Fycompa 2mg Eisai Medicines for Supplementing Corruption (2 blisters x 14 tablets)

Dosage form Box of 2 blisters x 14 tablets
Specifications Perampanel

Ingredient

Composition informationContent
Perampanel2mg

Uses

indications

Fycompa drugs are indicated in the following cases:

  • Treatment of supplementary sperm sperm on the localities with or without secondary mension epilepsy in adults and children aged 12 years and older with epilepsy.

    ATC code: N03AX22.

    Mechanism of action

    Perampanel is the first substance in the group (First-in-Class) selected, non-competitive antagonistic, ionotropic receptor α-amino-3-tydroxy-5-methyl-4-iSoxazoleProproprife (AMPA) glutamate on the post-synap nerve cell after synap. Glutamat is a main stimulant neurotransmitter in the central nervous system and is related to many neurological disorders caused by excessive stimulation of neurons. The activation of AMPA receptors because glutamat is thought to be responsible for most rapid transmission stimulating through the Synap in the brain. In In Vitro studies, Perampanel is not competing with AMPA to connect with the AMPA receptor, but the cohesion of Perampanel has been pushed out by non -competitive AMPA receptors, indicating that Perampanel is an non -competitive AMPA receptor counterclose. In vitro, Perampanel inhibits the increase in intracellular calcium caused by AMPA (which is not caused by NMDA). In Vivo, Perampanel significantly extends the delay of seizures in a epilepsy model caused by AMPA.

    The exact mechanism for Perampanel to promote anti -epileptic effects on humans still need to be completely clarified.

    Pharmacological effect

    A pharmacokinetic - pharmacokinetic analysis (in terms of efficiency) has been conducted based on the data contributed from three tests on effectiveness for local start -up seizures. In addition, a pharmacokinetics analysis (about efficiency) has been conducted in an effective test for spastic spastic seizures - convulsions. In both analysis, the use of Perampanel is correlated with a decrease in the frequency of epilepsy.

    Mental mental performance. Single and multi -dose of 8 mg and 12 mg reduces mental performance in healthy volunteers related to the dose. The impact of Perampanel on complex tasks such as driving ability is plus or united with the effect of reducing alcohol. Check the mental mental performance back to the original level within 2 weeks from the stop use of Perampanel.

    Cognitive function. In a study in healthy volunteers to assess Perampanel's influence on alertness and memory by using a set of evaluation standards, no effect of Perampanel was found after the single and multi -doses of Perampanel up to 12 mg/day.

    alertness and mood. The degree of alertness decreases in the form of dosage related to healthy objects that are used for Perampanel 4 - 12 mg/day. When the color worsens only after the dose of 12 mg/day; Changes in lightweight mood and reflect the overall alert reduction. Use multi -dose Perampanel 12 mg/day also increases the effects of alcohol on vigilance and alertness and increases the level of anger, confusion and depression according to the evaluation of the 5 -point assessment of the mood stat state.

    Heart physiological electrophysiology. Perampanel does not extend the adjustment range of QT (QTC) when used in daily dose of up to 12 mg/day and has no clinical or important dose or clinical effects on QRS period.

    Clinical efficiency and safety

    Local seizures

    The effectiveness of Fycompa for local spaces has been determined in 3 trials, random, double blindness, control with placebo, multicolored treatment center for 19 weeks in adult and teenagers. Subjects who have had a localized seizure, have or not fully transmitized and are not fully controlled by 1-3 anti -epileptic drugs (AED) simultaneously. In the first period of 6 weeks, subjects need more than 5 seizures without any time without epilepsy more than 25 days. In these 3 tests, the subjects had an average period of epilepsy about 21.06 years. From 85.3% to 89.1% of patients taking 2-3 anti -epileptic drugs at the same time, with or no treatment simultaneously by stimulating the vagus nerve.

    Two studies (research 304 and 305) compare the dose of Fycompa 8 and 12 mg/day with placebo and a third study (306 research) compares the dose of Fycompa 2, 4 and 8 mg/day with placebo. In all three tests, after an initial period of 6 weeks to set the frequency of epilepsy before random selection, the objects are randomly selected and increased the dose to the random dose. In the dose adjustment phase in all 3 tests, the treatment is started at a dose of 2 mg/day and increases each week with an increase of 2 mg/day until the target dose.

