Файкомпа™

General characteristics. Structure:

Active ingredient: 2 mg, 4 mg, 6 mg, 8 mg or 10 mg of a perampanel.

Excipients: lactoses monohydrate, the hypro rod low-replaced, povidone, magnesium stearate.

Cover of 2 mg: опадрай orange (gipromelloza of 2910 56,0%, talc of 28,0%, macrogoal-8000 of 10,0%, titanium dioxide of 4,0%, dye ferrous oxide of yellow 1,8%, dye ferrous oxide of red 0,2%).

Cover of 4 mg: опадрай red (gipromelloza of 2910 56,0%, talc of 28,0%, macrogoal-8000 of 10,0%, titanium dioxide of 4,0%, dye ferrous oxide of red 2,0%).

Cover of 6 mg: опадрай pink (gipromelloza of 2910 56,0%, talc of 25,0%, macrogoal-8000 of 10,0%, titanium dioxide of 8,6%, dye ferrous oxide of red 0,4%).

Cover of 8 mg: опадрай purple (gipromelloza of 2910 56,0%, talc of 29,4%, macrogoal-8000 of 10,0%, titanium dioxide of 4,0%, dye ferrous oxide of red 0,4%, dye ferrous oxide of black 0,2%).

Cover of 10 mg: опадрай green (gipromelloza of 2910 50,9%, talc of 24,0%, macrogoal-8000 of 9,1%, titanium dioxide of 8,0%, dye ferrous oxide of yellow 1,5%, indigo carmine of 6,5%).

Cover of 12 mg: опадрай blue (gipromelloza of 2910 50,9%, talc of 25,5%, macrogoal-8000 of 9,1%, titanium dioxide of 8,0%, indigo carmine of 6,5%).

Pharmacological properties:

Pharmacodynamics. Action mechanism. Perampanel is the first in the class selection non-competitive antagonist ionotropny -амино-3-гидрокси-5-метил-4-изоксазолпропионат - (AMPA) of glutamate receptors on postsynaptic neurons.

Glutamate - the main exciting neurotransmitter in the central nervous system (CNS) playing an important role in a pathogeny of a number of the neurologic diseases caused by overexcitation of neurons.

It is supposed that activation of AMPA receptors a glutamate is responsible for the most bystry exciting synoptic transfer in a brain. In the researches in vitro perampanet inhibited the AMPA induced increase in intracellular concentration of calcium. The exact mechanism of development of anticonvulsant effect of a perampanel in the person is subject to further studying.

Pharmakodinamichesky effects. On the basis of aggregated data of three conducted efficiency researches at partial epileptic attacks the analysis of pharmacokinetics and a pharmacodynamics of a perampanel was carried out. The size of influence of a perampanel correlated with expressiveness of decrease in frequency of attacks.

Impact on psychomotor functions. When studying effect of a perampanel at healthy volunteers in a series of the standard tests including driving simulation perampanet did not break performance of simple psychomotor tasks and did not influence characteristics of driving, and also sensory-motor coordination both at single, and at fractional reception of a daily dose of 4 mg.

In doses of 8 and 12 mg perampanet at single and multiple dose дозозависимо worsened psychomotor functions. At reception of a dose of 12 mg ability to drive the car worsened, but stability of position of a body in space significantly did not worsen. Characteristics of psychomotor functions were returned to reference values within 2 weeks after the termination of reception of a perampanel. In the same research at appointment to the healthy volunteers accepting alcohol before achievement of its concentration in blood of 80-100 mg / 100 ml perampanet steadily worsened simple psychomotor functions, as at a single dose in a dose from 4 to 12 mg, and at multiple dose in a dose of 12 mg a day within 21 days. The effect rendered perampanely on difficult psychomotor functions, such as driving amplified alcohol intake.

Impact on cognitive function. At assessment in a series of standard tests of impact of a perampanel on speed of response on external influence and memory at healthy volunteers of any influence both at single, and at multiple dose of drug in doses to 12 mg a day it was not noted.

Influence on mood and speed of response on external influence. Perampanet speed of response on external influence (excitement) at the healthy volunteers receiving in doses from 4 mg to 12 mg a day, дозозависимо decreased. Deterioration in mood at volunteers was noted only against the background of reception of 12 mg a day, changes of mood were insignificant and reflected the general reduction in the rate of reaction to external influence.

At fractional reception of a daily dose of 12 mg perampanet strengthened the worsening effect of alcohol on attentiveness and speed of response on external influence and increased expressiveness of annoyance, confusion of consciousness and a depression.

