Composition, form of production and packaging
The tablets covered with a film cover of orange color, round, biconcave, with engraving "Р„ 275" on one side and "2" on the other side.
1 tab.
perrampanel 2 mg
Excipients: lactose monohydrate - 78.5 mg, low-substituted giprolose - 14 mg, povidone - 5 mg, magnesium stearate - 0.5 mg.
The composition of the film shell: opadray orange - 5 mg (hypromellose 2910 - 56%, talc - 28%, macrogol 8000 - 10%, titanium dioxide - 4%, iron dye oxide yellow - 1.8%, iron-oxide red-0.2%).
7 pcs. - blisters (1) - packs of cardboard.
The tablets covered with a film cover of red-orange color, round, biconcave, with engraving "Р„ 277" on one side and "4" on the other side.
1 tab.
perrampanel 4 mg
Excipients: lactose monohydrate - 157 mg, low-substituted giprolose - 28 mg, povidone - 10 mg, magnesium stearate - 1 mg.
The composition of the film shell: opadray red - 10 mg (hypromellose 2910 - 56%, talc - 28%, macrogol 8000 - 10%, titanium dioxide - 4%, iron-oxide red oxide - 2%).
14 pcs. - blisters (2) - packs of cardboard.
The tablets covered with a film cover of pink color, round, biconcave, with engraving "Р„ 294" on one side and "6" on the other side.
1 tab.
perrampanel 6 mg
Excipients: lactose monohydrate - 151 mg, low-substituted giprolose - 18 mg, povidone - 10 mg, microcrystalline cellulose - 14 mg, magnesium stearate - 1 mg.
The composition of the film shell: opadrai pink - 10 mg (hypromellose 2910 - 56%, talc - 25%, macrogol 8000 - 10%, titanium dioxide - 8.6%, iron oxide red oxide - 0.4%).
14 pcs. - blisters (2) - packs of cardboard.
The tablets covered with a film cover of gray-pink color, round, biconcave, with engraving "Р„ 295" on one side and "8" on the other side.
1 tab.
perrampanel 8 mg
Excipients: lactose monohydrate 149 mg, low-substituted giprolose 18 mg, povidone 10 mg, microcrystalline cellulose 14 mg, magnesium stearate 1 mg.
The composition of the film shell: opadrai magenta - 10 mg (hypromellose 2910 - 56%, talc - 29.4%, macrogol 8000 - 10%, titanium dioxide - 4%, iron dye red oxide - 0.4%, ferric oxide black oxide - 0.2%).
14 pcs. - blisters (2) - packs of cardboard.
The tablets covered with a film cover of gray-green color, round, biconcave, with engraving "Р„ 296" on one side and "10" on the other side.
1 tab.
perrampanel 10 mg
Excipients: lactose monohydrate - 147 mg, low-substituted giprolose - 18 mg, povidone - 10 mg, microcrystalline cellulose - 14 mg, magnesium stearate - 1 mg.
The composition of the film shell: opadray green - 10 mg (hypromellose 2910 - 50.9%, talc - 24%, macrogol 8000 - 9.1%, titanium dioxide - 8%, iron dye oxide yellow - 1.5%, indigo carmine - 6.5%).
14 pcs. - blisters (2) - packs of cardboard.
The tablets covered with a film cover of blue color, round, biconcave, with engraving "Р„ 297" on one side and "12" on the other side.
1 tab.
perrampanel 12 mg
Excipients: lactose monohydrate 145 mg, low-substituted giprolose 18 mg, povidone 10 mg, microcrystalline cellulose 14 mg, magnesium stearate 1 mg.
The composition of the film shell: opadray blue - 10 mg (hypromellose 2910 - 50.9%, talc - 25.5%, macrogol 8000 - 9.1%, titanium dioxide - 8%, indigo carmine - 6.5%).
