Fycompa® (generic name: perampanel) is indicated for the adjunctive treatment of partial-onset seizures with or without secondarily generalised seizures in patients with epilepsy aged 12 years and older.
Fycompa® is indicated for the adjunctive treatment of primary generalised tonic-clonic seizures in adult and adolescent patients from 12 years of age with idiopathic generalised epilepsy.
Film-coated tablets containing 2mg & 4mg perampanel.
Adults and adolescents
Perampanel 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 before bedtime.
Partial Onset Seizure
Perampanel at doses of 4mg/day to 12mg/day has been shown to be effective therapy in partial-onset seizures.
Treatment with perampanel should be initiated with a dose of 2mg/day. The dose may be increased based on clinical response and tolerability by increments of 2mg/day to a maintenance dose of 4mg/day to 8mg/day. Depending upon individual clinical response and tolerability at dose of 8mg/day, the dose may be increased by increments of 2mg/day to 12mg/day. The maximum recommended daily dose is 12mg. 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 Generalised Tonic-Clonic Seizures
Perampanel at a dose up to 8mg/day has been shown to be effective in primary generalised tonic-clonic seizures.
Treatment with perampanel should be initiated with a dose of 2mg/day. The dose may be increased based on clinical response and tolerability by increments of 2mg/day to a maintenance dose of 8mg/day to 12mg/day. Depending upon individual clinical response and tolerability at dose of 8mg/day, the dose may be increased by increments of 2mg/day to 12mg/day. The maximum recommended daily dose is 12 mg. 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.
When withdrawing perampanel, the dose should be gradually reduced. However, due to its long half-life, and subsequent slow decline in plasma concentrations, perampanel can be discontinued abruptly if absolutely needed.
Paediatric population below 12 years of age
The safety and efficacy of perampanel in children below 12 years of age have not been established yet. No data are available.
Elderly (65 years of age and above)
Clinical studies of perampanel 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 patients.
Method of Administration
Perampanel should be taken as single oral dose at bedtime. It may be taken with or without food. The tablet should be swallowed whole with a glass of water. It should not be chewed, crushed or split.
Hypersensitivity to the active substance or to any of the excipients.
Special Warnings and Precautions for Use
Suicidal ideation and behavior have been reported in patients treated with anti-epileptic agents including perampanel. A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products has also shown a small increased risk of suicidal ideation and behavior. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for perampanel.
Therefore patients should be monitored for signs of suicidal ideation and behaviors and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
Perampanel may cause dizziness and somnolence and therefore may influence the ability to drive or use machines.
There appears to be an increased risk of falls, particularly in the elderly; the underlying reason is unclear and may in part be related to the underlying diseases studied.
Aggressive and hostile behaviour has been reported in patients receiving perampanel therapy. In perampanel-treated patients in clinical trials, aggression, anger and irritability were reported more frequently at higher doses. Most of the reported events were either mild or moderate and patients recovered either spontaneously or with dose adjustment. However, thoughts of harming others, physical assault or threatening behaviour were observed in some patients (<1% in perampanel clinical studies). Patients and caregivers should be counselled to alert a healthcare professional immediately if significant changes in mood or patterns of behaviour are noted. The dosage of perampanel should be reduced if such symptoms occur and should be discontinued immediately if symptoms are severe.
Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of perampenal abuse.
Perampanel contains lactose, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or
glucose-galactose malabsorption should not take this medicine.
Fycompa® is not recommended in women of childbearing potential.
Fycompa® is not recommended during pregnancy.
Interaction with other medicinal products and other forms of interaction
Perampanel is not considered a strong inducer or inhibitor of cytochrome P450 or UGT enzymes.
At doses of 12mg/day perampanel may decrease the effectiveness of progestative-containing hormonal contraceptives; in this circumstance additional non-hormonal forms of contraception are recommended when using perampanel.
