Fycompa 2mg. 4mg. 6mg. 8mg. 10mg. 12mg FC tablet

Fycompa is indicated for the primary or adjunctive treatment of partial-onset seizures (POS) with or without secondarily generalised seizures in patients from 4 years of age and older. Fycompa is indicated for adjunctive treatment of primary generalised tonic-clonic (PGTC) seizures in patients from 7 years of age and older with idiopathic generalised epilepsy (IGE).

Posology
Fycompa must be titrated, according to individual patient response, in order to optimise the balance between efficacy and tolerability. Fycompa should be taken orally once daily at bedtime. The physician should prescribe the most appropriate formulation and strength according to weight and dose. Alternate formulations of Fycompa are available, including an oral suspension.

Partial-Onset Seizures (POS)
Monotherapy or adjunctive therapy
Fycompa 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:
u2265 30 kg
20 to < 30 kg
< 20 kg
Recommended starting dose
2 mg/day
2 mg/day
1 mg/day
1 mg/day
Titration (incremental steps)
2 mg/day (no more frequently than weekly intervals)
2 mg/day (no more frequently than weekly intervals)
1 mg/day (no more frequently than weekly intervals)
1 mg/day (no more frequently than weekly intervals)
Recommended maintenance dose
4-8 mg/day
4-8 mg/day
4-6 mg/day
2-4 mg/day
Titration (incremental steps)
2 mg/day (no more frequently than weekly intervals)
2 mg/day (no more frequently than weekly intervals)
1 mg/day (no more frequently than weekly intervals)
0,5 mg/day (no more frequently than weekly intervals)
Recommended maximum dose
12 mg/day
12 mg/day
8 mg/day
6 mg/day

Adults, adolescents age u2265 12 years
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 (either weekly or every 2 weeks as per half-life considerations described below) to a maintenance dose of 4 mg 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 medicines that do not shorten the half-life of perampanel (see section 4.5) should be titrated no more frequently than at 2-weeks intervals. Patients who are taking concomitant medicines 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 u2265 30 kg
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 (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 medicines 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 medicines 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 20 kg and < 30 kg
Treatment with Fycompa should be initiated with a dose of 1 mg/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 4 mg/day to 6 mg/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 to 8 mg/day. Patients who are taking concomitant medicines 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 medicines 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 < 20 kg
Treatment with Fycompa should be initiated with a dose of 1 mg/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 to 4 mg/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 to 6 mg/day. Patients who are taking concomitant medicines 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 medicines 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 (PGTC) Seizures
Adjunctive therapy
Fycompa 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:
u2265 30 kg
20 to < 30 kg
< 20 kg
Recommended starting dose
2 mg/day
2 mg/day
1 mg/day
1 mg/day
Titration (incremental steps)
2 mg/day (no more frequently than weekly intervals)
2 mg/day (no more frequently than weekly intervals)
1 mg/day (no more frequently than weekly intervals)
1 mg/day (no more frequently than weekly intervals)
Recommended maintenance dose
Up to 8 mg/day
4-8 mg/day
4-6 mg/day
2-4 mg/day
Titration (incremental steps)
2 mg/day (no more frequently than weekly intervals)
2 mg/day (no more frequently than weekly intervals)
1 mg/day (no more frequently than weekly intervals)
0,5 mg/day (no more frequently than weekly intervals)
Recommended maximum dose
12 mg/day
12 mg/day
8 mg/day
6 mg/day

Adults, adolescents age u2265 12 years
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 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 (see section 4.4). Patients who are taking concomitant medicines 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 medicines 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 u2265 30 kg
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 (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 medicines 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 medicines 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 20 kg and < 30 kg
Treatment with Fycompa should be initiated with a dose of 1 mg/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 4 mg/day to 6 mg/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 to 8 mg/day. Patients who are taking concomitant medicines 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 medicines 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 < 20 kg
Treatment with Fycompa should be initiated with a dose of 1 mg/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 to 4 mg/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 to 6 mg/day. Patients who are taking concomitant medicines 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 medicines 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 perampanelu2019s long half-life and subsequent slow decline in plasma concentrations, Fycompa 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 of Fycompa 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 medicines (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 Fycompa for a continuous period more than 5 half-lives, it is recommended that initial dosing recommendations given above should be followed.

Special populations
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. Fycompa should be used with caution in elderly taking into account the medicine interaction potential in polymedicated patients (see section 4.4).

Renal impairment
Dose adjustment is not required in patients with mild or moderate 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 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. Fycompa 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 Fycompa have not yet been established yet in children below 4 years of age in the POS indication or in children below 7 years of age in the PGTCS indication. No data are available.