14 pcs. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Mechanism of action
Perampanel is the first in its class selective non-competitive antagonist of ionotropic? -amino-3-hydroxy-5-methyl-4-isoxazolepropionate- (AMPA) glutamate receptors on postsynaptic neurons.
Glutamate is the main stimulating neurotransmitter in the central nervous system, which plays an important role in the pathogenesis of a number of neurological diseases caused by overexcitation of neurons.
It is assumed that the activation of AMPA receptors by glutamate is responsible for the fastest exciting synaptic transmission in the brain.
In in vitro studies, the perampanel did not compete with AMPA for binding to the AMPA receptor, but it was displaced from binding by non-competitive AMPA receptor antagonists. This indicates that the nephrampanel is a non-competitive AMPA receptor antagonist.
In in vitro studies, the pherampane inhibited AMPA-induced (but not N-methyl-D-aspartate (NMDA) induced) increase in intracellular calcium concentration. In vivo, the penrampanel significantly increased the latent period in the AMPA-induced model of epileptic seizure.
The exact mechanism of the development of the anticonvulsant effect of perampanel in man is subject to further study
Pharmacodynamic effects
Based on the summary of the three efficacy studies conducted with partial epileptic seizures, an analysis was made of the pharmacokinetics and pharmacodynamics of the penrampanel. An analysis was also made of the pharmacokinetics and pharmacodynamics of the penrampanel based on efficacy studies for primary generalized tonic-clonic seizures. According to the results of two analyzes, the magnitude of the effect of the coronary gland correlated with the severity of the decrease in the frequency of seizures.
Impact on psychomotor functions. At doses of 8 and 12 mg, perampanel in single and multiple admission dose-dependent worsened psychomotor functions in healthy volunteers. The effect of the panel on complex psychomotor functions, such as driving, was enhanced by the intake of alcohol. Characteristics of psychomotor functions returned to the baseline values ​​within 2 weeks after discontinuation of the peripanel administration.
Impact on cognitive function. When assessing a series of standard tests of the impact of the impact on memory and memory in healthy volunteers, there was no effect, either with single or repeated administration of the drug at doses up to 12 mg / day.
Influence on mood and speed of reaction to external influence. The rate of response to external influences (excitability) in healthy volunteers who received perampanel in doses from 4 mg to 12 mg per day, decreased dose-dependently. Deterioration of mood in volunteers was noted only on the background of taking 12 mg per day, mood changes were insignificant and reflected a general decrease in the reaction rate to external influences.
Multiple reception of the penrampanel in a daily dose of 12 mg increased the worsening effect of alcohol on vigilance and the response rate to external influences and increased the intensity of irritation, confusion, and depression from the 5-point rating of the Emotional State Profile.
Effect on the electrophysiological parameters of the heart
Perampanel in daily doses up to 12 mg did not extend the QTc interval and did not exert any dose-dependent or clinically significant effect on the duration of QRS complexes.
Clinical efficacy and safety
Partial epileptic seizures
The effectiveness of the Ficompa В® preparation in partial seizures was established during three 19-week, randomized, double-blind, placebo-controlled multicenter trials in adults and adolescents with partial seizures, with or without secondary generalization adequately not controlled by others (one to a combination of the three) antiepileptic drugs (PEP). During the 6-week baseline period, patients were required to have more than 5 seizures, a period without seizures, should not exceed 25 days. In three of these studies, patients had an average duration of the disease of 21.06 years. From 85.3 to 89.1% of patients took 2 or 3 PEP with or without concomitant vagus nerve stimulation.
In the first two studies, the preparation Ficompa В® in daily doses of 8 and 12 mg, and in the third - in daily doses of 2, 4 and 8 mg was compared with placebo.
In all three studies, after a 6-week baseline period prior to randomization and required to establish a baseline frequency of epileptic seizures, patients were randomized and received titrated to randomized dose values. During the titration period, in all three studies, treatment started with a dose
2 mg / day, which was increased weekly by 2 mg / day until the target dose was reached. Patients with intolerable side effects could remain at the same dose or their dose was reduced to a previously well tolerated dose. In all three studies, the period of titration was followed by a maintenance period that lasted 13 weeks and during which patients were to receive a constant dose of Ficompa В® .