Influence on electrophysiologic hearts of parameter. During double-blind, randomized, placebo - and moxifloxacin - a controlled research was estimated influence of a perampanel on an ECG of healthy volunteers. Perampanel appointed in a dose up to 12 mg a day within 7 days. Drug did not extend an interval of QTc and did not make any dozozavisimy or clinically significant impact on duration of the QRS complexes.

Clinical performance and safety. Efficiency of drug Faykompa at partial attacks was established during three 19 weeks randomized double-blind placebos - controlled multicenter researches at adults and teenagers with partial attacks at the existence or lack of secondary generalization which adequately are not controlled by others (from one to a combination from three) antiepileptic drugs (PEP). In the early two studies Faykomp's drug in daily doses of 8 and 12 mg, and in the third - in daily doses of 2, 4 and 8 mg was compared to placebo.

In each of these basic researches III of a phase clinical advantage of a perampanel at use as additional therapy of partial attacks with existence or lack of secondary generalization at adults and children was established, since 12 years.

Primary criterion of efficiency in each of three researches was decrease in frequency of attacks in comparison with placebo in 28 days. Clinically significant improvement of control over attacks, irrespective of the accompanying therapy, was observed at a single dose of 4 mg of drug of Faykomp in days, and increased at increase in a daily dose to 8 mg. At increase in a daily dose up to 12 mg additional increase in efficiency of drug in comparison with a dose of 8 mg concerning all population of patients was not observed. Increase in efficiency of drug of Faykomp in a dose of 12 mg was noted only at patients, resistant to a dose of 8 mg.

Clinically significant decrease in frequency of attacks concerning placebo was reached on the second week after achievement of a daily dose of 4 mg. These results show that reception of a perampanel in doses from 4 to 12 mg of 1 times a day as additional therapy in this group of patients is much more effective in comparison with placebo.

Teenagers aged from 12 up to 18 years took part in these three basic double blind placebos - controlled researches III of a phase. The results received at teenagers were similar to results of adult patients.

Pharmacokinetics. The pharmacokinetics of a perampanel was studied at healthy volunteers aged from 18 up to 79 years, at adults and teenagers with partial epileptic attacks, at adults with Parkinson's disease, a diabetic nephropathy and multiple sclerosis, and also at patients with a liver failure.

Absorption. At intake perampanet quickly and it is completely soaked up, the effect of "the first passing" through a liver is insignificant. Meal does not influence extent of absorption, but slows down its speed. In comparison with reception on an empty stomach at a concomitant use of drug with food, the maximum concentration of a perampanel in plasma decreases, and time of its achievement increases by 2 h.

Proportionality of a dose. At healthy volunteers concentration of a perampanel in plasma increases in direct ratio to a dose in the range from 2 to 12 mg. In the population pharmacokinetic analysis at the patients with partial attacks receiving perampanet in doses up to 12 mg a day in placebo - controlled clinical trials, between the size of a dose and concentration of a perampanel in plasma linear dependence was established.

Distribution. Data of the researches in vitro indicate what perampanet approximately for 95% contacts proteins of plasma. in vitro was shown that perampanet is not either substrate, or significant inhibitor of transport peptides 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, and also the R-glycoprotein and protein of resistance of a breast cancer (BCRP).

Metabolism. Perampanel is substantially metabolized by primary oxidation and the subsequent glyukuronirovaniye. According to results of the researches in vitro with recombinant P450 cytochrome in microsomes of a liver of the person primary oxidizing metabolism is mediated by isoenzymes of CYP3A4 and/or 3A5.

After use it is radioactive a marked perampanel in plasma only trace quantities of its metabolites are defined.

Removal. After reception it is radioactive a marked perampanel healthy elderly volunteers, 30% of a radioactive label found in urine and 70% - in Calais. The allocated radioactive label, represented, mainly, mix of the oxidized and conjugated metabolites. In the population pharmacokinetic analysis of aggregated data of 19 clinical trials of the I phase, the average elimination half-life (T½) of a perampanel made 105 h. At simultaneous use with the carbamazepine which is the powerful inductor of an isoenzyme CYP3A4, T½ of a perampanel made 25 h.

Use in special groups of patients. Patients with a liver failure. Pharmacokinetics of a perampanel after reception of a single dose of 1 mg estimated at patients with a liver failure of easy and moderate degree (classes A and B on a scale of Chaylda-Pyyu) and demographically the healthy volunteers corresponding to them. The average seeming clearance of an untied perampanel at a liver failure of easy degree made 188 ml/min. against 338 ml/min. at healthy volunteers, and 120 ml/min. (against 392 ml/min.) - at moderate degree. Т½ at patients with a liver failure it was extended: at easy degree - to 306 h against 125 h at healthy volunteers, at moderate degree - to 295 h against 139 h.

