Fycompa^® (Tablets, Suspension) Instructions for Use

ATC Code

N03AX22 (Perampanel)

Active Substance

Perampanel (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Anticonvulsant drug

Pharmacotherapeutic Group

Antiepileptic agents; other antiepileptic agents

Pharmacological Action

Anticonvulsant. It is believed that Perampanel reduces seizure activity by blocking excitatory signals in the brain.

Perampanel attaches to AMPA receptors on nerve cells and thereby blocks the action of glutamate, which normally plays a key role in transmitting excitatory signals from one nerve cell to another.

The exact mechanism of the anticonvulsant effect of perampanel in humans is subject to further study.

Pharmacokinetics

When taken orally, Perampanel is rapidly and completely absorbed; the first-pass effect through the liver is insignificant.

Food intake does not affect the extent of absorption but slows its rate.

Compared to taking on an empty stomach, simultaneous administration of the drug with food reduces the maximum plasma concentration of perampanel and increases the time to reach it by 2 hours.

Plasma protein binding is about 95%.

Perampanel is extensively metabolized by primary oxidation and subsequent glucuronidation.

According to in vitro studies with recombinant cytochrome P450 in human liver microsomes, primary oxidative metabolism is mediated by CYP3A isoenzymes.

However, the metabolism of perampanel is not yet fully understood, and other pathways cannot be excluded.

After administration of radioactively labeled perampanel, only trace amounts of its metabolites are detected in plasma.

After administration of radioactively labeled perampanel to healthy elderly volunteers, 30% of the radioactive label was found in urine and 70% in feces.

The excreted radioactive label mainly represented a mixture of oxidized and conjugated metabolites.

The mean T_1/2 of perampanel was 105 hours.

In healthy volunteers, perampanel plasma concentrations increased in direct proportion to the dose in the range from 2 to 12 mg.

In a population pharmacokinetic analysis of patients with partial seizures receiving Perampanel at doses up to 12 mg/day and patients with primary generalized tonic-clonic seizures receiving Perampanel at doses up to 8 mg/day in placebo-controlled clinical studies, a linear relationship was established between the dose and perampanel plasma concentration.

Indications

Treatment of epilepsy

As part of combination therapy for the treatment of partial seizures with or without secondary generalization in adults, adolescents aged 12 years and older, and children aged 4 to 11 years

Treatment of generalized seizures that cause convulsions or staring spells in adults, adolescents from 12 years and older, and children from 7 to 11 years.

ICD codes

Dosage Regimen

Take Fycompa^® orally once daily at bedtime.

Initiate treatment at 2 mg once daily. Increase the dose by 2 mg increments no more frequently than weekly based on individual clinical response and tolerability.

The maintenance dose for partial-onset seizures and primary generalized tonic-clonic seizures is 8 mg to 12 mg once daily.

For patients not taking concomitant enzyme-inducing AEDs, the maximum recommended daily dose is 12 mg.

For patients taking concomitant enzyme-inducing AEDs (e.g., carbamazepine, phenytoin), the maximum recommended daily dose is 16 mg due to increased perampanel clearance.

For pediatric patients aged 4 to 11 years with partial-onset seizures, use the oral suspension for accurate dosing. The recommended maintenance dose range is 8 mg to 12 mg once daily, based on body weight and clinical response.

For pediatric patients aged 7 to 11 years with primary generalized tonic-clonic seizures, the recommended maintenance dose range is 8 mg once daily.

For patients with mild or moderate hepatic impairment, the maximum recommended dose is 6 mg and 4 mg once daily, respectively. Contraindicated in severe hepatic impairment.

For patients with mild or moderate renal impairment, no dose adjustment is required. Contraindicated in severe renal impairment or patients on hemodialysis.

When discontinuing Fycompa^®, gradually reduce the dose. Avoid abrupt cessation due to the risk of increased seizure frequency.

Shake the oral suspension well before each use. Use the provided adapter and dosing syringe for administration.

Adverse Reactions

Very common dizziness, drowsiness.

Common increased or decreased appetite, weight gain, feeling of aggression, anger, anxiety, confusion, increased irritability, ataxia, gait disturbance, balance disorder, dysarthria, diplopia, vertigo, nausea, back pain, fatigue, falls.

Possible: DRESS syndrome, Stevens-Johnson syndrome.

