Pharmacologic class: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist
Active ingredient: Perampanel 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg; tabs.
Indication: Adjunctive treatment of partial-onset seizures with or without secondarily generalized seizures in patients aged 12 years and older.
Pharmacology: Perampanel is a non-competitive antagonist of the ionotropic AMPA glutamate receptor on post-synaptic neurons.
The precise mechanism by which perampanel exerts its antiepileptic effects in humans has not been fully elucidated.
Clinical trials: The efficacy of perampanel in partial-onset seizures, with or without secondary generalization, was studied in patients aged 12 years and older who were not adequately controlled with one to three concomitant antiepileptic drugs in three randomized, double-blind, placebo-controlled, multicenter trials (Studies 1, 2, 3).
All trials had an initial six-week baseline period, during which patients were required to have more than five seizures. This was followed by a 19-week treatment period (six-week titration plus 13-week maintenance). Patients received an initial dos of 2 mg/day during the titration period, which was increased weekly by 2 mg/day to the final target dose.
The primary endpoint for all studies was the percent change in seizure frequency per 28 days during the treatment period as compared with the baseline period.
A statistically significant decrease in seizure rate was seen at doses of 4 mg/day to 12 mg/day (P <0.05). Dose response was apparent at 4 mg/day to 8 mg/day, with little additional benefit at 12 mg/day. Further analysis revealed a substantially reduced effect of perampanel with concomitant antiepileptic drug inducers (e.g., carbamazepine, oxcarbazepine [Trileptal], or phenytoin [Dilantin, Phenytek]).
The percentage of patients with a 40% to <60% reduction in seizure frequency during the maintenance phase were 13.2%, 17.4%, 19.0%, and 15.8% for placebo, 4 mg, 8 mg, and 12 mg, respectively. The percentages of patients with a ≥50% reduction in seizure frequency were 19.3%, 28.5%, 35.3%, and 35.0% for placebo, 4 mg, 8 mg, and 12 mg, respectively.
Adults: Initially 2 mg/day at bedtime; may increase by 2 mg/day in weekly increments to 4 mg/day to 12 mg/day; maximum 12 mg/day. Concomitant enzyme-inducing antiepileptic drugs: initially 4 mg/day at bedtime. Elderly or hepatic impairment: Maximum frequency for dose increase is every two weeks; mild: maximum 6 mg/day; moderate: maximum 4 mg/day. Severe hepatic or renal impairment, hemodialysis: not recommended.
Children: Not established.
Warnings/Precautions: Increased risk of serious psychiatric and behavioral reactions (e.g., aggression, hostility, irritability); monitor during treatment (especially initial titration period or at higher doses) and one month after last dose; reduce dose or permanently discontinue if symptoms persist. Increased risk of suicidal thoughts or behavior; monitor for clinical worsening or unusual changes.
Increased risk of neurologic effects (e.g., dizziness, gait disturbance, somnolence, fatigue) or falls and injuries; monitor (especially elderly). Avoid abrupt cessation. Elderly: titrate slowly. Pregnancy (Cat. C). Nursing mothers.
Interactions: Antagonized by CYP450 inducers (e.g., carbamazepine, phenytoin, oxcarbazepine [Trileptal], topiramate [Topamax]); monitor and may need dose adjustment. Avoid concomitant other strong CYP3A inducers (e.g., rifampin [Rifadin], St. John’s wort). Antagonizes midazolam (Versed). Potentiates oxcarbazepine. Potentiated by ketoconazole (Nizoral). Caution with concomitant central nervous system depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines) and alcohol. Reduces effectiveness of levonorgestrel (Next Choice, Plan B One-Step) (oral or implant contraceptives); use nonhormonal forms.
Adverse reactions: Dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, gait disturbance, balance disorder; psychiatric reactions.
Note: To enroll in the North American Antiepileptic Drug Pregnancy Registry, call 888.233.2334.
How supplied: Tabs— 30, 90
For more information,
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