Patients with a renal failure. The pharmacokinetics of a perampanel at patients with a renal failure was separately not studied. Elimination of a perampanel is carried out almost only by formation of metabolites with the subsequent their bystry excretion. In plasma find only trace quantities of metabolites of a perampanel. In the population pharmacokinetic analysis at patients with partial attacks and clearance of creatinine of 39-160 ml/min. receiving during placebo - controlled researches perampanet in doses up to 12 mg a day, dependence between clearance of a perampanel and clearance of creatinine was not noted.

Influence of a floor. In the population pharmacokinetic analysis at the patients with partial attacks receiving during placebo - controlled researches perampanet in doses up to 12 mg a day, the clearance of a perampanel at women (0,605 l/h) was 17% lower, than at men (0,730 l/h).

Patients of advanced age (≥65 years). In the population pharmacokinetic analysis at patients aged from 12 up to 74 years with partial attacks receiving during placebo - controlled researches perampanet in doses up to 12 mg a day, the significant influence of age on clearance of a perampanel was not revealed.

Patients of children's age. In the population pharmacokinetic analysis at the patients of teenage age participating in clinical trials of the III phase noticeable differences from the general population were not revealed.

Indications to use:

Faykomp's drug is shown as supportive application for treatment of partial attacks at patients with epilepsy aged from 12 years and is more senior at existence or lack of secondary and generalized attacks.

Route of administration and doses:

Use for adults and teenagers. Perampanel accept inside once a day before going to bed it is not dependent on meal. The tablet needs to be swallowed entirely, washing down with 1 glass of water. The tablet cannot be chewed, crumbled or broken because the tablet cannot be accurately divided as on it there are no risks.

It was shown that Faykomp's drug in daily doses from 4 to 12 mg is effective at treatment of partial epileptic attacks. Administration of drug of Faykomp it is necessary to begin with a dose 2 mg a day. The dose can be increased depending on the clinical answer and portability with a step of 2 mg not more often than once a week to 4-8 mg a day. Depending on the individual clinical answer and portability of drug in a dose of 8 mg a day, perhaps further increase in a dose of drug of Faykomp to 12 mg a day with a step of 2 mg not more often than once a week. In spite of the fact that perampanet possesses a long elimination half-life, it is recommended, as well as for other PEP, to cancel it gradually to minimize probability of increase in frequency of attacks.

Single admission of administration of drug: because perampanet has rather long elimination half-life, the patient has to wait and accept the following planned dose according to the coordinated scheme of administration of drug.

If reception more than 1 dose is missed (the general duration without drug of less than 5 elimination half-lives: 3 weeks for the patients who are not receiving PEP, changing metabolism of a perampanel and 1 week for patients, the receiving PEP changing metabolism of a perampanel), it is necessary to consider a question of resuming of administration of drug in the last accepted dose.

If the patient interrupted administration of drug for the term of more than 5 elimination half-lives, it is necessary to follow recommendations as at treatment initiation.

Use for children is younger than 12 years. Safety and efficiency of a perampanel at children are younger than 12 years is not established (see the section "Contraindications").

Use for patients of advanced age (65 years are more senior). The insufficient number of patients with epilepsy participated in clinical trials of drug of Faykomp 65 years for assessment of distinctions with younger patients are more senior. The analysis of information on safety at the patients accepting perampanet, did not reveal distinctions in a safety profile depending on age. These data confirm that dose adjustment of a perampanel depending on age is not required. At elderly patients perampanet it is necessary to apply with care (see. "Interaction with other medicines", "Special instructions").

Use for patients with a renal failure. At a renal failure of easy degree dose adjustment of a perampanel is not required. Use of drug of Faykomp for patients with a medium-weight and heavy renal failure or the patients who are on a hemodialysis is not recommended (see the section "Contraindications").

Use for patients with a liver failure. Increase in a dose at patients with a liver failure of easy and average degree, as well as at other patients, is made depending on the clinical answer and portability. As at a liver failure of easy and average degree the elimination half-life of a perampanel is extended, the minimum time interval before each increase in a dose has to make two weeks, and the maximum dose - not to exceed 8 mg a day. Use at a heavy liver failure is not recommended (see the section "Contraindications").

Features of use:

Use at pregnancy and during breastfeeding. Pregnancy. Data on use of a perampanel for pregnant women are significantly limited (less than 300 cases). In researches of reproductive toxicity at animal straight lines or indirect toxic effects it is not revealed. As a precautionary measure it is recommended to avoid use of drug of Faykomp at pregnancy.

