Overview
11 DESCRIPTION Perampanel tablets contain perampanel a non-competitive AMPA receptor antagonist as a 4:3 hydrate. The chemical name of the active ingredient is 2-(1´,6´-dihydro-6´-oxo-1´-phenyl[2,3´-bipyridin]-5´-yl)-benzonitrile, hydrate (4:3). The molecular formula is C 23 H 15 N 3 O ∙ ¾H 2 O, and the molecular weight is 362.90 (349.39 for anhydrous perampanel).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Perampanel is a non-competitive antagonist of the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons. Glutamate is the primary excitatory neurotransmitter in the central nervous system and is implicated in a number of neurological disorders caused by neuronal over excitation. The precise mechanism by which perampanel exerts its antiepileptic effects in humans is unknown. 12.2 Pharmacodynamics Psychomotor Performance In a healthy volunteer study to assess the effects of perampanel tablets on psychomotor performance using a standard battery of assessments including simulated driving, single and multiple daily doses of perampanel 4 mg did not impair simple psychomotor tasks,...
Indications
- 1 INDICATIONS AND USAGE Perampanel tablets, a non-competitive AMPA glutamate receptor antagonist, is indicated for: Treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 4 years of age and older ( 1.1 ) Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older ( 1.2 ) 1.1 Partial-Onset Seizures Perampanel tablets are indicated for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 4 years of age and...
Common Doses
- 2 mg
- 8 mg
- 12 mg
- 6 mg
Dosage
2 DOSAGE AND ADMINISTRATION Dosing in the absence of moderate or strong CYP3A4 inducers Starting dose: 2 mg once daily orally at bedtime ( 2.1 , 2.2 ) May increase dose based on clinical response and tolerability by increments of 2 mg once daily no more frequently than at weekly intervals ( 2.1 , 2.2 ) Recommended maintenance dose in monotherapy or adjunctive therapy for partial-onset seizures: 8 mg to 12 mg once daily at bedtime ( 2.1 ) Recommended maintenance dose in adjunctive therapy for primary generalized tonic-clonic seizures: 8 mg once daily at bedtime ( 2.
Black Box Warning
WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking perampanel ( 5.1). These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression ( 5.1).
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Serious Psychiatric and Behavioral Reactions [see Warnings and Precautions (5.1) ] Suicidal Behavior and Ideation [see Warnings and Precautions (5.2) ] Neurologic Effects [see Warnings and Precautions (5.3) ] Falls [see Warnings and Precautions (5.4) ] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. When moderate or strong CYP3A4 inducers are introduced or withdrawn, monitor patients closely. Dose adjustment of perampanel tablets may be necessary ( 2.3 , 7.2 ) 7.