Method of administration
Fycompa 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. To ensure the patient receives the entire dose the tablet should be swallowed whole without chewing or crushing.

Hypersensitivity to perampanel or to any of the excipients listed in section 6.1.

Suicidal ideation
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic medicine. The available data do not exclude the possibility of an increased risk for Fycompa. 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)
Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens u2013 Johnson Syndrome (SJS), which can be life-threatening or fatal, have been reported (frequency unknown; see section 4.8) in association with Fycompa 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. Symptoms of SJS include typically although not exclusively, skin detachment (epidermal necrosis/blister) < 10 %, erythematous skin (confluent), rapid progression, painful atypical target-like lesions and/or purpuric macules in wide dissemination or large erythema (confluent), bullous/erosive involvement of more than 2 mucous membranes. If signs and symptoms suggestive of these reactions appear, Fycompa should be withdrawn immediately, and an alternative treatment considered (as appropriate). If the patient has developed a serious reaction such as SJS or DRESS with the use of Fycompa, treatment with Fycompa must not be restarted in this patient at any time.

Absence and myoclonic seizures
Absence and myoclonic seizures are two common generalised seizure types that frequently occur in IGE patients. Other AEDs are known to induce or aggravate these seizure types. Patients with myoclonic seizures and absence seizures should be monitored while on Fycompa.

Nervous system disorders
Fycompa may cause dizziness and somnolence and therefore may influence the ability to drive or use machines (see section 4.7).

Hormonal contraceptives
At doses of 12 mg/day Fycompa may decrease the effectiveness of progestative-containing hormonal contraceptives; in this circumstance, additional non-hormonal forms of contraception are recommended when using Fycompa (see sections 4.5 and 4.6).

Falls
There is an increased risk of falls, particularly in the elderly.

Aggression
Aggressive and hostile behaviour have been reported in patients receiving Fycompa. 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. Homicidal ideation has been reported in patients. 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 Fycompa 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 Fycompa abuse.

Concomitant CYP3A inducing anti-epileptic medicines
Response rates after addition of Fycompa at fixed doses were less when patients received concomitant CYP3A enzyme-inducing anti-epileptic medicines (carbamazepine, phenytoin, oxcarbazepine) as compared to response rates in patients who received concomitant non-enzyme-inducing anti-epileptic medicines. Patientsu2019 response should be monitored when they are switching from concomitant non-inducer anti-epileptic medicines to enzyme inducing medicines and vice versa. Depending upon individual clinical response and tolerability, the dose may be increased or decreased 2 mg at a time (see section 4.2).

Other concomitant (non-anti-epileptic) cytochrome P450 inducing or inhibiting medicines
Patients should be closely monitored for tolerability and clinical response when adding or removing cytochrome P450 inducers or inhibitors, since Fycompa plasma levels can be decreased or increased; the dose of Fycompa may need to be adjusted accordingly.

Hepatotoxicity
Cases of hepatotoxicity (mainly hepatic enzyme increased) with Fycompa in combination with other anti-epileptic medicines have been reported. If hepatic enzymes elevation is observed, monitoring of liver function should be considered.

Excipients
Lactose intolerance: Fycompa contains lactose, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Fycompa.

Hormonal contraceptives
In healthy women receiving 12 mg for 21 days concomitantly with a combined oral contraceptive, Fycompa was shown to decrease the levonorgestrel exposure (mean C max and AUC values were each decreased by 40 %). Ethinylestradiol AUC was not affected by Fycompa 12 mg whereas C max was decreased by 18 %. Therefore, the possibility of decreased efficacy of hormonal progestative-containing contraceptives should be considered for women needing Fycompa 12 mg/day and an additional reliable method (intra-uterine device (IUD), condom) is to be used (see section 4.4).

Interactions between Fycompa and other anti-epileptic medicines
Potential interactions between Fycompa and other anti-epileptic medicines (AEDs) were assessed in clinical studies. A population PK analysis of three pooled Phase 3 studies in adolescent and adult patients with partial-onset seizures evaluated the effect of Fycompa (up to 12 mg once daily) on the PK of other AEDs. In another population PK analysis of pooled data from twenty Phase 1 studies in healthy subjects, with Fycompa up to 36 mg, and one Phase 2 and six Phase 3 studies in paediatric, adolescent, and adult patients with partial-onset seizures or primary generalised tonic-clonic seizures, with Fycompa up to 16 mg once daily, evaluated the effect of concomitant AEDs of perampanel clearance. The effect of these interactions on average steady state concentration is summarised in the following table.

