Expiration date: 04/2025
Active substance: Perampanel
Release form, composition and packing
Tablets, film-coated red-orange color, round, biconcave, with chasing "E 277" on one side and "4" on the other side.
One tablets contains 2, 4, 6 or 8 mg of perampanel.
Excipients: lactose monohydrate - 157 mg low substituted giproloza - 28 mg Povidone - 10 mg Magnesium stearate - 1 mg.
Composition of film-coating: Opadry Red 10 mg, incl hypromellose 2910 56%, 28% talc, macrogol-8000 - 10% titanium dioxide - 4%, iron oxide red dye - 2%...
Clinico-pharmacological group: anticonvulsants
Pharmaco-therapeutic group: anticonvulsants
Testimony
- As an aid in the treatment of partial seizures in patients with epilepsy aged 12 years and older, with or without secondary generalized seizures.
Dosage
Use in adults and adolescents
Perampanel taken orally 1 time a day at bedtime independently of food intake. The tablet must be swallowed whole, washed down with a glass of water 1. The tablet can not chew, crush or crumble, because the tablet can not be neatly separated, since there are no risks.
It was shown that the drug Faykompa at daily doses of from 4 to 12 mg is effective in the treatment of partial seizures. Admission Faykompa drug should be started at a dose of 2 mg per day. The dose may be increased according to clinical response, and tolerability of 2 mg increments not more than once per week up to 8.4 mg per day. Depending on individual clinical response, and tolerability of the drug in a dose of 8 mg per day may further increase drug Faykompa dose to 12 mg per day in increments of 2 mg not more than once per week. Despite the fact that perampanel has a long half-life, it is recommended, as for other AEDs, to abolish it gradually to minimize the likelihood of increasing seizure frequency.
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 administration of the drug.
If omitted receiving more than 1 dose (total duration of drug-free in less than 5 half-lives: 3 weeks for patients not receiving AEDs, altering metabolism of perampanel and 1 week for patients receiving AEDs, altering metabolism of perampanel) should consider 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 both at the initiation of treatment.
Use in children under 12 years
The safety and efficacy perampanel children under 12 years has not been established (see. "Contraindications").
Use in elderly patients (over 65 years)
In clinical studies, the drug involved Faykompa insufficient number of patients with epilepsy aged 65 years to assess the differences with younger patients. Analysis of safety information for patients taking perampanel did not reveal differences in the safety profile based on age. These data suggest that the dose correction perampanel depending on age is required. In elderly patients with perampanel should be used with caution (see. "Interaction with other medicinal products", "Special Instructions").
Use in patients with renal insufficiency
In renal insufficiency, mild perampanel dose adjustment is required. Application Faikompa drug in patients with moderate to severe renal impairment or in patients undergoing hemodialysis is not recommended (see. "Contraindications").
Use in patients with liver failure
Increasing doses in patients with liver failure mild and moderate, and as the other patients, is made depending on the clinical response and tolerability. Because liver failure mild to moderate half-life is prolonged perampanel, the minimum time interval prior to each dose escalation should be two weeks, and the maximum dose - not more than 8 mg per day. The use is not recommended (see. "Contraindications") with severe hepatic insufficiency.
Side effect
Among patients with partial seizures receiving perampanel in all clinical trials, 72% were treated for 6 months, and 43% - more than 12 months.
Adverse reactions, leading to the exit of patients from controlled studies III phase observed in the 1.7, 4.2 and 13.7% in patients treated perampanel, respectively, in doses of 4, 8 and 12 mg per day, and in 1.4% - in patients receiving placebo . The most common reasons for leaving the study were dizziness and somnolence (> 1% of the consolidated group perampanel than in the placebo group).
Listed below are adverse events (AEs), notes in the application perampanel, according to the system-organ class and frequency of occurrence. The following classification is used to estimate the frequency of occurrence of undesirable effects: very common (?1 / 10), commonly (?1 / 100, <1/10), uncommon (?1 / 1000, <1/100), rarely (? 000 1.10 <1/1000).
Eating disorders and metabolism: 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 of the organ of vision: often - diplopia, blurred vision.
