Ficompa, 2 mg 7 pcs

The drug Ficompa is indicated as an adjunctive treatment for partial seizures in patients with epilepsy aged 12 years and older in the presence or absence of secondary generalized seizures.

Indications

Fycompa is indicated as an adjuvant for the treatment of partial seizures in patients with epilepsy aged 12 years and older with or without secondary generalized seizures.

Pharmacological effect

Faycompa has an antiepileptic effect.

Special instructions

Suicidal alertness

Cases of suicidal ideation and behavior have been reported in patients taking AEDs for various indications. A meta-analysis of randomized placebo-controlled trials of AEDs also showed a small increase in the risk of suicidal ideation and behavior. The mechanism for the increase in risk is unknown; at present, the possibility of an increase in this risk with the use of the drug Fycompa cannot be excluded. As a result, patients should be monitored for symptoms of suicidal ideation and behavior; appropriate treatment should be prescribed.

Patients or their caregivers should be advised to seek medical attention if signs of suicidal ideation or behavior occur.

Nervous system disorders

Perampanel may cause dizziness and drowsiness and thereby affect the ability to drive and use machines.

Oral contraceptives

While taking Faycompa at a dose of 12 mg/day, the effectiveness of progestogen-containing hormonal contraceptives may be reduced (see section “Interaction with other drugs”). In these cases, it is necessary to consider the use of additional non-hormonal methods of contraception.

Completion of therapy

It is recommended to terminate therapy with Fycompa gradually in order to minimize the likelihood of an increase in the frequency of attacks. In extreme cases, abrupt discontinuation of the drug may be possible given its long elimination period and the relatively slow decline in plasma concentrations after discontinuation.

Falls

There has been a trend towards an increase in the number of falls, especially in older patients, the cause of which is unknown.

Aggression

Cases of aggressive and hostile behavior have been reported in patients receiving perampanel therapy. In clinical studies of perampanel, aggression, anger and irritability were more common when administered at higher doses. Most of these adverse events were mild or moderate in severity and resolved either independently or with dose reduction. However, thoughts of harming others, physical aggression, or threatening behavior have been observed in some patients (

Development of addiction

Caution must be exercised when prescribing Fycompa to patients with a history of drug dependence. Such patients should be monitored for timely detection of the development of possible dependence on perampanel.

Concomitant therapy with AEDs that induce the CYP3A isoenzyme

The effectiveness of perampanel in fixed doses was less in those patients who received concomitant antiepileptic therapy with inducers of the CYP3A isoenzyme (carbamazepine, phenytoin, oxcarbazepine) than in patients who received AEDs that do not affect the activity of enzymes. A 50% response to treatment with perampanel at a dose of 4, 8 and 12 mg was achieved, respectively, in 23, 31.5, and 30% of patients taking AEDs that induce the CYP3A isoenzyme, and, respectively, in 33.3, 46.5 and 50% of patients who took AEDs that do not affect enzyme activity. The effect of perampanel therapy should be carefully monitored when replacing or adding concomitant AEDs. Depending on the individual clinical response to treatment and tolerability of the drug, the dose may be increased or decreased in 2 mg increments.

Concomitant therapy with other inducers or inhibitors of cytochrome P450 isoenzymes that are not AEDs

The tolerability and effect of perampanel therapy should be carefully monitored when adding or removing inducers or inhibitors of cytochrome P450 isoenzymes, because this may alter the plasma concentration of perampanel and dose adjustment may be required.

Monotherapy

Within 28 days, seizures did not occur in 2–6.5% of those taking perampanel in clinical studies (0–1.7% in the placebo group). There is no information on the effect of discontinuing concomitant anticonvulsant therapy.

Impact on the ability to drive vehicles and operate machinery. Fycompa has a moderate effect on the ability to drive vehicles and operate machinery. Perampanel may cause dizziness and drowsiness and thereby affect the ability to drive and use machinery. Patients are advised not to drive vehicles, operate complex equipment, or engage in other potentially hazardous activities until it is determined whether perampanel affects their ability to perform these activities.

