Dose increases should occur no more frequently than at 2-week intervals.
If FYCOMPA is well tolerated at 8 mg/day but clinical response is lacking, the dose may be increased by increments of 2 mg to 12 mg/day, depending upon individual clinical response and tolerability. The maximum recommended daily dose is 12 mg/day. In these patients, there was little difference in efficacy between 8 and 12 mg/day, while the proportion of patients with adverse events, including aggression/hostility-related increased.
Paediatrics population (below 12 years of age): The safety and efficacy of FYCOMPA in children below 12 years of age have not been established yet. No data are available.
Elderly Patients (≥ 65 years of age): Clinical studies of FYCOMPA did not include sufficient numbers of patients aged 65 and over to determine the safety and efficacy of FYCOMPA in the elderly population. Because of increased likelihood for adverse reactions in the elderly, dosage increases during titration are recommended no more frequently than every 2 weeks.
Patients with 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.
Patients with Hepatic Impairment: Dosage adjustment is recommended in patients with mild and moderate hepatic impairment, based on higher exposure and the longer half-life of FYCOMPA. The maximum recommended daily dose is 6 mg for patients with mild hepatic impairment and 4 mg for patients with moderate hepatic impairment. Starting dose should be 2 mg per day with increments of 2 mg every two weeks until target dose is achieved. Dose increases in patients with mild and moderate hepatic impairment, as with all patients, should be based on clinical response and tolerability. Use in patients with severe hepatic impairment is not recommended.
Missed Dose: Single missed dose: As FYCOMPA 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 FYCOMPA metabolism-inducing anti-epileptic drugs (AED), 1 week for patients taking FYCOMPA metabolism-inducing AEDs consideration should be given to restart treatment from the last dose level.
If a patient has discontinued FYCOMPA for a continuous period of more than 5 half-lives, it is recommended that initial dosing recommendations given in the previously mentioned text should be followed.
Discontinuing: When withdrawing, the dose should be gradually reduced. However, due to its long-half life and subsequent slow decline in plasma concentrations, FYCOMPA can be discontinued abruptly if absolutely needed.