Perampanel

Indications

Perampanel is used for: Perampanel an anti-epileptic drug is indicated for: Treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy from 4 years of age and older. Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients with epilepsy from12 years of age and older.

Adult Dose

Adult Oral Partial-onset seizures Initially 2 mg daily at bedtime. May be increased by increments of 2 mg (either wkly or every 2 wk) to a maintenance dose of 4-8 mg daily, w/ 1 wk interval between dose increases. Max dose: 12 mg daily. Primary generalised tonic-clonic seizures Initially 2 mg daily at bedtime. May be increased by increments of 2 mg (either wkly or every 2 wk) to a maintenance dose of 8 mg daily, w/ 1 wk interval between dose increases. Then, may be further increased up to 12 mg daily. Hepatic impairment Mild-to-moderate: 2 mg PO daily at bedtime. initially; increase by 2 mg/day increments no more frequently than q2weeks to target dose Mild (maximum dose): Not to exceed 6 mg/day Moderate (maximum dose): Not to exceed 4 mg/day Severe: Not recommended

Child Dose

Partial Onset Seizures Indicated as monotherapy or adjunctive therapy for partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy <4 years: Safety and efficacy not established >4 years Initial In absence of enzyme-inducing AEDs: 2 mg daily at bedtime; increase by 2 mg/day increments in at least weekly intervals to 4-8 mg daily at bedtime based on clinical response and tolerability Maintenance Dosage range: 8-12 mg/day Response may occur with 4mg/day; 12 mg/day resulted in greater seizure rate reductions and greater substantial increase in side effects Tonic Clonic Seizures Indicated as adjunctive therapy of primary generalized tonic-clonic seizures in patients with epilepsy <12 years: Safety and efficacy not established

Renal Dose

Renal impairment Moderate: May be used with close monitoring and slower titration Severe or hemodialysis: Not recommended

Administration

May be taken with or without food.

Contra Indications

Hypersensitivity.

Precautions

Serious psychiatric and behavioral reactions (eg, hostility, aggression) may emerge and appear to be dose related Antiepileptic drugs increase risk of suicidal thoughts or behavior; monitor for emergence or worsening of depression, suicidal thoughts or behavior, and unusual mood/behavior changes Dizziness, vertigo, and gait disturbances reported; monitor Somnolence and fatigue reported; caution patients against engaging in hazardous activities that require mental alertness Increased risk of falls

Pregnancy-Lactation

Pregnancy There are no adequate data on the developmental risk associated with use in pregnant women; in animal studies, perampanel induced developmental toxicity in pregnant rat and rabbit at clinically relevant doses Contraception Advise women who are using a levonorgestrel-containing contraceptive to use an additional non-hormonal form (eg, condoms) of contraception while in therapy and for a month after discontinuation Lactation Perampanel and/or its metabolites are present in rat milk, and are detected at concentrations higher than that in maternal plasma The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from therapy or from the underlying maternal condition

Interactions

Decreased levonorgestrel exposure. May decrease efficacy of progestative containing OCs. Increased clearance w/ CYP450 3A enzyme inducers eg, carbamazepine, phenytoin, oxcarbazepine. Reduced levels w/ carbamazepine. Decreased clearance of oxcarbazepine. Decreased AUC of midazolam. Decreased conc w/ strong CYP450 inducers eg, rifampicin & hypericum; felbamate. Increased AUC & prolonged t½ w/ ketoconazole. Additive or supra-additive effects of alcohol on tasks involving alertness & vigilance.

Side Effects

Side effects of Perampanel : >10% Dizziness (16-43%) Somnolence (9-18%) Headache (11-13%) Fatigue (8-12%) Irritability (4-12%) 1-10% Falls (2-10%) Nausea (6-8%) Ataxia (1-8%) Vertigo (3-5%) Balance disorder (3-5%) Back pain (2-5%) Weight gain (4%) Vomiting (2-4%) Anxiety (3-4%) Blurred vision (1-4%) Dysarthria (1-4%) Cough (1-4%) Hypoaesthesia (3%) Constipation (2-3%) Arthralgia (2-3%) Extremity pain (2-3%) Aggression (1-3%) Anger (1-3%) Myalgia (1-3%) Diplopia (1-3%) Injuries due to falls (1-3%) Hypersomnia (1-3%) Hyponatremia (2%) Contusions (2%) Oropharyngeal pain (2%) Asthenia (1-2%) Confusional state (1-2%) Euphoric mood (1-2%) Altered mood (1-2%) Abnormal coordination (1-2%) Musculoskeletal pain (1-2%) Peripheral edema (1-2%) Memory impairment (1-2%) Paraesthesia (1-2%)

Mode of Action

Noncompetitive antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons; glutamate is a primary excitatory neurotransmitter in the CNS and is implicated in various neurological disorders caused by neuronal over excitation.