Active ingredient

Perampanel

Composition

1 tab. perampanel 2 mg

Excipients:

lactose monohydrate – 78.5 mg,

low-substituted hyprolose – 14 mg,

povidone – 5 mg,

magnesium stearate – 0.5 mg.

Film shell composition:

opadry orange – 5 mg (hypromellose 2910 – 56%, talc – 28%, macrogol 8000 – 10%, titanium dioxide – 4%, iron oxide yellow dye – 1.8%, iron oxide red dye – 0.2%).

Pregnancy

For women with preserved childbearing potential who do not use contraceptive methods, taking Fycompa is recommended only when absolutely necessary.

Data on the use of perampanel in pregnant women are significantly limited (

Animal studies have shown that perampanel and/or its metabolites are excreted in breast milk. It is unknown whether perampanel is excreted into breast milk in humans, so a risk to the baby cannot be excluded.

Given the benefits of both breastfeeding for the child and therapy for the woman, it is necessary to either stop breastfeeding or refrain from taking/discontinue taking Fycompa during breastfeeding.

Effect on fertility

In animal studies, it was shown that in high doses (30 mg/kg), perampanel prolongs and disrupts the regularity of the estrous cycle, but these changes did not affect fertility and early fetal development. No effect on male fertility was found. The effect of perampanel on human fertility has not been studied.

Contraindications

hypersensitivity to perampanel or any of the excipients of the drug;
galactose intolerance, lactase deficiency or glucose-galactose malabsorption;
severe renal or liver failure;
patients on hemodialysis;
pregnancy;
lactation period;
children under 12 years of age (no data on efficacy and safety).

Side Effects

Among 1639 patients with partial seizures who received perampanel in all clinical studies conducted, 1174 took the drug for 6 months and 703 for more than 12 months.

Adverse reactions leading to patient withdrawal from controlled phase III studies were observed in 1.7, 4.2 and 13.7% in patients receiving perampanel, respectively, at doses of 4, 8 and 12 mg/day, and in 1.4% in patients receiving placebo. The most common reasons for withdrawal from studies were dizziness and drowsiness (≥1% in the combined perampanel group and more than in the placebo group).

Listed below are the adverse events observed with the use of perampanel, according to systemic organ classes and their frequency of occurrence. To assess the incidence of adverse events, the following classification is used: very often (≥1/10); often (≥1/100,

Nutritional and metabolic disorders: often – decreased appetite, increased appetite.

Mental disorders: often – aggression, anger, anxiety, confusion.

Nervous system disorders: very often – dizziness, drowsiness; often – ataxia, dysarthria, imbalance, increased irritability.

Visual disturbances: often – diplopia, blurred vision.

Hearing and labyrinthine disorders: often – central vertigo.

Gastrointestinal disorders: often – nausea.

Disorders of the musculoskeletal system and connective tissue: often – back pain.

General disorders: often – gait disturbance, fatigue.

Laboratory and instrumental data: often – increased body weight.

Injuries, intoxications and complications of manipulations: often – falls.

Teenagers. Based on clinical trial data, it can be expected that the frequency, nature and severity of adverse reactions in adolescents are the same as in adults.

Interaction

Fycompa is not a potent inducer or inhibitor of cytochrome P450 isoenzymes or the UGT isoenzyme involved in glucuronidation reactions.

Oral contraceptives

At a dose of 12 mg/day (but not 4 or 8 mg/day), perampanel reduced the Cmax and AUC of levonorgestrel by approximately 40%. Perampanel at a daily dose of 12 mg has no effect on the AUC of ethinyl estradiol, but reduces its Cmax by 18%. Patients taking Fycompa should be aware of the possibility of reduced effectiveness of contraceptives containing levonorgestrel and use additional methods of contraception (intrauterine devices or condoms).

Interaction with other antiepileptic drugs (AEDs)

The potential interaction between Fycompa (at a single daily dose of up to 12 mg) and other AEDs was assessed based on clinical trial data and population pharmacokinetic analysis of pooled data from three phase III studies. The effect of this interaction on the equilibrium concentrations of PEP is given in the table:

Table

Co-administered AEDs The effect of AEDs on the concentration of the drug Faicompa The effect of the drug Faicompa on the concentration of AEDs Carbamazepine Reduction by » 70% Reduction by less than 10% Clobazam No effect Reduction by less than 10% Clonazepam No effect No effect Lamotrigine No effect Reduction by less than 10% Levetiracetam No effect No effect influenceOxcarbazepineDecrease by »50%Increase by 35% *PhenobarbitalNo effectNo effectPhenytoinDecrease by »50%No effect TopiramateDecrease by 20%No effectValproic acidNo effectDecrease by less than 10%ZonisamideNo effectNo effect

* Excluding the active metabolite monohydroxycarbazepine.

