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.

Active ingredient

Composition

1 tablet perampanel 2 mg

Associated substances:

lactose monohydrate – 78.5 mg,

low-substituted hyprolose – 14 mg,

povidone – 5 mg,

magnesium stearate – 0.5 mg.

Composition of the film coating:

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

How to take, the dosage

Ingestion, before bedtime, regardless of meals.

Application in adults and adolescents. Perampanel is taken once a day. The tablet must be swallowed whole with 1 glass of water, and must not be chewed, crumbled or broken because the tablet cannot be neatly separated because there is no risk on it.

Faicompa in daily doses of 4 to 12 mg has been shown to be effective in the treatment of partial epileptic seizures. Administration of Ficompa should be started with a dose of 2 mg/day. The dose may be increased depending on clinical response and tolerability, in increments of 2 mg no more than once a week, to 4-8 mg/day. Depending on individual clinical response and tolerability, a dose of 8 mg/day may be further increased to 12 mg/day, in 2 mg increments no more than once a week. In patients concomitantly receiving PEPs that do not reduce the half-life of perampanel, the dose of perampanel should be adjusted at two-week intervals. In patients concomitantly receiving PEPs that decrease the half-life of perampanel, the dose of perampanel should be increased once a week.

The drug should be withdrawn gradually.

Only missed doses: because of the long T1/2 of perampanel, patients should wait and take the next planned dose according to the agreed dosing schedule.

If more than 1 dose is missed (total duration without medication less than 5T1/2: 3 weeks for patients not receiving PEPs that alter the metabolism of perampanel and 1 week for patients receiving PEPs that alter the metabolism of perampanel), consider resuming the drug at the last dose taken.

If the patient has interrupted the medication for more than 5T1/2, the recommendations should be followed as when initiating treatment.

The use in children younger than 12 years of age. The safety and effectiveness of perampanel in children younger than 12 years has not been established.

The use in elderly patients (≥65 years). Insufficient numbers of patients with epilepsy over 65 years of age have been enrolled in clinical trials of Ficompa to evaluate differences with younger patients. An analysis of safety information in 905 elderly patients taking perampanel showed no differences in safety profile by age. These data confirm that there is no need to adjust the dose of perampanel according to age. Perampanel should be used with caution in elderly patients.

The use in patients with renal insufficiency. In patients with mild renal insufficiency, correction of the perampanel dose is not required. The use of Ficompa in patients with moderate to severe renal failure or patients on hemodialysis is not recommended.

The use in patients with hepatic impairment. Increase the dose in patients with mild to moderate hepatic impairment, as in other patients, depending on clinical response and tolerability. Since in mild to moderate hepatic insufficiency the T1/2 of perampanel is prolonged, the minimum time interval before each dose increase should be 2 weeks, and the maximum dose should not exceed 8 mg/day. Use in severe hepatic impairment is not recommended.

Interaction

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

Perampanel at a dose of 12 mg/day (but not 4 or 8 mg/day) reduced Cmax and AUC of levonorgestrel by approximately 40%. Perampanel at a daily dose of 12 mg had no effect on the AUC of ethinylestradiol, but reduced its Cmax by 18%. Patients taking Ficompa should consider the possibility of decreased efficacy of contraceptives containing levonorgestrel and use additional methods of contraception (intrauterine devices or condoms).

Interaction with other antiepileptic drugs (AEDs)

The potential interaction of Ficompa (with a single daily dose up to 12 mg) and other AEDs has been evaluated based on data from clinical trials and population pharmacokinetic analysis of pooled data from three phase III studies. The effect of this interaction on equilibrium concentrations of PEPs is shown in the table:

Table

. Co-administered PEPEffect of PEP on Ficomp drug concentrationFicomp drug effect on PEP concentrationCarbamazepineDecrease by “70%Decrease by less than 10%ClobazamNo effectDecrease by less than 10%ClonazepamNo effectNo effectLamotrigineNo effectDecrease by less than 10%LevetiracetamNo effectNo effectOxcarbazepineNo effectDecrease by “50% Increase by 35% *PhenobarbitalNo effectPhenytoinNo effectDecrease by “50%No effectTopiramateDecrease by 20%No effectValproic acidNo effectDecrease by less than 10%ZonisamideNo effect

* Excluding the active metabolite monohydroxycarbazepine.

Some PEDs that are enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) increase total clearance of perampanel and decrease its plasma concentrations accordingly.

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-based pharmacokinetic analysis in patients with partial seizures receiving Ficompa at doses up to 12 mg/day in placebo-controlled clinical trials. Administration of Ficompa had no 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 perampanel was taken concomitantly with oxcarbazepine, the latter’s clearance was decreased by 26%. Oxcarbazepine is rapidly metabolized with cytosolic reductase to the active metabolite monohydroxycarbazepine. The effect of perampanel on monohydroxycarbazepine concentrations is unknown.

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

The effect of perampanel on CYP3A isoenzyme substrates

In healthy volunteers, Ficompa (at a 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 isoenzyme substrates) cannot be excluded with higher doses of Ficompa.

The effect of cytochrome P450 isoenzyme inducers on the pharmacokinetics of perampanel

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

The effect of cytochrome P450 isoenzyme inhibitors on the pharmacokinetics of perampanel

. In healthy volunteers, administration of ketoconazole (daily dose of 400 mg for 10 days), which is an inhibitor of CYP3A4, increased AUC of perampanel by 20% prolonged its T1/2 by 15% (67.8 vs 58.4 h). When combining perampanel with another CYP3A4 isoenzyme inhibitor with a longer half-life than ketoconazole or when taking the inhibitor for a longer time, an increased effect cannot be excluded. Powerful inhibitors of other cytochrome P450 isoenzymes can also potentially increase the concentration of perampanel.