According to the combined results of the three studies, the proportion of 50% of the response was 19% for the placebo group, 29% for the 4 mg dose, 35% for the 8 mg and 35% for the 12 mg dose. A statistically significant reduction in the frequency of seizures in 28 days compared with placebo was shown for dosages of 4 to 12 mg per day for a single dose.
These results show that the administration of perampanel in doses of 4 to 12 mg once a day as an additional therapy in this group of patients is significantly more effective than in placebo.
Clinically significant improvement in control over seizures was observed with a single admission of 4 mg of Ficompa В® in a day, and increased with an increase in the daily dose to 8 mg. With an increase in the daily dose to 12 mg not
There was an additional increase in the effectiveness of the drug compared with a dose of 8 mg for the entire population of patients. An increase in the effectiveness of the preparation Fikcom В® in a dose of 12 mg was noted only in patients resistant to a dose of 8 mg.
A clinically significant reduction in the frequency of seizures with placebo was achieved as early as the second week after reaching a daily dose of 4 mg.
97% (1186) of the patients who completed the randomized trials were included in the open-label extended study in which they took a no less than 1 year perampanel at an average daily dose of 10.05 mg.
In these three basic double-blind, placebo-controlled studies, Phase 3 involved 143 adolescents aged 12 to 18 years. The results obtained in adolescents were similar to the results of adult patients.
Primary-generalized tonic-clonic seizures
The effectiveness of the preparation Fikcom В® as an additional therapy of primary generalized tonic-clonic seizures in 164 patients aged 12 years and older with idiopathic generalized epilepsy was established in a multicenter, randomized, double-blind, placebo-controlled study. The study included patients who took stable doses of 1 to 3 PEP and had at least 3 primary-generalized tonic-clonic seizures throughout the 8-week baseline period. Selection of the dose to the target value of 8 mg / day or to the highest tolerated dose was carried out for 4 weeks. The maintenance period was 13 weeks at the level of the last dose reached at the end of the titration period. The total treatment period was 17 weeks. The test drug was taken 1 time / day.
The proportion of the 50% response in the primary generalized tonic-clonic seizures was 64.2% in the group of perampanel and 39.5% in the placebo group. The median decrease in the frequency of primary generalized tonic-clonic seizures for 28 days was 76.47% in the group of the penrampanel and 38.38% in the placebo group. The estimated difference in treatment efficacy in the perampanel and placebo groups was 30.81%, indicating a significant improvement in the reduction in the incidence of primary generalized tonic-clonic seizures in the perampanel group compared with the placebo group.
Open extended study. Of the 140 patients who completed the baseline study, 114 (81.4%) within 6 weeks were transferred to a daily dose of 4-8 mg (73.7% of patients) or more than 8-12 mg (16.7% of patients) for a period of at least 1 year.
The study involved 22 teenagers aged 12 to 18 years. The results obtained in adolescents were similar to those obtained in the adult population.
PHARMACOKINETICS
The pharmacokinetics of perampanel were studied in healthy volunteers aged 18 to 79 years, in adults and adolescents with partial epileptic seizures and primary generalized tonic-clonic seizures, in adults with Parkinson's disease, diabetic nephropathy and multiple sclerosis, as well as in patients with hepatic impairment .
Suction
When taken internally, the panampanel is quickly and completely absorbed, the effect of "first passage" through the liver is negligible. Eating does not affect the degree of absorption, but slows its speed. Compared to fasting with simultaneous reception of the drug with food, the maximum concentration of the plasma in the plasma is reduced, and the time of its achievement is increased by 2 h.