    Objects have unwanted effects that cannot be tolerated, may still use the same dosage or reduce the dose to the previous tolerate dose. In all 3 tests, the dose adjustment period is followed by a 13 -week maintenance period, of which patients are maintained with a stable Fycompa dose.

    The combination rate of people responds 50% is 19% with a placebo group, 29% for a group using 4 mg, 35% for groups using 8 mg and 35% for a group using 12 mg. A statistically significant influence on a 28 -day epilepsy decrease (from the beginning to the treatment stage) when compared to the placebo group that was observed with Fycompa treatment at 4 mg/day (research 306), 8 mg/day (research 304, 305 and 306) and 12 mg/day (research 304 and 305). The percentage of people who meet 50% in groups using 4 mg, 8 mg and 12 mg respectively is 23.0%, 31.5% and 30.0% respectively when Perampanel is used in combination with anti -epilepsy drugs that cause enzyme induction and 33.3%, 46.5% and 50.0% when Perampanel is used in combination with anti -epileptic drugs without enzyme induction. These studies show that the use of Perampanel at the dose of 4 mg to 12 mg, once a day is significantly more effective than placebo, in the form of supplementary treatment in this patient group.

    Data from control studies with placebo shows improvement in the control of seizures that have been observed with the dose of Fycompa 4 mg once a day and this benefit has been enhanced when increasing the dose to 8 mg/day. Do not observe the benefits of effectiveness at 12 mg compared to the dose of 8 mg in a group of patients in general. The benefit of a 12 mg dose is observed in some 8 mg tolerances and when clinically responded to that dose is not enough. A clinical decrease in the frequency of epilepsy compared to the placebo has been achieved early in the second week of drug use when the patient reaches daily dose 4 mg.

    1.7 - 5.8% of patients taking Perampanel in clinical studies did not have epilepsy during the maintenance period of 3 months compared to 0% -1.0% of patients who use fake patients without any data on the effect of anti -epileptic drugs used simultaneously to achieve Perampanel.

    Research and expansion of open labels

    97% of patients who complete random trials in patients with localized seizures have been put into research to expand open labels (n = 1186). Patients from random tests are transferred to Perampanel for 16 weeks, followed by a long -term maintenance stage ≥ 1 year). The average daily dose is 10.05 mg.

    Sexicular seizure - Scratching all the first development

    Fycompa in the form of complementary treatment for patients 12 years of age and older is bitten by a whole epilepsy through spastic spastic seizures - the elementary convulsions have been established in a multi -centered study, random, double blind, control with placebo (research 332). Patients who are eligible to take a stable dose of 1-3 anti -epileptic drugs undergoing at least 3 spastic spasms - convulsions of the whole first phase in the first period of 8 weeks are randomly selected in the group using Fycompa or placebo. The research group includes 164 patients (Fycompa n = 82, placebo n = 82). Patients are adjusted for 4 weeks to 8 mg target daily dose or the highest tolerance and be treated for 13 weeks with the final dose reaching at the end of the dose titration period. The total treatment time is 17 weeks. Research drugs have been used once a day.

    The percentage of people who responded 50%for spastic seizures - convulsions of the whole first phrase in the maintenance phase in the Perampanel group (58.0%) significantly higher than in the placebo group (35.8%), P = 0.0059. The percentage of 50% respondents is 22.2% when Perampanel is used in combination with anti -epilepsy drugs that cause enzyme induction and 69.4% when Perampanel is used in combination with anti -epileptic drugs that do not cause enzyme induction. The number of objects using Perampanel and is taking anti -epilepsy drugs causing enzyme induction is small (n = 9). Change the average percentage on the frequency of spastic spastic epilepsy of the whole primary stream every 28 days in the willow titration period and the maintenance stage (combined) compared to before the larger random selection with Perampanel (-76.5%) than the placebo (-38.4%), P

    Other forms of allococcal seizures

    Perampanel's effectiveness and safety in patients with muscle vibration seizures have not been determined. The existing data is not enough to make any conclusions.

    Perampanel's effectiveness in treating unproven seizures.