AED co-administered
Influence of AED on Fycompa concentration
Influence of Fycompa on AED concentration
Carbamazepine
3-fold decrease
< 10 % decrease
Clobazam
No influence
< 10 % decrease
Clonazepam
No influence
No influence
Lamotrigine
No influence
< 10 % decrease
Levetiracetam
No influence
No influence
Oxcarbazepine
2-fold decrease
35 % increase
1) Phenobarbital (phenobarbitone)
20 % decrease
No influence
Phenytoin
2-fold decrease
No influence
Topiramate
20 % decrease
No influence
Valproic acid
No influence
< 10 % decrease
Zonisamide
No influence
No influence
1) Active metabolite monohydroxycarbazepine was not assessed.

Based on the results from the population pharmacokinetic analysis of patients with partial-onset seizures and patients with primary generalised tonic-clonic seizures the total clearance of Fycompa was increased when co-administered with carbamazepine (3-fold), and phenytoin or oxcarbazepine (2-fold), which are known inducers of enzymes of metabolism (see section 5.2). This effect should be taken into account and managed when adding or withdrawing these anti-epileptic medicines from a patientu2019s treatment regimen. Clonazepam, levetiracetam, phenobarbital, topiramate, zonisamide, carbamazepine, clobazam, lamotrigine and valproic acid did not affect to a clinically relevant manner the clearance of Fycompa. In a population pharmacokinetic analysis of patients with partial-onset seizures, Fycompa did not affect to a clinically relevant manner the clearance of clonazepam, levetiracetam, phenobarbital (phenobarbitone), phenytoin, topiramate, zonisamide, carbamazepine, clobazam, lamotrigine and valproic acid, at the highest Fycompa dose evaluated (12 mg/day). Fycompa was found to decrease the clearance of oxcarbazepine by 26 %. Oxcarbazepine is rapidly metabolised by cytosolic reductase enzyme to the active metabolite, monohydroxycarbazepine. The effect of Fycompa on monohydroxycarbazepine concentrations is not known. Fycompa is dosed to clinical effect regardless of other AEDs.

Effect of Fycompa on CYP3A substrates
In healthy subjects, Fycompa (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 Fycompa doses cannot be excluded. (See section 4.4).

Effect of cytochrome P450 inducers on Fycompa pharmacokinetics
Strong inducers of cytochrome P450, such as rifampicin and hypericum, are expected to decrease perampanel concentrations and the potential for higher plasma concentrations of the reactive metabolites in their presence could not be excluded. Felbamate has been shown to decrease the concentrations of some medicines and may also reduce Fycompa concentrations.

Effect of cytochrome P450 inhibitors on Fycompa 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 Fycompa 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, Fycompa (4 mg once daily for 19 days) had no effect on C max or AUC of levodopa.

Alcohol
The effects of Fycompa on complex tasks involving alertness and vigilance such as driving ability were additive or supra-additive to the impairment effects of alcohol itself, as found in a pharmacodynamic interaction study in healthy subjects. Multiple dosing of Fycompa 12 mg/day increased levels of anger, confusion, and depression as assessed using the Profile of Mood State 5-point rating scale (see section 5.1). These effects may also be seen when Fycompa 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 adolescent patients age u2265 12 years and children age 4 to 11 years, there were no notable differences compared to the adult population.

Safety in pregnancy and lactation has not been established. Women of childbearing potential and contraception in males and females
Fycompa is not recommended in women of childbearing potential not using contraception. Fycompa may decrease the effectiveness of progestative-containing hormonal contraceptives. An additional non-hormonal form of contraception is, therefore recommended (see sections 4.4 and 4.5).

Pregnancy
There are limited amounts of data (less than 300 pregnancy outcomes) from the use of perampanel in pregnant women. Studies in animals did not indicate any teratogenic effects in rats or rabbits, but embryotoxicity was observed in rats at maternally toxic doses (see section 5.3). Fycompa is not recommended during pregnancy.

Breastfeeding
Studies in lactating rats have shown excretion of perampanel and/or its metabolites in milk (for details see section 5.3). It is not known whether perampanel is excreted in human milk. A risk to the newborns/infants cannot be excluded. Fycompa is not recommended during breastfeeding.

Fertility
In the fertility study in rats, prolonged and irregular oestrous cycles were observed at high-dose (30 mg/kg) in females; however, these changes did not affect the fertility and early embryonic development. There were no effects on male fertility (see section 5.3). The effect of Fycompa on human fertility has not been established.