Distribution
In vitro studies indicate that the membrane is approximately 95% bound to plasma proteins. In vitro, it has been shown that the piperpanel is neither a substrate nor a significant inhibitor of the transport anion of organic anions (OATP) 1B1 and 1B3, carriers of organic anions (OAT) 1, 2, 3 and 4, carriers of organic cations (OCT) 1, 2 and 3, as well as P-glycoprotein and breast cancer resistance protein (BCRP).
Metabolism
Perampanel is largely metabolized by primary oxidation and subsequent glucuronation.
According to the results of in vitro studies with recombinant cytochrome P450 in human liver microsomes, the primary oxidative metabolism is mediated by CYP3A isoenzymes. However, the metabolism of the penrampanel has not yet been fully understood, and its other pathways can not be ruled out.
After the application of a radio-labeled perampanel, only trace amounts of its metabolites are detected in the plasma.
Excretion
After receiving the radioactively labeled perampanel by eight healthy elderly volunteers, 30% of the radioactive label was detected in urine and 70% in feces. The radioactive label isolated was mainly a mixture of oxidized and conjugated metabolites. In a population pharmacokinetic analysis of the summary data of 19 clinical studies of the 1 phase, the mean T 1/2 of the spanpan was 105 hours. When used simultaneously with carbamazepine, which is a potent inducer of the CYP3A isoenzyme, the mean T 1/2 of the peripanel was 25 h.
Linearity / nonlinearity
In healthy volunteers, the concentration of the penrampanel in the plasma increases in direct proportion to the dose in the range of 2 to 12 mg. In a population pharmacokinetic analysis in patients with partial seizures receiving perampanel at doses up to 12 mg per day and in patients with primary generalized tonic-clonic seizures who received perampanel in doses up to 8 mg / day in placebo-controlled clinical trials, between the magnitude dose and concentration of the penampanel in the plasma, a linear relationship was established.
Use in special patient groups
Patients with hepatic insufficiency. The pharmacokinetics of the penrampanel after a single dose of 1 mg was evaluated in 12 patients with mild to moderate hepatic insufficiency (classes A and B on the Child-Pugh scale) and demographically corresponding to them 12 healthy volunteers. The average apparent clearance of an unbound band in mild liver failure was 188 ml / min vs 338 ml / min in healthy volunteers and 120 ml / min (vs. 392 ml / min) at moderate levels. T 1/2 in patients with hepatic insufficiency was prolonged: at mild degree - up to 306 h against 125 h in healthy volunteers, at moderate degree - up to 295 h against 139 h.
Patients with renal insufficiency. The pharmacokinetics of perampanel in patients with renal insufficiency have not been studied separately. Elimination of the perampanel is carried out almost exclusively by the formation of metabolites followed by their rapid excretion. In the plasma, only trace amounts of metabolites of the penampanel are detected. In a population pharmacokinetic analysis in patients with partial seizures and creatinine clearance of 39-160 ml / min, who received in the course of placebo-controlled studies of perampanel in doses up to 12 mg per day, there was no relationship between the clearance of the penampanel and QC. In a population pharmacokinetic analysis, patients with primary generalized tonic-clonic seizures who received perampanel at doses up to 8 mg / day during placebo-controlled studies did not observe a relationship between the clearance of the peanpanel and the initial QC.
Influence of sex. In a population pharmacokinetic analysis in patients with partial seizures who received in the course of placebo-controlled studies of perampanel in doses up to 12 mg per day and in patients with primary generalized tonic-clonic seizures who received perampanel at doses up to 8 mg / day, the clearance of the penrampanel in women (0.54 l / h) was 18% lower than in men (0.66 l / h).
Patients of advanced age (? 65 years). In a population pharmacokinetic analysis in patients aged 12 to 74 years with partial seizures that received in the course of placebo-controlled studies of perampane in doses up to 12 mg per day and in patients with primary generalized tonic-clonic seizures receiving perampanel in doses up to 8 mg / day, there was no significant effect of age on the clearance of the penrampanel.