    In the study of 332, in patients with spastic spastic seizures - the whole of primary elementary convulsions (PGTC), who also had a sperm seizure at the same time, 16.7% (4/24) patients using Perampanel did not have seizures compared to 13.0% (3/23) patients with placebo. In patients with conscious epilepsy at the same time, 22.2% (6/27) Patients using Perampanel have no seizures compared to 12.1% (4/33) patients use placebo.

    23.5% (August 191) Patients who use Perampanel do not have all seizures compared to 4.9% (4/81) patients use placebo.

    The stage of research and expansion of open labels

    Of the 140 subjects completed research 332, 114 subjects (81.4%) have gone into the expansion research phase. Random test patients are transferred to Perampanel for 6 weeks, followed by a long -term maintenance period (1 year). During the expansion research phase, 73.7% of the daily -doses of Perampanel dose is greater than 4 - 8 mg/day and 16.7% with daily doses greater than 8-12 mg/day. The reduction of the frequency of spastic spastic epilepsy - a whole of primary convulsions (PGTC) at least 50% was observed at 65 9% of subjects after 1 year of treatment during the expansion research phase (compared to the frequency of their initial epilepsy before using Perampanel). These data are suitable for the data that changes the percentage of epilepsy frequency and shows that the percentage of people who meet 50% of the epilepsy - convulsions of the whole first is often stable over time from the 26th week to the end of the 2nd year. The similar results are observed when all seizures and seizures are absent from awareness compared to the seizure of the seizures as evaluated over time.

    switch to monomers

    There is no data on the effect of stopping anti -epilepsy drugs simultaneously to achieve Perampanel.

    Group of children's patients

    The European Pharmaceutical Management Agency (EMA) has postponed the obligation to submit the research results with Fycompa at one or more children's subgroups for anti -treatment epilepsy (epilepsy syndrome associated with their localities and epilepsy syndrome (see the dose, usage for information about use in teenagers).

    Three key, double-blind studies, lying them with placebo 3, including 143 teenagers aged 12-18. The results in these teenagers are similar to the observed results in adult patients.

    Research 332 includes 22 teenagers 12-18 years old. The results in these teenagers are similar to the observed results in adult patients.

    Perampanel's pharmacokinetics

    absorption

    After drinking, Perampanel is easily absorbed without evidence that this substance has metabolized through the liver significantly. Food does not affect the level of absorption but slows down the absorption speed. When used with food, the peak concentration in plasma decreases and is 1 hour later than the medication when changing.

    distribution

    Data from In vitro studies show that Perampanel binds about 95% to plasma protein.

    In vitro studies show that Perampanel is not a significant substrate or inhibitor of organic polypeptides (OATP) IB1 and IB3, organic anion (O all, 2, 3 and 4, organic cations (OCT) 1, 2, and 3, and 3, and p-Glycoprotein and anti-cancer proteins (BCRP).

    Biological metabolism

    Perampanel is strongly metabolized through the original oxidation and glucuronids. The initial oxidation metabolism through the intermediate of CYP3A is based on the results of In vitro studies using CYP enzymes of recombinant and human liver microsom.

    However, this transformation has not been completely explained and other roads cannot be excluded.

    After using Perampanel with radioactive markers, only a small amount of Perampanel metabolites have been observed in plasma.

    Elimination

    After taking a dose of Perampanel with radioactive marks for 8 healthy elderly, 30% of the recovered radiation has been found in urine and 70% in feces. In urine and feces, the recovered radioactive amount mainly includes a mixture of oxidative metabolites and conjugated metabolites. In a population pharmacokinetics analysis, including data from 19 phase 1 studies, Perampanel's average news is 105 hours.

    When used in combination with carbamazepin is a strong CYP3A induction drug, the average news is 25 hours.

    linear/non -linear

    In healthy objects, Perampanel's concentration in plasma increases proportional to the dose range from 2-12 mg. In a population pharmacokinetics analysis in patients with localized sperm epilepsy using Perampanel up to 12 mg/day and patients with spastic spasms - Flagical convulsions use Perampanel up to 8 mg/day in clinical trials that are controlled to placebo, linear relationship between dose and perampanel concentration in plasma has been recorded.