Contraindications

Hypersensitivity to perampanel, severe renal failure, patients on hemodialysis, severe hepatic failure, pregnancy, breastfeeding period, children aged 4 to 11 years with body weight less than 30 kg.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindicated for use in severe hepatic impairment.

Use in Renal Impairment

Contraindicated for use in severe renal failure and in patients on hemodialysis.

Pediatric Use

Use in children under 4 years of age for the indication of partial seizures and in children under 7 years of age for the indication of generalized seizures is not recommended (safety and efficacy of perampanel have not been established to date).

Contraindicated for use in children aged 4 to 11 years with body weight less than 30 kg.

Geriatric Use

No effect of age on the clearance of perampanel was found.

Special Precautions

Cases of suicidal thoughts and behavior have been reported in patients taking anticonvulsant drugs for various indications.

The mechanism of increased risk is unknown, and the possibility of an increased risk with perampanel use cannot currently be excluded.

Therefore, patients should be monitored for the emergence of symptoms of suicidal thoughts and behavior; appropriate treatment should be prescribed.

Patients or their caregivers should be informed of the need to seek medical attention if signs of suicidal thoughts or behavior appear.

It is recommended to discontinue perampanel therapy gradually to minimize the potential for increased seizure frequency.

In extreme cases, abrupt discontinuation of the drug may be possible, taking into account its long elimination half-life and relatively slow decrease in plasma concentration after discontinuation.

Caution should be exercised when prescribing perampanel to patients with a history of drug dependence.

Such patients should be monitored for the timely detection of possible dependence on perampanel.

Effect on ability to drive vehicles and operate machinery

Perampanel has a moderate influence on the ability to drive vehicles and operate machinery.

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

Patients are advised not to drive vehicles, operate complex machinery, or engage in other potentially hazardous activities until it is known whether Perampanel affects their ability to perform these activities.

Drug Interactions

The efficacy of perampanel at fixed doses was lower in those patients who received concomitant therapy with CYP3A-inducing anticonvulsant drugs (carbamazepine, phenytoin, oxcarbazepine) than in patients receiving drugs that do not affect the activity of these isoenzymes.

The effect of perampanel therapy should be carefully monitored when concomitant AEDs are replaced or added.

The tolerability and effect of perampanel therapy should be carefully monitored when cytochrome P450 inducers or inhibitors are added or discontinued, as this may change the plasma concentration of perampanel and may require dose adjustment.

Some anticonvulsant drugs that are isoenzyme inducers (carbamazepine, phenytoin, oxcarbazepine) increase the total clearance of perampanel and accordingly reduce its plasma concentrations.

In a study involving healthy volunteers, carbamazepine, a known potent inducer of CYP450 isoenzymes, reduced the concentration of perampanel by two-thirds.

With simultaneous administration of perampanel and 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 the concentration of monohydroxycarbazepine is unknown.

In healthy volunteers, Perampanel (at a daily dose of 6 mg for 20 days) reduced the AUC of midazolam by 13%.

A more significant decrease in the exposure of midazolam (and other sensitive CYP3A substrates) with higher doses of perampanel cannot be excluded.

Potent inducers of cytochrome P450 isoenzymes, such as rifampicin and St. John’s wort, are also expected to reduce the plasma concentration of perampanel.

Felbamate may also reduce the plasma concentration of perampanel.

In healthy volunteers, administration of ketoconazole (at a daily dose of 400 mg for 10 days), an inhibitor of the CYP3A4 isoenzyme, increased the AUC of perampanel by 20% and prolonged its T_1/2 by 15% (67.8 h vs. 58.4 h).

When perampanel is combined with another CYP3A4 isoenzyme inhibitor with a T_1/2 longer than that of ketoconazole or with longer-term use of an inhibitor, an enhanced effect cannot be excluded.

Potent inhibitors of other cytochrome P450 isoenzymes may also potentially increase the concentration of perampanel.

While taking perampanel at a dose of 12 mg/day, the effectiveness of progestogen-containing hormonal contraceptives may be reduced.

In these cases, the use of additional non-hormonal methods of contraception should be provided.

In a pharmacodynamic interaction study in healthy volunteers, the effect of perampanel on alertness and reaction speed, such as driving a car, 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 is also observed when perampanel is taken in combination with other drugs that have a depressant effect on the CNS.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.