Breastfeeding period. In researches on animals it was shown that perampanet and/or its metabolites are allocated with breast milk. It is unknown whether it is allocated perampanet with breast milk at the person therefore the risk for the child cannot be excluded. Considering advantage both breastfeeding to the child, and therapy for the woman, it is necessary either to stop breastfeeding, or to refrain from reception / to stop administration of drug of Faykomp during breastfeeding.

Suicide vigilance. At the patients accepting PEP according to various indications cases of suicide thinking and behavior were noted. Meta-analysis of randomized placebos - controlled researches PEP also showed small increase in risk of suicide thinking and behavior. The mechanism of increase in risk is unknown, now it is impossible to exclude probability of increase in this risk and at use of drug of Faykomp. Thereof, patients have to be under observation for the purpose of identification of symptoms of suicide thinking and behavior; the corresponding treatment has to be appointed. The patients or persons who are carrying out care of them have to be informed on need of the request for medical care at emergence of signs of suicide thinking or behavior.

Contraception. Patients with safe genital function during reception of a perampanel and, at least, within 1 month after its termination, have to apply adequate methods of contraception. Against the background of administration of drug of Faykomp in a dose of 12 mg / дн efficiency of the hormonal contraceptives containing levonorgestrel can be reduced owing to probability of medicinal interaction (see the section "Interaction with Other Medicines"). It is necessary to provide use of additional non-hormonal methods of contraception in these cases.

Completion of therapy. It is recommended to complete therapy by Faykomp's drug gradually to minimize probability of increase in frequency of attacks. In extreme cases perhaps sharp termination of administration of drug, considering its long period of removal and rather slow decrease in its concentration in plasma after the reception termination.

Falling. The tendency which reason is not known, to increase in number of falling, especially, at elderly patients is noted.

Aggression. Aggression cases are registered, and their frequency was higher at the patients accepting higher doses of drug of Faykomp. The majority of these undesirable phenomena were easy or moderately severe and passed as independently, and at a dose decline. In hard cases of an agressive behavior treatment had to be stopped. Thus, it is necessary to follow strictly the rule of titration of a dose and to resort to its decrease at preservation at the patient of symptoms of aggression.

Dependence development. It is necessary to be careful at purpose of drug of Faykomp to the patients having cases of development of medicinal dependence in the anamnesis. Such patients need to be observed for early detection of development of possible dependence to a perampanel.

The accompanying therapy of PEP (CYP 3A inductors). In the fixed doses those patients who received the accompanying antiepileptic therapy of CYP 3A inductors (carbamazepine, Phenytoinum, окскарбазепин), than at the patients receiving fermental and inactive PEP had an efficiency of a perampanel less. 50% the share answered treatment perampanely in a dose of 4 mg, made 8 mg and 12 mg, respectively, 23%, 31,5% and 30% against the background of reception of PEP CYP 3A of inductors, and, respectively, 33,3%, those patients who accepted fermental and inactive PEP have 46,5% and 50,0%. The effect of therapy perampanely has to monitorirovatsya carefully during the replacing or addition of the accompanying PEP. Depending on the individual clinical response to treatment and portability of drug, the dose can be increased or reduced with a step of 2 mg.

Influence on ability of control of vehicles and works with mechanisms. Faykompa possesses moderate impact on ability to manage vehicles and to work with mechanisms. Perampanel can cause dizziness and drowsiness and, thereby, to influence ability of management of transport and uses of mechanisms. Patients are not recommended to manage vehicles, to work with the difficult equipment or to be engaged in other potentially dangerous types of activity until it becomes clear whether influences perampanet on their ability to perform these operations.

Side effects:

Among patients with the partial attacks receiving perampanet in all the conducted clinical trials, 72% accepted drug within 6 months and 43% - more than 12 months.

The undesirable reactions leading to an exit of patients from controlled researches III of a phase were noted in 1,7, 4,2 and 13,7% at the patients receiving perampanet, respectively, in doses 4, 8 and 12 mg a day, and in 1,4% - at the patients receiving placebo. Most often dizziness and drowsiness were the reasons of an exit from researches (≥1% in summary group of a perampanel, than in group of placebo).

The undesirable phenomena (UP) noted at use of a perampanel according to system and organ classes and frequency of their occurrence are listed below. The following classification is applied to assessment of frequency of emergence of the undesirable phenomena: very often (≥1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/100); seldom (≥1/10 000, <1/1000).

Disturbances of food and metabolism: often - a loss of appetite, increase in appetite.

Mental disturbances: often - aggression, anger, concern, confusion of consciousness.