    Special patient groups

    Hepatic failure

    Perampanel's pharmacokinetics after a single dose of 1 mg has been evaluated in 12 mild and medium-level liver failures (type A and B, according to the corresponding right) compared to 12 healthy people suitable for demographic. Perampanel's average apparent clearance is not cohesive in mild liver failure objects of 188 ml/minute compared to 338 ml/minute at appropriate controls, and in average liver failure objects of 120 ml/minute compared to 392 ml/min at appropriate controls. TU2 is longer in mild liver failure objects (306 hours compared to 125 hours) and average liver failure objects (295 hours compared to 139 hours) compared to suitable healthy subjects.

    kidney failure

    Perampanel's

    pharmacokinetics has not been officially evaluated in patients with renal failure.

    Perampanel is eliminated almost only through metabolism, followed by the rapid secretion of metabolites; Only a small amount of Perampanel metabolites are observed in plasma. In a population pharmacokinetics analysis in patients with local sperm epilepsy with creatinine clearance in the range of 39 - 160 ml/minute and using Perampanel up to 12 mg/day in clinical trials that are controlled to placebo, Perampanel clearance is not affected by creatinine clearance. In a population pharmacokinetics analysis in patients with spastic spastic seizures - First -level convulsions using Fycompa up to 8 mg/day in clinical research with a place of placebo, Perampanel's clearance is not affected by the initial creatinine clearance.

    Gender

    In a population pharmacokinetic analysis in patients with local bleeding epilepsy using Perampanel up to 12 mg/day and patients with spastic spasms - convulsions of the whole primary primary use of Perampanel up to 8 mg/day in clinical tests that are controlled with placebo, Perampanel's clearance in women is 18% (0.54 liters/hour) lower than in men (0.66 liters/hour).

    Elderly (65 years or older)

    In a population pharmacokinetics analysis in patients with local starting epilepsy (ages 12 - 74 years old) and spastic spastic seizures - a whole of primary convulsions (aged 12 - 58 years old) and use Perampanel up to 8 or 12 mg/day in clinical trials that have control over the placebo, do not observe significant influence of age to Perampanel's clearance. No need to consider adjusting the dose in the elderly (see the dose, usage).

    Group of children's patients

    In a population pharmacokinetic analysis in teenagers in phase 3 clinical studies, there is no noticeable difference between this group of patients and the general group.

    Research on drug interaction

    Interrogen interaction assessment

    Inhibition of drug metabolic enzyme

    In human liver microsom, Perampanel (30 mol/l) has a weak inhibitory effect on CYP2C8 and UGT1A9 among the main cyt and UGT enzymes of the liver.

    Type metabolic enzyme induction

    Compared to positive control drugs (including Phenobarbital, Rifampicin), Perampanel has been found to cause weak induction CYP2B6 (30 umol/l) and CYP3A4/5 E 3 Umol/L) among the main cyp and UGT enzymes of the liver in cultured liver cells.

  • Before taking Fycompa 2mg Eisai Medicines for Supplementing Corruption (2 blisters x 14 tablets)

    How to use

    should take Fycompa as a single dose before going to bed. Can be used with or not with food (see pharmacokinetics). Should swallow the whole tablet with a glass of water. Do not chew, crush or divide the pill. It is impossible to divide the pills exactly because there is no lines. To ensure adequate dose, need to drink whole tablets without chewing or crushing.

    Dosage

    adults and adolescents aged 12 and older

    Need to adjust Fycompa dose according to the response of each patient to optimize the balance between efficiency and tolerance.

    Should drink Perampanel once a day before going to bed.

    Local sperm epilepsy

    Perampanel at a dose of 4 mg/day to 12 mg/day has been shown to be effective for local boundary seizures.

    Should start the starting dose of Fycompa 2 mg/day. It is possible to increase the dose based on clinical response and tolerance for each increase of 2 mg (per week or every 2 weeks, according to the considering the sale time described below) to the maintenance dose of 4 mg/day - 8 mg/day.

    Depending on the clinical response and the ability to tolerate each individual at a dose of 8 mg/day, the dose may increase by increasing the amount of 2 mg/day to 12 mg/day. The patient is taking the drugs simultaneously without shortening the sale time of Perampanel (see the interaction) should be adjusted to the dose more often than the 2 -week distance. The patient is taking the drugs while shortening the sale time of Perampanel (see the interaction) should be adjusted to the dose more often than the 1 -week distance.