Some AEDs that are enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) increase the overall clearance of perampanel and accordingly reduce its plasma concentrations.

In a study involving healthy volunteers, carbamazepine, a known potent enzyme inducer, reduced perampanel concentrations by 2/3 (3-fold).

A similar result was obtained in a population pharmacokinetic analysis in patients with partial-onset seizures treated with Fycompa at doses up to 12 mg/day in placebo-controlled clinical trials. Taking Fycompa did not have a clinically significant effect on the clearance of clonazepam, levetiracetam, phenobarbital, phenytoin, topiramate, zonisamide, carbamazepine, clobazam, lamotrigine and valproic acid, at the highest dose of perampanel (12 mg/day).

When taking the drug perampanel simultaneously with oxcarbazepine, the clearance of the latter decreased by 26%. Oxcarbazepine is rapidly metabolized by cytosolic reductase to the active metabolite monohydroxycarbazepine. The effect of perampanel on monohydroxycarbazepine concentrations is unknown.

The dose of perampanel is adjusted until a clinical effect is achieved, regardless of concomitant AEDs.

Effect of perampanel on substrates of the CYP3A isoenzyme

In healthy volunteers, Fycompa (daily dose of 6 mg for 20 days) reduced the AUC of midazolam by 13%. A greater reduction in exposure to midazolam (and other sensitive CYP3A substrates) when taking higher doses of Fycompa cannot be excluded.

The influence of inducers of cytochrome P450 isoenzymes on the pharmacokinetics of perampanel

It is expected that potent inducers of cytochrome P450 isoenzymes, such as rifampicin and St. John’s wort, may also reduce plasma concentrations of perampanel. Felbamate may also decrease plasma concentrations of perampanel.

Effect of inhibitors of cytochrome P450 isoenzymes on the pharmacokinetics of perampanel

In healthy volunteers, taking ketoconazole (at a daily dose of 400 mg for 10 days), which is an inhibitor of the CYP3A4 isoenzyme, increased the AUC of perampanel by 20% and prolonged its T1/2 by 15% (67.8 versus 58.4 hours). When perampanel is combined with another inhibitor of the CYP3A4 isoenzyme with a half-life longer than that of ketoconazole or with a longer administration of the inhibitor, an enhanced effect cannot be ruled out. Potent inhibitors of other cytochrome P450 isoenzymes may also potentially increase perampanel concentrations.

Interaction with levodopa

In healthy volunteers, administration of Fycompa (at a daily dose of 4 mg for 19 days) had no effect on the AUC or Cmax of levodopa.

Interaction with alcohol

In a pharmacodynamic interaction study in healthy volunteers, the effect of perampanel on alertness and reaction time, such as driving, was enhanced by alcohol intake. Repeated administration of perampanel at a daily dose of 12 mg increased the severity of irritability, confusion and depression. This effect has also been observed when Fycompa is taken in combination with other CNS depressants.

Use in adolescents

Drug interaction studies were conducted in adults only. In a population pharmacokinetic analysis, adolescents participating in phase III clinical trials showed no significant differences from the general study population.

Overdose

Symptoms: Clinical experience with perampanel overdose in humans is limited. In a report of an intentional overdose that could have resulted in doses up to 264 mg, the patient experienced altered consciousness, agitation, and aggressive behavior; recovery was without consequences.

Treatment: There is no specific antidote. General supportive therapy is indicated, including monitoring of the patient’s vital signs and clinical status. Given the long T1/2 of perampanel, its effects may have a longer duration. Due to the low renal clearance of perampanel, special procedures such as forced diuresis, hemodialysis or hemoperfusion are ineffective.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

4 years

Manufacturer

Eisai, Japan