Violations by the ear and labyrinth disorders: often - central vertigo.
Disorders of the gastrointestinal tract: often - nausea.
Violations of the musculoskeletal system and connective tissue disorders: often - back pain.
General disorders: often - gait disturbance, fatigue.
Laboratory and instrumental data: often - increased body mass.
Injury, poisoning and complications of manipulation: often - fall.
Teenagers
It can be expected that the incidence, nature and severity of adverse reactions in adolescents are the same as in adults based on clinical studies.
Contraindications
- Perampanel or hypersensitivity to any of the excipients of the drug,
- Pregnancy and lactation,
- Severe renal or hepatic insufficiency, patients on hemodialysis,
- Children under 12 years of age (efficacy and safety data are available)
- Galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Pregnancy and breast-feeding
Pregnancy
These perampanel for use in pregnant women are severely limited (less than 300 cases). In reproductive toxicity studies in animals direct or indirect toxic effects were found. As a precaution it is recommended to avoid the use of the drug during pregnancy Fycompa.
Period breastfeeding
In animal studies, it was shown that perampanel and / or its metabolites excreted in breast milk. It is not known whether perampanel is allocated to breast milk in humans, so the risk to the infant can not be excluded.
Given the advantages of breast-feeding for the child and care for a woman, you must either stop breast-feeding or to abstain from taking / stop taking Fycompa drug during breastfeeding.
Application for violations of liver function
Increasing doses in patients with liver failure mild and moderate, and as the other patients, is made depending on the clinical response and tolerability. Because liver failure mild to moderate half-life is prolonged perampanel, the minimum time interval prior to each dose escalation should be two weeks, and the maximum dose - not more than 8 mg per day. Use in severe hepatic impairment is not recommended.
Application for violations of renal function
In renal insufficiency, mild perampanel dose adjustment is required. Application Faikompa drug in patients with moderate to severe renal impairment or in patients undergoing hemodialysis is not recommended.
Use in children
The safety and efficacy perampanel children under 12 years has not been established
Use in elderly patients
In clinical studies, the drug involved Fycompa insufficient number of patients with epilepsy aged 65 years to assess the differences with younger patients. Analysis of safety information for patients taking perampanel did not reveal differences in the safety profile based on age. These data suggest that the dose correction perampanel depending on age is required. In elderly patients with perampanel should be used with caution
Special instructions
Suicide alertness
In patients taking AEDs for various reasons, 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 the present time it is impossible to exclude the possibility of increasing the risk and the application of Fycompa drug. Consequently, patients should be monitored to detect signs of suicidal thinking and behavior, it should be assigned the appropriate treatment. Patients or carers for them, should be informed of the need to seek medical attention if signs of suicidal ideation or behavior.
Contraception
Patients with intact reproductive function while receiving perampanel and at least 1 month after its termination, should use adequate contraception methods. While taking Fycompa the drug at a dose of 12 mg / day the effectiveness of hormonal contraceptives containing levonorgestrel can be reduced due to the likelihood of drug-drug interactions (see. "Interaction with other medicinal products" section). In these cases it is necessary to provide for the use of additional non-hormonal contraceptive methods.
Ending therapy
It is recommended to complete the therapy with Fycompa gradually in order to minimize the likelihood of increase in seizure frequency. In extreme cases, the possible sudden withdrawal of the drug, due to its long period of breeding and the relatively slow decline of its concentration in plasma following discontinuation.
Fall
The tendency, has no known cause to increase the number of falls, particularly in elderly patients,
Aggression
Cases of aggression, and their frequency was higher in patients treated with higher doses of the drug Faikompa. Most of these adverse events were mild or moderate and were both independently and at lower doses. In severe cases, the treatment of aggressive behavior had to stop. Thus, a rule must be strictly observed dose titration and use of its reduction, while maintaining the patient's symptoms of aggression.
The development of dependence
Caution should be exercised when administering the drug Faikompa patients with a history of drug dependence cases. Such patients should be observed for early detection of possible according to perampanel.