    Sexicular seizures - First -level convulsions

    Perampanel at a dose of up to 8 mg/day has been shown to be effective in spastic seizures - convulsions of the whole primary.

    Should start the starting dose of Fycompa 2 mg/day. The dose can be increased based on clinical response and tolerance capacity for each increase of 2 mg (per week or every 2 weeks, according to the considering the sale time described below) to the maintenance dose of up to 8 mg/day. Depending on the clinical response and the ability to tolerate each individual at a dose of 8 mg/day, the dose can be increased to 12 mg/day that can be effective in some patients (see the warning and caution when using the drug). The patient is taking the drugs simultaneously without shortening the sale time of Perampanel (see the interaction) should be titrated as not frequent than at a distance of 2 weeks. The patient is taking the drugs while shortening the sale time of Perampanel (see the interaction) should be titrated than the dose more often than at a distance of 1 week.

    When stopping using Fycompa, the dose should be slowly reduced (see the warning and caution when using the drug).

    Elderly (65 years and older)

    Clinical studies on Fycompa in epilepsy have not included whether the number of subjects aged 65 and over to determine whether they have a different response than the younger subjects. Analysis of safety information on 905 elderly people treated with Perampanel (in double blind studies conducted on non -epileptic indications) shows that there is no age -related difference in safety data. Combined with no age difference in the use of Perampanel, the results showed that it was not necessary to adjust the dose in the elderly. Perampanel needs to be used cautiously in the elderly due to the ability to interact with drugs in patients who use a lot of drugs (see the warning and caution when using the drug).

    kidney failure

    Unsurting dose adjustment in mild renal impairment patients. It is not recommended to use in patients with average renal impairment or severe renal failure or patients who are being bloody.

    liver failure

    Increasing dose in patients with mild and medium liver failure should be based on clinical response and tolerance. For patients with mild or medium liver failure, the dose may be started at a dose of 2 mg. The dose should be adjusted with 2 mg, not faster every 2 weeks based on tolerance and efficiency.

    Perampanel dose for patients with mild and moderate liver failure must not exceed 8 mg.

    Do not recommend the use in patients with severe liver failure.

    Group of children's patients

    The safety and effectiveness of Perampanel in children under 12 years of age has not been determined. There is no data.

    Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What do

    do when using overdose? In an intentional overdose report that could lead to a dose of up to 264 mg, a patient had events about mental changes, agitation, aggression and recovery without sequelae.

    There is currently no specific antidote to the effect of Perampanel. General support for patients includes monitoring of survival signs and observing the patient's clinical status. Due to the long selling time of the drug, the effects caused by Perampanel can last. Due to low kidney clearance, special interventions such as mandatory diuretic, hemolysis or uncertainty blood transfusion.

    In case of emergency, call the 115 emergency center immediately or go to the nearest local health station.

    What to do when forgetting 1 dose?

    If you forget more than 1 dose, for a period of less than 5 semi -waste cycles (3 weeks for patients who do not use anti -epileptic drugs that cause perampanel metabolism, 1 week for patients using anti -epileptic drugs that cause perampanel metabolism (see interactive part), should consider to start treating treatment from the last dose.

    If the patient has stopped using Perampanel for a continuous time of more than 5 semi -waste cycles, it is recommended to comply with the recommendations on the starting dose mentioned above.

    Add dose as soon as you remember. However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double doses to compensate for missed dose.

    Side Effects

    When using Fycompa, you may experience unwanted effects (ADR) such as:

    Summary of safety records

    In all tests with control and uncontrolled in patients there are local starting epilepsy. 1639 patients used Perampanel, of which 1147 patients were used for 6 months and 703 patients were used for more than 12 months.

    In control and non -control tests in patients with spastic spastic seizures - all -primary convulsions, 114 subjects used Perampanel, of which 68 subjects were used for 6 months and 36 subjects used for more than 12 months.