Patients of childhood. In population pharmacokinetic analysis, no significant differences from the general population were found in adolescent patients who participated in clinical trials of the 3 phase.
Drug interaction studies
Evaluation of drug interactions in vitro
inhibition of enzymes involved in the metabolism of drugs. In human liver microsomes perampanel (at a concentration of 30 pmol / l) exerted a weak inhibitory effect on CYP2C8, and UGT1A9 among other hepatic enzyme and UDP-glyukuronilransferaz (UGT).
The induction of enzymes involved in the metabolism of drugs . In comparison with control drugs (including phenobarbital and rifampin), perampanel has little effect on inducing CYP2B6 (at a concentration of 30 pmol / l) CYP 3 A 4/5 (at a concentration of at least 3 mol / l) among major liver enzymes and in UGT cultured human hepatocytes.
INDICATIONS
- as part of an adjunctive therapy in the treatment of partial seizures in patients with epilepsy aged 12 years and older with or without secondarily generalized seizures;
- as part of an adjunctive therapy for the treatment of primary generalized tonic-clonic seizures in patients with epilepsy aged 12 years and older.
DOSING MODE
Use in adults and adolescents
Perampanel taken orally 1 time a day at bedtime independently of food intake. Tablets should be swallowed whole , washed down with a glass of water 1. Tablet can not chew, crush or crumble, because the tablet can not be neatly divided, since there are no risks.
Partial seizures
has been shown that the drug Faykompa В® at daily dosages of from 4 to 12 mg is effective in the treatment of partial seizures. Receiving Faykompa preparationВ®should begin with a dose of 2 mg / day. The dose may be increased according to clinical response and tolerability in increments of 2 mg (once a week or once every two weeks) to 4-8 mg / day. Depending on individual clinical response, and tolerability of the drug in a dose of 8 mg per day, may further increase the drug dose Faykompa В® to 12 mg / day in increments of 2 mg not more than once a week. In patients concomitantly receiving AEDs, not decreasing half-life perampanela, perampanela dose titration should take place at two-week intervals. In patients concomitantly receiving AEDs that reduce the half-life perampanela should be titrated (increased) dose perampanela once a week (see. "Drug interactions".
Primary generalized tonic-clonic seizures
was shown that the preparation Faykompa В®at daily doses up to 8 mg is effective in the treatment of primary generalized tonic-clonic seizures. Some patients may show a higher dose (12 mg / day). The drug should be started with a dose of 2 mg / day. The dose may be increased according to clinical response and tolerability in increments of 2 mg (once a week or once every two weeks with the half-life of the drug) to 8 mg / day. Depending on individual clinical response, and tolerability of the drug in a dose of 8 mg / day, may further increase the dose to 12 mg / day. In patients concurrently treated with AEDs, not decreasing half-life perampanela. Perampanela dose titration should take place at two-week intervals. In patients concomitantly receiving AEDs that reduce the half-life perampanela,should be titrated (increased) dose perampanela once a week.
Despite the fact that perampanel has a long half-life, it is recommended, as for other probes, to abolish it gradually to minimize the potential for increasing the frequency of attacks.
A single pass of the drug: in view of the fact that perampanel has a sufficiently long half-life, the patient should wait and take the next scheduled dose in accordance with an agreed scheme of treatment.
In case more than one missed reception dose(total duration of no less than 5 drug half-lives of 3 weeks for patients not receiving AEDs, altering metabolism perampanela and 1 week for patients receiving AEDs, altering metabolism perampanela), should consider the resumption of the drug in the last dose received.
If the patient is taking the drug was interrupted for a period of more than 5 half-lives, it is necessary to follow the recommendations of both the initiation of therapy.
Use in children under 12 years of
safety and efficacy perampanela in children under 12 years has not been established (see. "Contraindications").