Disturbances from a nervous system: very often - dizziness, drowsiness; often - an ataxy, a dysarthtia, balance disturbance, an acrimony.

Disturbances from an organ of sight: often - a diplopia, a sight illegibility.

Disturbances from acoustic organs and labyrinth disturbances: often - the central dizziness.

Disturbances from digestive tract: often - nausea.

Disturbances from skeletal and muscular system and connecting fabric: often - a dorsodynia.

General disturbances: often - gait disturbance, fatigue.

Laboratory and tool data: often - increase in body weight.

Injuries, intoxications and complications of manipulations: often - falling.

Teenagers. On the basis of these clinical trials it is possible to expect that frequency, character and expressiveness of undesirable reactions at teenagers the same, as at adults.

Interaction with other medicines:

Peroral contraceptive means. In a dose of 12 mg a day perampanet reduced the maximum concentration (Cmax) and the area under a curve "concentration time" (AUC) of levonorgestrel approximately by 40%. The patients accepting Faykomp's drug should consider probability of decrease in efficiency of the contraceptive means containing levonorgestrel and to use additional methods of contraception (intrauterine means or condoms).

Ketokonazol. Healthy volunteers at multiple dose have a ketokonazola, CYP3A4 isoenzyme inhibitor, after a single dose of a perampanel in a dose of 1 mg of T½ of the last AUC0-∞ - for 20% increased by 15%, and.

P450 cytochrome. It is considered that perampanet is not either powerful inhibitor, or the powerful inductor of isoenzymes of P450 cytochrome. In a research of medicinal interaction at healthy volunteers triple increase in clearance of a perampanel at simultaneous use with carbamazepine was shown. In the population pharmacokinetic analysis at patients with the partial attacks receiving in placebo - controlled clinical trials perampanet up to 12 mg in daily doses, the similar result was noted.

The general clearance of a perampanel increases at simultaneous use with carbamazepine (by 3 times), Phenytoinum (twice) and okskarbazepiny (twice) - CYP3A4 isoenzyme inductors. This effect should be considered at addition or cancellation of these PEP in the course of treatment.

Other powerful inductors of isoenzymes of P450 cytochrome, such as rifampicin and St. John's Wort made a hole, are also capable to reduce concentration of a perampanel in plasma. Felbamat can also reduce concentration of a perampanel in plasma.

Effect of a perampanel on at the same time applied PEP. In the population pharmacokinetic analysis at patients with the partial attacks receiving Faykomp's drug in doses to 12 mg a day during placebo - controlled clinical trials, reception of a perampanel slightly influenced clearance of clonazepam, a levetiratsetam, phenobarbital, Phenytoinum, topiramat and zonizamid. Statistically significant influence of a perampanel on clearance of carbamazepine, a klobazam, lamotridzhin and valproic acid was noted, but its size at the highest dose of a perampanel (12 mg a day) did not reach 10%. At a concomitant use of drug of Faykomp with okskarbazepiny, the clearance of the last decreased by 26%.

At healthy volunteers Faykomp's drug lowered AUC midazolam by 13% and did not exert impact on AUC or Cmax of a levodopa.

Use for teenagers. Researches of medicinal interaction were conducted only at adults. In the population pharmacokinetic analysis at the teenagers participating in clinical trials of the III phase noticeable distinctions from the general studied population were not noted.

Contraindications:

Hypersensitivity to a perampanel or any of drug excipients.

Pregnancy and period of a lactation.

Heavy renal or liver failure; the patients who are on a hemodialysis.

Children are younger than 12 years (data on efficiency and safety are absent).

Intolerance of a galactose, insufficiency of lactase or glyukozo-galaktozny malabsorption.

Overdose:

Clinical experience of overdose perampanely at the person is limited. In the report on deliberate overdose which could lead up to 264 mg to receiving a dose at the patient consciousness change, agitation and an agressive behavior was observed; recovery took place without effects.

The specific antidote does not exist. The general maintenance therapy including monitoring of vital indicators and the clinical status of the patient is shown. Considering a long elimination half-life of a perampanel, its effects can have big duration. Because of low renal clearance perampanet holding special procedures, such as an artificial diuresis, a hemodialysis or hemoperfusion, ineffectively.

Storage conditions:

To store at a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity: 4 years (for dosages of 2 and 4 mg) or 2 years (for dosages of 6-8-10-12 mg).

Issue conditions:

According to the recipe

Packaging:

Tablets are film coated, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg. On 7 tablets in a blister strip packaging (blister) from aluminum PVC / foil. On 1 blister (for a dosage of 2 mg) or 4 blisters (for dosages of 4-6-8-10-12 mg) together with the application instruction in a cardboard pack.