    Unwanted effects lead to stopping treatment:

    In clinical trials with a 3rd phase control of local starting epilepsy, the percentage of treatment as a result of an unwanted effect is 1.7%, 4.2% and 13.7% in patients who are randomly selected to use Perampanel at the recommended dose of 4 mg, 8 mg and 12 mg/day, according to the corresponding sense, and 1.4% in patients who are randomly selected to use. The most common unwanted effects (> 1% in the entire Perampanel group and larger than the placebo group) leads to the stop treatment of dizziness and drowsiness

    In clinical trials that have a 3 -phase control of the seizure seizures of the whole progressive, the rate of stopping treatment as a result of an unwanted effect of 4.9% in patients who are randomly selected to use Perampanel 8 mg and 1.2% in randomly selected patients to use placebo. The most unwanted unwanted effect leads to treatment stop (≥ 2% in the Perampanel group and is larger than the fake group) is dizzy.

    List of unwanted effects

    In the table below, unwanted effects, have been determined based on evaluation of the safety database of full clinical studies on Fycompa, listed in organ systems and frequency. The initial assessment was conducted by considering all unwanted effects that appeared in treatment (TEEE) in double -phase blind studies on epilepsy that occurred in> 2% of patients in the entire Fycompa group. The following unwanted effects are also considered: the incidence is higher than the placebo; severity, severity and treatment rate due to unwanted effects; Analysis of drug use and dosage response; And the homogeneity with Fycompa's pharmacological properties. Unwanted effects that appear in treatment occur at less frequency and meet the same standards as for unwanted effects that appear in more common treatment are also considered. The following convention has been used to classify unwanted effects: very common ≥ 1/10), common (1/100 to

    The dose of 2 mg/day has not been put into this assessment because this dose is not considered an effective dose and the ratio of unwanted effects to appear in treatment (TEEE) in the group the dose is equivalent or lower than the Teae ratio in the placebo group.

    In each frequency group, unwanted effects are presented in the order of severity.

    Agency group system is very common

    Increase your appetite

    Anger

    Anxiety

    Confusion state

    Self -committed thoughts

    Try to commit suicide

    Sleepy

    Air conditioning loss

    Language disorder

    balance disorders

    easily stimulated

    blurred vision

    Concluding

    Tired

    Based on the clinical database of 165 teenagers, the frequency, type and severity of unwanted effects in teenagers are expected to be similar to adults.

    Instructions on how to handle ADR:

    Notify the physician the unwanted effects when using the drug.

    Warnings

    Before using the drug you need to read the instructions carefully and refer to the information below.

    Contraindicated

    Fycompa drug contraindicated in the following cases:

  • Hypersensitivity to active ingredients or any excipients in the drug.
  • Be cautious when using

    need to be very careful when taking the drug for patients in the following cases:

    suicide thought

    suicide thoughts and suicidal behavior have been reported in patients treated with anti -epileptic drugs in some indications. A comprehensive analysis of random tests that are controlled to placebo on anti -epileptic drugs has also shown a slight increase in the risk of suicide thoughts and suicide behavior. The mechanism of this risk is unknown and existing data does not exclude the possibility of increasing risk to Perampanel.

    Therefore, it is necessary to monitor patients on signs of suicide thoughts, suicide behaviors and appropriate treatment. It is necessary to advise patients (and patient care) to seek medical advice if the signs of suicide thoughts appear or suicide behavior.

    Central nervous system disorders

    Perampanel can cause dizziness and drowsiness, so it can affect the ability to drive or operate machinery (see the effect of the drug on the ability to drive and operate machinery).

    Oral contraceptives

    At 12 mg/day, Fycompa can reduce the effectiveness of hormone contraceptives containing progesterone; In this case, it is recommended to use additional methods of contraception without hormones when using Fycompa (see interactive section).

    End of treatment

    recommend that the stopping of the drug should be done slowly to minimize the possibility of an corresponding seizure (see the use, dose). However, due to the long -term semi -discharged time and plasma concentrations decreased slowly later, it is possible to stop Perampanel when it is really necessary.

    falls

    may increase the risk of falling, especially in the elderly; unknown cause.

    aggression

    The act of causing him and hostile has been reported in patients treated with Perampanel. In patients treated with Perampanel in clinical trials, aggression, anger and discomfort that have been reported more often at higher doses. Most of the unwanted effects are reported to be mild or medium levels and the patient recovers or by adjusting the dose. However. The thought of harming others, physical attacks or threatened acts has been observed in some patients ( Abuse of drugs

    Be careful in patients with a history of drug abuse and need to monitor patients on Perampanel abuse symptoms.