PEP (CYP3A inducer) Concomitant therapy
Efficiency perampanel fixed-dose was less in patients who received concomitant antiepileptic therapy CYP3A inducers (carbamazepine, phenytoin, oxcarbazepine) than in patients treated with AEDs fermeitno-inactive. 50% response rate to treatment perampanel 4 mg, 8 mg and 12 mg was respectively 23%, 31.5% and 30% in patients receiving probe CYP3A inducers, and, accordingly, 33.3%, 46.5 % and 50.0% of those patients who took enzymatically inactive AEDs. Effect perampanelom therapy should be carefully monitored when replacing or adding concomitant AEDs. Depending on individual clinical response to therapy, and tolerability, the dose can be increased or decreased in increments of 2 mg.
Effects on ability to drive vehicles and operate machinery
Faikompa has a moderate influence on the ability to drive and use machines. Perampanel may cause dizziness and somnolence and thereby affect the ability of management and use of transport mechanisms. Patients are advised not to drive vehicles, work with complex equipment or engage in other potentially hazardous activities until then, until it is clear whether perampanel affects their ability to perform these actions.
Overdose
Perampanel clinical experience of overdose in humans is limited. In the statement of intentional overdose that could result in doses up to 264 mg, the patient has a change of consciousness, agitation and aggressive behavior, the restoration took place without consequences.
There is no specific antidote. It shows the general supportive care, including monitoring vital signs and the patient's clinical status. Given poluvyvedsniya perampanel long period, its effects may have a longer duration of time. Because of low renal clearance perampanel conducting special procedures, such as forced diuresis, hemodialysis or hemoperfusion, ineffective.
Drug interactions
Oral contraceptives
At a dose of 12 mg per day perampanel decreased Cmax and area under the curve "concentration-time» (AUC) of levonorgestrel approximately 40%. Patients receiving the drug Fycompa should take into account the probability of reducing the effectiveness of contraceptives containing levonorgestrel, and use additional methods of contraception (vputrimatochnye drugs or condoms).
Ketoconazole
In healthy volunteers, at multiple dose ketoconazole, an inhibitor of isozyme CYP3A4, perampanel after a single dose of 1 mg T1 / 2poslednego increased by 15%, a AUC0-? - 20%.
cytochrome P450
It is believed that neither perampanel is a potent inhibitor of nor a potent inducer of cytochrome P450 isoenzymes. In drug interaction study in healthy volunteers have shown three-fold increase in clearance perampanel while the use of carbamazepine. In the population pharmacokinetic analysis of patients with partial seizures who received the placebo-controlled clinical trials, perampanel at daily doses up to 12 mg, observed a similar result.
Total clearance perampanel increased by concomitant use with carbamazepine (3-fold), phenytoin (2-fold) and oxcarbazepine (2-fold) - inducers of CYP3A4 isoenzyme. This effect should be taken into account when adding or canceling these AEDs in the treatment process.
Other potent inducers of cytochrome P450 isoenzymes, such as rifampicin, and St. John's wort, can also reduce the concentration of plasma perampanel. Felbamate can also reduce the plasma concentration perampanel.
The effect on both perampanel used AEDs
In the population pharmacokinetic analysis of patients with partial seizures treated with medication Faikompa at doses up to 12 mg per day during the placebo-controlled clinical studies, the reception perampanel little effect on the clearance of clonazepam, levetiracetam, phenobarbital, phenytoin, topiramate, and zonisamide. There was a statistically significant effect on the clearance of carbamazepine perampanel, klobazama, lamotrigine and valproic acid, at its value at the highest dose perampanel (12 mg daily) did not reach 10%. At the same time taking the drug Faikompa with oxcarbazepine, the last clearance was reduced by 26%.
In healthy volunteers a drug Fycompa reduced the AUC of midazolam by 13% and had no effect on Cmax or AUC of levodopa.
Use in Adolescents
drug interaction studies were conducted only in adults. In the population pharmacokinetic analysis of adolescents who participated in the Phase III clinical studies, there was no significant difference of the total study population.
Conditions of supply of pharmacies
On prescription.
Terms and Conditions of storage
Store at temperatures not above 30 ° C. Keep out of the reach of children. Shelf life - 5 years (for doses 2 and 4 mg) or 3 years (for dosages 6-8-10-12 mg).
