FYCOMPA

What it is

Fycompa is perampanel (as hemisesquihydrate) supplied as film-coated tablets and oral suspension. Film-coated tablets are available in strengths of 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg. Oral suspension contains 2 mg perampanel per 4 mL. Perampanel is a first-in-class selective, non-competitive antagonist of the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) glutamate receptor on post-synaptic neurons.

Approved indications —

Partial-onset seizures (POS) with or without secondarily generalised seizures in patients from 4 years of age with epilepsy. — Primary generalised tonic-clonic seizures (PGTCS) in patients from 7 years of age with idiopathic generalised epilepsy.

Dosing overview

Fycompa must be titrated according to individual patient response in order to optimise the balance between efficacy and tolerability, and should be taken orally once daily at bedtime. Treatment should be initiated with the lowest dose specified for the patient's age and weight, with the dose increased based on clinical response and tolerability by increments (no more frequently than either weekly or every 2–4 weeks as per half-life considerations) to a maintenance dose. It is recommended that Fycompa is maintained at the lowest dose that controls symptoms in order to reduce potential adverse events.

Key safety warnings

Antiepileptic drugs, including Fycompa, increase the risk of suicidal thoughts or behaviour in patients taking these drugs for any indication. Patients treated with any antiepileptic drug should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviour, and/or any unusual changes in mood or behaviour. Pooled analyses showed that patients randomised to antiepileptic drugs had approximately twice the risk of suicidal thinking or behaviour compared to patients randomised to placebo, with an estimated incidence rate of 0.43% among drug-treated patients compared to 0.24% among placebo-treated patients. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including Fycompa. DRESS may be fatal or life-threatening. If signs or symptoms of DRESS are present, the patient should be evaluated immediately and Fycompa should be discontinued if an alternative aetiology for the signs or symptoms cannot be established. Fycompa caused dose-related increases in events related to dizziness and disturbance in gait or coordination. In controlled Phase 3 epilepsy clinical trials, dizziness and vertigo were reported in 35% and 47% of patients randomised to receive Fycompa at doses of 8 mg and 12 mg/day respectively, compared to 10% of placebo-treated patients. Gait disturbance related events were reported in 12% and 16% of patients randomised to receive Fycompa at doses of 8 mg and 12 mg/day respectively, compared to 2% of placebo-treated patients. An increased risk of falls, in some cases leading to serious injuries including head injuries and bone fracture, occurred in patients being treated with Fycompa. In controlled Phase 3 epilepsy clinical trials, falls were reported in 5% and 10% of patients randomised to receive Fycompa at doses of 8 mg and 12 mg/day respectively, compared to 3% of placebo-treated patients. In elderly patients, dizziness occurred in 55.6% of those given the 8 mg dose and 42.9% given the 12 mg dose. Falls occurred in 11.1% of elderly patients given the 8 mg dose and 57.1% given the 12 mg dose. Serious or life-threatening psychiatric and behavioural adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking Fycompa. Aggression was observed more frequently in adolescents than adults. In controlled Phase 3 epilepsy clinical trials, hostility and aggression related adverse reactions occurred in 12% and 20% of patients randomised to receive Fycompa at doses of 8 mg and 12 mg/day respectively, compared to 6% of patients in the placebo group. The combination of alcohol and Fycompa significantly worsened mood and increased anger. Patients taking Fycompa should avoid the use of alcohol.

Contraindications

Hypersensitivity to the active substance or to any of the excipients.

PBS listing

The document sources do not contain information about PBS listing, ex-manufacturer price, item numbers, or restriction type for Fycompa.

Regulatory history

Fycompa film-coated tablets (2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg) were first listed on the ARTG on 23 May 2014. Fycompa oral suspension (2 mg/4 mL) was first listed on the ARTG on 16 February 2021. In July 2017, the PBAC recommended Fycompa as new for the treatment of primary generalised tonic-clonic seizures in patients with idiopathic generalised epilepsy on the basis of a mixed comparison against placebo and other antiepileptic drugs for refractory patients. The TGA approved Fycompa on 11 February 2021 for the adjunctive treatment of partial-onset seizures in patients from 4 years of age and primary generalised tonic-clonic seizures in patients from 7 years of age, including a new oral suspension dosage form. This medicinal product is subject to additional monitoring in Australia due to approval of an extension of indications.