Concomitant CYP3A inducing anti-epileptic medicinal products
Response rates after addition of perampanel at fixed doses were lower when patients received concomitant CYP3A enzyme-inducing anti-epileptic medicinal products (carbamazepine, phenytoin, oxcarbazepine) as compared to response rates in patient who received concomitant non-enzyme–inducing anti-epileptic medicinal products. The 50% responder rates in the 4mg, 8mg and 12mg groups were respectively 23.0%, 31.5%, and 30.0% in combination with enzyme-inducing anti-epileptic medicinal products, and were 33.3%, 46.5% and 50.0% when perampanel was given in combination with non-enzyme-inducing anti-epileptic medicinal products. Patient’s response should be monitored when they are switching from concomitant non-inducer anti-epileptic medicinal products to enzyme-inducing medicinal products and vice versa. Depending upon individual clinical response and tolerability, the dose may be increased or decreased 2mg at a time.
Other concomitant (non- anti-epileptic) cytochrome P450 inducing or inhibiting medicinal products
Patients should be closely monitored for tolerability and clinical response when adding or removing cytochrome P450 inducers or inhibitors, since perampanel plasma levels can be decreased or increased; the dose of perampanel may need to be adjusted accordingly.
The effects of perampanel on tasks involving alertness and vigilance such as driving ability were additive or supra-additive to the effects of alcohol itself, as found in a pharmacodynamics interaction study in healthy subjects. Multiple dosing of perampanel 12mg/day increased levels of anger, confusion, and depression as assessed using the Profile of Mood State 5-point rating scale. These effects may also be seen when perampanel is used in combination with other central nervous system (CNS) depressants.
Summary of safety profile
In all controlled and uncontrolled trials in patients with partial-onset seizures, 1639 subjects have received perampanel of whom 1147 have been treated for 6 months and 703 for longer than 12 months.
In the controlled and uncontrolled trial in patients with primary generalized tonic-clonic seizures, 114 subjects have received perampanel of whom 68 have been treated for 6 months and 36 for longer than 12 months. Adverse reactions leading to discontinuation:
In the controlled Phase 3 partial-onset seizures clinical trials, the rate of discontinuation as a result of an adverse reaction was 1.7%, 4.2% and 13.7% in patients randomized to receive perampanel at the recommended doses of 4mg, 8mg and 12mg/day, respectively,
and 1.4% in patients randomized to receive placebo. The adverse reactions most commonly (≥1% in the total perampanel group and greater than placebo) leading to discontinuation were dizziness and somnolence.
In the controlled Phase 3 primary generalized tonic-clonic seizures clinical trial, the rate of discontinuation as a result of an adverse reaction was 4.9% in patients randomized to receive perampanel 8mg, and 1.2% in patients randomized to receive placebo. The adverse reaction most commonly leading to discontinuation (≥ 2% in the perampanel group and greater than placebo) was dizziness.
Tabulated list of adverse reactions
In the table below, adverse reactions, which were identified based on review of the full Fycompa® clinical studies safety database, are listed by system organ class and frequency. The initial review was done by considering all treatment emergent adverse events (TEAEs) in the double-blind Phase 3 epilepsy studies that occurred in ≥2% of patients in the total Fycompa® group. The following were also considered: incidence rates higher than with placebo; severity, seriousness, and rates of discontinuation due to the events; analyses of exposure and dose-response; and consistency with Fycompa® pharmacology. TEAEs that occurred in less frequency and met the same criteria as for the more frequent TEAEs were also considered. The following convention has been used for the classification of adverse reactions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000).
The dose of 2mg/day was not included in this assessment because it is not considered to be an effective dose, and the rates of TEAEs in that dose group were generally comparable to, or lower than, those in the placebo group.
Within each frequency category, adverse reactions are presented in order of decreasing seriousness.
Based on the clinical trial database of 165 adolescents, the frequency, type and severity of adverse reactions in adolescents are expected to be the same as in adults.
For further product information kindly refer to the prescribing information.
Fycompa® package insert.
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