Use in elderly patients (over 65 years)
in the clinical trials of the drug Faykompa В®participated insufficient number of patients with epilepsy aged 65 years to assess the differences with younger patients. Safety analysis of information for patients taking perampanel did not reveal differences in the safety profile based on age. These data suggest that dose adjustment perampanela based on age is not required. In elderly patients perampanel should be used with caution (see. "Drug Interactions", "Special Instructions").
The use in patients with renal insufficiency
In renal insufficiency mild perampanela dose adjustment is required. Application Faykompa preparation В®in patients with moderate to severe renal impairment or in patients undergoing hemodialysis is not recommended (see. "Contraindications").
The use in patients with hepatic insufficiency
dose Increase in patients with liver failure mild and moderate, and as the other patients, is made depending on the clinical response and tolerability. Since liver failure mild and moderate half-life perampanela lengthened, the minimum time interval before each dose escalation should be two weeks, and the maximum dose - does not exceed 8 mg daily. The use is not recommended (see. "Contraindications") with severe hepatic insufficiency.
SIDE EFFECT
Among 1639 patients with partial seizures receiving perampanel in all of clinical trials, 1147 were treated for 6 months and 703 - more than 12 months.
In controlled and uncontrolled trials in patients with primary generalized tonic-clonic seizures in 68 patients taking perampanel for 6 months, and 36 patients - for more than 12 months.
Partial seizures
Adverse reactions, leading to the exit of patients with partial seizures of controlled studies 3 phases, observed in the 1.7, 4.2 and 13.7% in patients treated perampanel, respectively, at doses of 4, 8 and 12 mg per day, and 1.4% - in patients treated with placebo. Most often, the studies yield factors were dizziness and somnolence.
Primary generalized tonic-clonic seizures
in controlled clinical trials phase 3 in patients with primary generalized tonic-clonic seizures adverse reactions that led to the exit of patients from the study were reported in 4.9% of patients in the group perampanela and 1.2% in the placebo group. Adverse reactions, most often leads to the exit from the study were dizziness.
Listed below are adverse events (AEs) are indicated in the application perampanela, according to the system-organ class and their frequency of occurrence. To evaluate the incidence of adverse events following classification is used: very common (1/10?); often (? 1/100, <1/10).
Violations by the Metabolism and nutrition:often - decreased appetite, increased appetite.
Mental disorders: often - aggression, anger, anxiety, confusion.
Disorders of the nervous system: very often - dizziness, drowsiness; often - ataxia, dysarthria, impaired balance, irritability.
Violations by the organ of vision: often - diplopia, blurred vision.
Violations by the organ of hearing and labyrinth disorders: often - central vertigo.
Violations of the gastrointestinal tract: often - nausea.
Violations by the musculoskeletal system and connective tissue disorders: often - pain in the back.
General disorders: often - gait disturbance, fatigue.
Laboratory and instrumental data: often - increased body mass.
Injury, poisoning and complications of manipulation: often - fall.
Teens
Based on data from clinical studies involving 165 adolescents can be expected that the frequency, nature and severity of adverse reactions they are the same as in adults.
Notification of adverse reactions
is extremely important to notify about adverse reactions that occurred during post-marketing use of the drug. This allows you to control the ratio of benefits and risks in its application. Please inform health professionals about the occurrence of any adverse reactions to the address indicated in this manual.
CONTRAINDICATIONS
- perampanelu or hypersensitivity to any of the excipients of the formulation;
- pregnancy
- lactation period;
- severe renal insufficiency; patients on hemodialysis;
severe hepatic impairment;
- Children under 12 years of age (efficacy and safety data are not available);
- galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
PREGNANCY AND LACTATION
Women with genital stored potential and contraception
woman with a stored childbearing potential not using contraception, drug reception Faykompa В® recommended only when absolutely necessary.
Pregnancy
Usage data perampanela pregnant significantly limited (less than 300 cases). Studies in animals did not reveal any teratogenic effect, but have shown embryotoxicity at doses toxic to the mother's body. As a precaution, it is recommended to avoid the use of the drug Faykompa В® during pregnancy.
