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  • Fycompa
    / Megapharm


    Active Ingredient
    Perampanel 2, 4, 6, 8, 10, 12 mg.

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    7 X 2 mg

    partial basket chart 51056 6529

    Film Coated Tablets

    28 X 4 mg

    partial basket chart 51057 6530

    Film Coated Tablets

    28 X 6 mg

    partial basket chart 51058 6531

    Film Coated Tablets

    28 X 8 mg

    partial basket chart 51059 6532

    Film Coated Tablets

    28 X 10 mg

    partial basket chart 51053 6527

    Film Coated Tablets

    28 X 12 mg

    partial basket chart 51055 6528

    Related information


    Dosage

    Posology
    Adults and adolescents: The drug 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.
    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. Treatment with Perampanel 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 (either weekly or every 2 weeks, as per half-life considerations described below) 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. 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 8 mg/day has been shown to be effective in primary generalised tonic clonic seizures. Treatment with Perampanel 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 below) 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 .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. 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, 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 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.
    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. 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 population: The safety and efficacy of perampanel in children below 12 years of age have not been established yet. No data are available.
    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. The tablets cannot be split accurately as there is no break line. To ensure the patient receives the entire dose the tablets should be swallowed whole without chewing or crushing.


    Indications

    Indicated for the adjunctive treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy aged 12 years and older. Indicated for the adjunctive treatment of primary generalized tonic-clonic seizures in patients with epilepsy aged 12 years and older with idiopathic generalized epilepsy.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients.


    Special Precautions

    Suicidal ideation: Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic medicinal products in several indications. A meta-analysis of randomised placebo-controlled trials of anti-epileptic medicinal products has also shown a small increased risk of suicidal ideation and behaviour. 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 behaviours 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.
    Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS): Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported (frequency unknown; see section 4.8) in association with perampanel treatment.
    At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. Symptoms of DRESS include typically, although not exclusively, fever, rash associated with other organ system involvement, lymphadenopathy, liver function tests abnormalities and eosinophilia. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If signs and symptoms suggestive of these reactions appear, perampanel should be withdrawn immediately and an alternative treatment considered (as appropriate).
    Nervous system disorders: Perampanel may cause dizziness and somnolence and therefore may influence the ability to drive or use machines.
    Oral contraceptives: At doses of 12 mg/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.
    End of treatment: 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.
    Falls: There appears to be an increased risk of falls, particularly in the elderly; the underlying reason is unclear.
    Aggression: 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.
    Abuse potential: Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of perampanel abuse.
    Concomitant CYP 3A inducing anti-epileptic medicinal products: Response rates after addition of perampanel at fixed doses were less when patients received concomitant CYP3A enzyme-inducing anti-epileptic medicinal products (carbamazepine, phenytoin, oxcarbazepine) as compared to response rates in patients who received concomitant 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 2 mg 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.
    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.
    See prescribing information for full details.


    Side Effects

    Dizziness, somnolence, decreased appetite, increased appetite, aggression, anger, anxiety, confusional state, ataxia, dysathria, balance disorder, irritability, diplopia, vision blurred, vertigo, nausea, back pain, gait disturbance, fatigue, weight increased, fall.
    See prescribing information for full details.


    Drug interactions

    Perampanel is not considered a strong inducer or inhibitor of cytochrome P450 or UGT enzymes.
    Oral contraceptives: In healthy women receiving 12 mg (but not 4 or 8 mg/day) for 21 days concomitantly with a combined oral contraceptive, Perampanel was shown to decrease the levonorgestrel exposure (mean Cmax and AUC values were each decreased by 40%). Ethinylestradiol AUC was not affected by Perampanel 12 mg whereas Cmax was decreased by 18%. Therefore, the possibility of decreased efficacy of progestative-containing oral contraceptives should be considered for women needing Perampanel 12 mg/day and an additional reliable method (intra-uterine device (IUD), condom) is to be used.
    Effect of perampanel on CYP3A substrates: In healthy subjects, Perampanel (6 mg once daily for 20 days) decreased midazolam AUC by 13%. A larger decrease in exposure of midazolam (or other sensitive CYP3A substrates) at higher Perampanel doses cannot be excluded.
    Effect of cytochrome P450 inducers on perampanel pharmacokinetics: Strong inducers of cytochrome P450, such as rifampicin and hypericum, are expected to decrease perampanel concentrations. Felbamate has been shown to decrease the concentrations of some drugs and may also reduce perampanel concentrations. The potential for higher plasma concentrations of the reactive metabolites in presence of strong cytochrome P450 inducers could not be excluded.
    Effect of cytochrome P450 inhibitors on perampanel pharmacokinetics: In healthy subjects, the CYP3A4 inhibitor ketoconazole (400 mg once daily for 10 days) increased perampanel AUC by 20% and prolonged perampanel half-life by 15% (67.8 h vs 58.4 h). Larger effects cannot be excluded when perampanel is combined with a CYP3A inhibitor with longer half-life than ketoconazole or when the inhibitor is given for a longer treatment duration. Levodopa. In healthy subjects, Perampanel (4 mg once daily for 19 days) had no effect on Cmax or AUC of levodopa.
    Alcohol: 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 pharmacodynamic interaction study in healthy subjects. Multiple dosing of perampanel 12 mg/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.
    Paediatric population: Interaction studies have only been performed in adults. In a population pharmacokinetic analysis of the adolescent patients in the Phase 3 clinical studies, there were no notable differences between this population and the overall population.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: Perampanel is not recommended in women of childbearing  age or during pregnancy due to limited amounts of data from the use of perampanel in pregnant women.
    Breastfeeding: It is not known whether perampanel is excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Fycompa therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
    Fertility: The effect of perampanel on human fertility has not been established.


    Overdose

    There is limited clinical experience with perampanel overdose in humans. In a report of an intentional overdose that could have resulted in a dose up to 264 mg, the patient experienced events of altered mental status, agitation and aggressive behaviour and recovered without sequelae. There is no available specific antidote to the effects of perampanel. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. In view of its long half-life, the effects caused by perampanel could be prolonged. Because of low renal clearance special interventions such as forced diuresis, dialysis or haemoperfusion are unlikely to be of value.


    Important notes

    Lactose: this drug contains lactose.
    Meals: may be taken with or without food.
    Should not be chewed, crushed or split, the tablet should be swallowed whole with a glass of water.


    Manufacturer
    Eisai Inc.
    Licence holder
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