    Anti -epilepsy drug causes CYP 3A touch simultaneously

    The response ratio after additional perampanel at a fixed dose is less when the patient is taken with anti -epileptic drugs that cause enzyme CYP3A (carbamazepin, phenytoin, oxcarbazepine) and when compared to the response ratio in patients with anti -epileptic drugs that do not cause simultaneous enzyme induction. It is necessary to monitor the response of patients when they are converted from anti -epileptic drugs without causing enzyme -used induction simultaneously to anti -epileptic drugs that cause enzyme induction and vice versa. Depending on the clinical response and tolerance of each individual, the dose may increase or decrease by 2 mg at a time (see the usage, dose).

    Other drugs that cause induction or inhibition of Cytochrom P450 are simultaneously used (in addition to anti -epileptic drugs)

    Patients should be closely monitored for their ability to tolerate and clinically respond when extra or eliminate induction or Cytochrom P450 inhibitors, because the Perampanel concentration in plasma can be supervised or increased; Perampanel dose may be adjusted.

    Fycompa contains lactose, so patients with genetic problems have galactose intolerance, lactase deficiency or glucose - galactose should not be used.

    The effect of the drug on driving and operating machinery

    Fycompa has a moderate effect on the ability to drive and operate machinery.

    Perampanel can cause dizziness and drowsiness, so it can affect the ability to drive or operate machinery. It is necessary to advise patients not to drive, operate complicated machines or participate in other dangerous activities until they know how Perampanel affects their ability to perform these jobs (see the warning and cautious part when using the drug and the interaction).

    Use drugs for women during pregnancy and lactation

    Women are likely to be pregnant and contraception in men and women

    It is not recommended to use Fycompa in women who are likely to get pregnant without using contraception unless they are really necessary.

    Pregnant women

    The amount of data is limited (less than 300 pregnancy results) from the use of Perampanel in pregnant women. Animal studies do not show any teratogenic effect in rats and rabbits, but toxicity to the embryo has been observed in rats with toxic doses for mother animals. Do not recommend using fycompa during pregnancy.

    breastfeeding

    Studies in breastfeeding mice have shown all the perampanel and/or its metabolites in the milk. It is not clear whether Perampanel will be excreted in breast milk.

    cannot rule out the risk for babies/young children. Must decide to stop breastfeeding or stop/avoid treatment with Fycompa, need to consider the benefits of breastfeeding for children and the benefits of treatment for the mother.

    Reproduction

    In a study of fertility in rats, prolonged and irregularly observed sex cycle has been observed in high doses (30 mg/kg) on ​​Cai rats, however, these changes do not affect fertility and early stage embryo development. There is no effect on the fertility of male rats. The influence of Perampanel on the fertility of people has not been determined.

    Interactive drug

    Fycompa is not considered a strong induction drug or a strong Cytochrom P450 or UGT enzyme (see pharmacokinetics).

    Oral contraceptives

    In healthy women using 12 mg Fycompa (not 4 mg/day or 8 mg/day) for 21 days simultaneously with a oral contraceptive pills, Fycompa has shown to reduce the level of levonorgestrel (CMAX values ​​(the highest concentration in plasma) and AUC (the area below the curved) average each type decreased by 40%). The AUC of EthinyleLestradiol is not affected by Fycompa 12 mg while CMAX decreased by 18%. Therefore, it is advisable to consider the ability to reduce the effectiveness of oral contraceptives containing progestatif for women who need to use Fycompa 12 mg/day and should use a reliable contraceptive additional method of supplementation (uterine equipment (IUD), condoms) (see the warning and cautious part when using the drug).

    Interaction between Fycompa and other anti -epileptic drugs

    The ability to interact between Fycompa (up to 12 mg once daily) and other anti -epileptic drugs (AED) have been assessed in clinical and evaluation studies in the pharmacokinetic analysis of 4 -phase -3 -phase -phase studies including patients with local sperm sperm and spastic seizures - total convulsions. The influence of these interactions on the average concentration in a stable state is summarized in the following table.

    anti -epileptic drugs (AED as simultaneously) The effect of anti -epileptic drugs on the concentration of fycompa The influence of fycompa on anti -epileptic drug concentration Clobazam does not affect decreased

    levetiracetam does not affect does not affect

    oxcarbazepin decreased 1.9 times Discount 35%1) Influence does not affect phenytoin decreased 1.7 times does not affect

    topiramat decreased by 19% without influence Enjoy Discount

    Some anti -epileptic drugs are known as enzyme -induced drugs (carbamazepin, phenytoin, oxcarbazepin) that shows Perampanel's clearance and thus reduces the concentration of perampanel in plasma.