Breastfeeding period
In animal studies it has been shown that perampanel and / or its metabolites are excreted in breast milk. It is not known whether perampanel is allocated to breast milk in humans, so the risk to the child can not be excluded.
Given the advantages of breastfeeding for the child and care for a woman, you must either stop breast-feeding or to abstain from taking / stop taking the drug Faykompa В® during breastfeeding.
The effect on fertility
in animal studies have shown that high doses (30 mg / kg) and extends perampanel gives regularity of the estrous cycle, but these changes did not affect fertility and early fetal development. Effects on male fertility were found. Perampanela effect on human fertility has not been studied.
APPLICATION FOR FUNCTIONS OF THE LIVER
In renal insufficiency, mild dose adjustment perampanela not required. Application Faikompa drug in patients with moderate to severe renal impairment or in patients undergoing hemodialysis is not recommended.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Increasing doses in patients with liver failure mild and moderate, and as the other patients, is made depending on the clinical response and tolerability. Since liver failure mild and moderate half-life perampanela lengthened, the minimum time interval before each dose escalation should be two weeks, and the maximum dose - does not exceed 8 mg daily. Use in severe hepatic impairment is not recommended.
APPLICATION FOR CHILDREN
The safety and efficacy perampanela in children under 12 years has not been established
APPLICATION IN ELDERLY PATIENTS
In clinical studies, the drug involved Faykompa insufficient number of patients with epilepsy aged 65 years to assess the differences with younger patients. Safety analysis of information for patients taking perampanel did not reveal differences in the safety profile based on age. These data suggest that dose adjustment perampanela based on age is not required. In elderly patients perampanel should be used with caution
SPECIAL INSTRUCTIONS
Suicide alertness
in patients taking AEDs for various indications, there have been cases of suicidal thinking and behavior. A meta-analysis of randomized placebo-controlled trials of AEDs has also shown a small increased risk of suicidal thinking and behavior. The mechanism of increased risk is unknown at present we can not exclude the likelihood of this risk and improve the application of the preparation Faykompa В® . Consequently, patients should be monitored in order to detect symptoms of suicidal behavior and thinking; It must be assigned to the appropriate treatment. Patients or caregivers for them, should be made aware of the need to seek medical care for symptoms of suicidal thinking or behavior.
Disorders of the nervous system
Perampanel can cause dizziness and drowsiness, and thereby affect the ability to drive vehicles and use machinery.
Oral contraceptives
Against reception Faykompa preparation В® in a dose of 12 mg / day efficacy progestin-containing hormonal contraceptives can be reduced (see. The section "Patient interaction"). In these cases it is necessary to provide for the use of additional non-hormonal contraceptive methods.
Completion of therapy
recommended to complete therapy with Faykompa В®gradually in order to minimize the possibility of increasing the frequency of seizures (see. section "Dosage"). In extreme cases there may be an abrupt cessation of the drug, taking into consideration its long period of breeding and the relatively slow decline in plasma concentration after stopping.
Fall
The tendency to increase the number of falls, particularly in elderly patients, the cause of which is unknown.
Aggression
Cases of aggressive and hostile behavior in patients receiving therapy perampanelom. In clinical studies perampanela aggression, anger and irritability occurred more frequently when applied in higher doses. The majority of these adverse events were mild or moderate and were both independently and at lower doses. However, thoughts of hurting others, physical assault or threatening behavior have been observed in some patients (<1% in clinical trials perampanela). Patients and carers for them, should be advised to report immediately to your doctor if significant changes in mood or behavior. perampanela dose should be reduced, with the appearance of symptoms and treatment should be discontinued immediately if symptoms are severe.
The development of dependence
must be taken when administering the drug Faykompa В® patients with a history of drug dependence cases. Such patients should be observed for the timely identification of the possible dependence to perampanelu.
Concomitant therapy AEDs that induce CYP3A
Partial seizures. The efficiency of fixed-dose perampanela