Interaction with levodopa

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

In an interaction with alcohol

In a pharmacodynamic interaction study on healthy volunteers, the effect of perampanel on attention and responsiveness, such as driving, was enhanced by alcohol intake. Repeated administration of perampanel at a daily dose of 12 mg and increased the severity of irritability, confusion and depression. This effect was also observed when taking Ficompa in combination with other CNS depressants.

The use in adolescents

Drug interaction studies have only been conducted in adults. In population pharmacokinetic analyses in adolescents who participated in phase III clinical trials, there were no observable differences from the general study population.

Special Instructions

Suicidal ideation

Suicidal ideation and behavior have been reported in patients taking PEPs for various indications. A meta-analysis of randomized placebo-controlled trials of PEPs also showed a small increase in the risk of suicidal thinking and behavior. The mechanism of the increased risk is unknown; at this time, the possibility of an increase in this risk cannot be ruled out with Ficomp as well. As a consequence, patients should be monitored for symptoms of suicidal thinking and behavior; appropriate treatment should be prescribed.

Patients or their caregivers should be informed to seek medical attention when signs of suicidal thinking or behavior appear.

Nervous system disorders

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

Perhaps with Ficompa at a dose of 12 mg/day, the effectiveness of progestagen-containing hormonal contraceptives may be reduced (see section “Interaction with other medicinal products”). In these cases, the use of additional non-hormonal contraceptive methods should be considered.

The termination of therapy

It is recommended that therapy with Ficompa be terminated gradually to minimize the likelihood of increased seizure frequency. In extreme cases, abrupt discontinuation of the drug is possible, given its long elimination time and relatively slow decline in plasma concentrations after discontinuation.

Falls

There has been a tendency for an increase in falls, especially in elderly patients, the cause of which is unknown.

Aggression

Incidents of aggressive and hostile behavior have been reported in patients receiving perampanel therapy. In clinical trials of perampanel, aggression, anger, and irritability occurred more frequently when used at higher doses. Most of these adverse events were mild to moderate in severity and went away either on their own or when the dose was reduced. However, thoughts of harming others, physical aggression or threatening behavior have been seen in some patients (

Dependence development

Patients with a history of drug dependence should be advised when prescribing Ficompa. These patients should be monitored for early detection of possible perampanel dependence.

Companion therapy with PEPs inducing CYP3A isoenzyme

Efficacy of perampanel in fixed doses was lower in those patients who received concomitant antiepileptic therapy with CYP3A isoenzyme inducers (carbamazepine, phenytoin, oxcarbazepine) than in patients who received PEPs not affecting enzyme activity. 50% response on perampanel therapy in doses of 4, 8 and 12 mg was achieved in 23, 31.5, and 30% of patients receiving PEPs inducing CYP3A isoenzyme and, respectively, in 33.3, 46.5 and 50% of patients receiving PEPs not affecting enzyme activity. The effect of perampanel therapy should be closely monitored when concomitant PEPs are replaced or added. Depending on the individual clinical response to treatment and tolerability of the drug, the dose may be increased or decreased in 2 mg increments.

Companion therapy with other cytochrome P450 isoenzyme inducers or inhibitors that are not PEPs

The tolerability and effect of therapy with perampanel should be closely monitored when adding or withdrawing cytochrome P450 inducers or inhibitors, as this may alter the concentration of the drug.as this may alter the plasma concentration of perampanel and dosage adjustment may be required.

Monotherapy

At 28 days, seizures did not occur in 2-6.5% of those taking perampanel in the clinical trials (0-1.7% in the placebo group). There are no data on the effect of withdrawal of concomitant anticonvulsant therapy.

The effect on the ability to drive vehicles and operate mechanisms. Ficompa has a moderate effect on the ability to drive vehicles and operate mechanisms. Perampanel may cause dizziness and somnolence and thereby affect the ability to drive vehicles and operate mechanisms. 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.

Contraindications

Side effects

Among the 1,639 patients with partial seizures who received perampanel in all of the clinical trials conducted, 1,174 took the drug for 6 months and 703 for more than 12 months.

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

The adverse events reported with perampanel are listed below according to systemic organ class and frequency of occurrence. The following classification is used to estimate the incidence of adverse events: very common (≥1/10); common (≥1/100,

Eating and metabolic disorders: common – decreased appetite, increased appetite.

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

Nervous system disorders: very often – dizziness, somnolence; often – ataxia, dysarthria, loss of balance, increased irritability.

Visual organ disorders: often – diplopia, blurred vision.

Hearing and labyrinth disorders: often – central vertigo.

Gastrointestinal disorders: often – nausea.

Skeletal and muscular system and connective tissue disorders: often – back pain.

General disorders: often – gait disturbance, fatigue.

Laboratory and instrumental data: often – weight gain.

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

Adolescents. Based on data from clinical studies, the frequency, nature, and severity of adverse reactions in adolescents can be expected to be the same as in adults.

Overdose

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

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

Pregnancy use

Women of preserved childbearing potential who are not using contraceptive methods are advised to take Ficompa only if absolutely necessary.

The data on the use of perampanel in pregnant women are considerably limited (

In animal studies, it has been shown that perampanel and/or its metabolites are excreted with breast milk. It is not known whether perampanel is excreted with breast milk in humans, so the risk to the baby cannot be ruled out.

With the benefits of both breastfeeding for the baby and therapy for the woman, it is necessary to either stop breastfeeding or to refrain from taking/stop taking Ficomp while breastfeeding.

Effects on fertility

In animal studies, perampanel has been shown to prolong and disrupt the regularity of the estrous cycle at high doses (30 mg/kg), but these changes had no effect on fertility or early fetal development. No effect on male fertility was found. The effect of perampanel on human fertility has not been studied.