    Carbamazepin, a strongly known enzyme -induced drug, reduces two -thirds of Perampanel concentration in a study conducted on healthy objects.

    A similar result was observed in a population pharmacokinetic analysis in patients with localized epilepsy using Perampanel up to 12 mg/day and patients with spastic epilepsy - convulsions of the whole primary primary use of Perampanel up to 8 mg/day in clinical trials that are controlled with placebo. The total clearance of Fycompa increases when used with carbamazepin (2.75 times), phenytoin (1.7 times) and oxcarbazepine (1.9 times) are the known drugs that cause drug metabolic enzymes (see pharmacokinetic part). This effect should be taken into account and treated when adding or withdrawing these anti -epileptic drugs from the patient's treatment regimen.

    In a population pharmacokinetic analysis in patients with local start -up epilepsy using Fycompa up to 12 mg/day in clinical trials that are controlled with placebo, Fycompa does not affect clinically the clearance of Clonazepam, Levetiracetam, Phenobarbital, Phenytoin, Topiramat, Zonisamid, Carbamidin, Carbazepin, Carbazepin, Carbazepin, Carbazepin, Carbazirin, Carbazirin, Carbazirin, Carbazirin, Carbazirin, Carbazam Lamotrigin and Valproic acid at the highest perampanel dose have been evaluated (12 mg/day).

    In a municoning analysis of epilepsy, Perampanel reduced the clearance of 26%oxcarbazepi. Oxcarbazepine is rapidly metabolized by cytosolic reductase enzyme into an active metabolic substance, monohydroxycarbazepine. The influence of perampanel on monohydroxycarbazepine concentration is not known.

    Perampanel is used for clinical effects regardless of other anti -epileptic drugs (AED).

    Effect of Perampanel on substrates of CYP3A

    In healthy subjects, Fycompa (6 mg once a day for 20 days) has reduced the AUC of Midazolam 13%. Midazolam concentration is not eliminated (or other sensitive CYP3A4 substrates) with higher fycompa dose.

    The effect of the drug causing Cytochrom P450 on the pharmacokinetics of Perampanel

    Strong drugs Cytochrom P450, like Rifampicin and Hypericum, are expected to reduce Perampanel's concentration. Felbamat has been shown to reduce the concentration of some drugs and can also reduce Perampanel's concentration.

    The effect of the Cytochrom P450 inhibitors on Perampanel's dynamics

    In healthy subjects, Ketoconazole (400 mg once a day for 10 days) is a CYP3A4 inhibitor that increased the AUC of Perampanel by 20% and extended the waste time of Perampanel 15% (67.8 hours compared to 58.4 hours). It is impossible to eliminate greater effects when Perampanel is combined with a CYP3A inhibitor with a longer selling time than ketoconazole or when the inhibitor is used during longer treatment. Strong inhibitors of other ISOforms of Cytochrom P450 may also be likely to increase Perampanel levels.

    Levodopa: In healthy subjects, Fycompa (4 mg once a day for 19 days) does not affect CMAX or AUC of Levodopa.

    alcohol

    A dynamic interaction study in healthy subjects has shown the effects of Perampanel on jobs related to alertness and vigilance as the ability to drive is a combination or co -effect with the impact of alcohol. Use multi -dose Perampanel 12 mg/day to increase the level of anger, confusion and depression as evaluated by using the data of the 5 -point assessment of the mood state (see the pharmacological part).

    These effects can also be observed when Fycompa is used in combination with other antidepressants acting on the central nervous system (CNS).

    Group of children's patients

    Research on drug interaction is only done in adults.

    In a population pharmacokinetic analysis in teenagers in phase 3 clinical studies, there is no noticeable difference between this group of patients and the general group.

    Storage

    Leave a cool place, avoid light, temperatures below 30⁰C.

    To be out of reach of children, read the instructions carefully before use.

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