Fycompa may impair the patientu2019s ability to drive and use machines. Fycompa may cause dizziness and somnolence. Patients are advised not to drive a vehicle, operate machinery or engage in other potentially hazardous activities until it is known whether Fycompa affects their ability to perform these tasks (see sections 4.4 and 4.5).

Summary of safety profile
In all controlled and uncontrolled trials in patients with partial-onset seizures, 1 639 subjects have received Fycompa of whom 1 147 have been treated for 6 months and 703 for longer than 12 months. In the controlled and uncontrolled trials in patients with primary generalised tonic-clonic seizures, 114 subjects have received Fycompa 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 event was 1,7 %, 4,2 % and 13,7 % in patients randomised to receive Fycompa at the recommended doses of 4 mg, 8 mg and 12 mg/day, respectively, and 1,4 % in patients randomised to receive placebo. The adverse events most commonly (u2265 1 % in the total Fycompa group and greater than placebo) leading to discontinuation were dizziness and somnolence. In the controlled Phase 3 primary generalised tonic-clonic seizures clinical trial, the rate of discontinuation as a result of an adverse reaction was 4,9 % in patients randomised to receive Fycompa 8 mg, and 1,2 % in patients randomised to receive placebo. The adverse reaction most commonly leading to discontinuation (u2265 2 % in the Fycompa group and greater than placebo) was dizziness.

Post-marketing experience
The following adverse reactions have been identified during post approval use of Fycompa.

Skin and subcutaneous tissue disorders: Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS) (see section 4.4).

Tabulated summary of adverse reactions
In the table below, adverse reactions were identified based on review of the full Fycompa clinical studies safety database. The following convention has been used for the classification of adverse reactions: very common (u2265 1/10), common (u2265 1/100 to < 1/10), uncommon (u2265 1/1 000 to < 1/100), rare (u2265 1/10 000 to < 1/1 000), very rare (< 10 000), not known (cannot be estimated from the available data). Within each frequency category, adverse reactions are presented in order of decreasing seriousness.

System Organ Class
Very common
Common
Uncommon
Not known
Metabolism and nutrition disorders
Decreased appetite, increased appetite
Psychiatric disorders
Aggression, anger, anxiety, confusional state
Suicidal ideation, suicide attempt, hallucinations
Nervous system disorders
Dizziness, somnolence
Ataxia, dysarthria, balance disorder, irritability
Eye disorders
Diplopia, vision blurred
Ear and labyrinth disorders
Vertigo
Gastrointestinal disorders
Nausea
Skin and subcutaneous tissue disorders
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)*, Stevens u2013 Johnson Syndrome (SJS)*
Musculoskeletal and connective tissue disorders
Back pain
General disorders and administrative site conditions
Gait disturbance, fatigue
Investigations
Weight increased
Injury, poisoning and procedural complications
Fall

* See section 4.4.

Paediatric population
Based on the clinical trial database of 196 adolescents exposed to Fycompa from double-blind studies for partial onset seizures and primary generalised tonic-clonic seizures, the overall safety profile in adolescents was similar to that of adults, except for aggression, which was observed more frequently in adolescents than in adults. Based on the clinical trial database of 180 paediatric patients exposed to Fycompa from a multicentre, open label study, the overall safety profile in children was similar to that established for adolescents and adults, except for somnolence, irritability, aggression, and agitation which were observed more frequently in the paediatric study compared to studies in adolescents and adults. Available data in children did not suggest any clinically significant effects of Fycompa on growth and development parameters including body weight, height, thyroid function, insulin-like growth factor-1 (IGF-1) level, cognition (as assessed by Aldenkamp-Baker neuropsychological assessment schedule (ABNAS)), behaviour (as assessed by Child Behaviour Checklist (CBCL)), and dexterity (as assessed by Lafayette Grooved Pegboard Test (LGPT)). However, long term effects (greater than 1 year) on learning, intelligence, growth, endocrine function, and puberty in children remain unknown.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

There have been post-marketing cases of intentional and accidental overdose in paediatric patients with doses of Fycompa up to 36 mg and in adult patients with doses up to 300 mg. The adverse reactions observed included altered mental status, agitation, aggressive behaviour, coma and depressed level of consciousness. The patients recovered without sequelae. There is no available specific antidote to the effects of Fycompa. 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 Fycompa could be prolonged. Because of low renal clearance special interventions such as forced diuresis, dialysis or haemoperfusion are unlikely to be of value.