Perampanel (Fycompa) is a newly approved medication used to help control partial-onset seizures (with or without generalized seizures) when multiple drug therapy hasn't been successful. The drug should be added to existing therapy. Perampanel blocks specific glutamate receptors (glutamate is a neurotransmitter that stimulates the nervous system). It is the first antiepileptic drug that works solely in this manner, although precisely how it controls seizures isn't clearly understood. Clinical trials of perampanel, which is now approved for use in patients 12 years of age or older, showed a statistically significant reduction in seizures.

The most common adverse effects of the drug are dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, gait disturbance, and balance problems. Perampanel carries several serious warnings, including a boxed warning regarding the possibility of serious or life-threatening psychiatric and behavioral reactions such as aggression, hostility, irritability, anger, and homicidal ideation and threats. Patients are especially vulnerable during dosage escalation or when high doses of the drug are used. Common adverse neurologic effects, such as dizziness, gait disturbance, somnolence, and fatigue, may pose problems when the patient is driving or operating machinery and increase the likelihood of falls or injuries. Like all antiepileptic drugs, perampanel carries a warning that it may induce suicidal thoughts or behavior. There were four suicides in the active-treatment arms of the clinical trials studying perampanel and none in the placebo arms, but that number was too small for the Food and Drug Administration (FDA) to draw conclusions about the drug's effect on suicide. Perampanel has a very long half-life (105 hours), and the risk of adverse effects or drug interactions therefore persists for a while after discontinuation of the drug.

Perampanel is extensively metabolized through two isoenzymes in the cytochrome P-450 (CYP) enzyme system: CYP3A4 or CYP3A5. It can also weakly inhibit or induce other CYP isoenzymes. Several drug interactions related to the isoenzymes involved in the metabolism of perampanel are possible. Drugs that induce CYP3A, including other antiepileptic drugs such as carbamazepine, phenytoin, and oxcarbazepine, can decrease the circulating levels of perampanel by 50% to 67%. Higher doses of perampanel may be required, but there's no specific recommendation on how much to increase the dose. Coadministration with other inducers of CYP3A, such as the antitubercular drug rifampin and the over-the-counter herb St. John's wort, should be avoided. When given at the 12-mg dose, perampanel can lower circulating levels of oral contraceptives containing levonorgestrel enough to make them lose their therapeutic effectiveness.

The drug is taken once daily at bedtime. The recommended dosage (after titration) is 8 to 12 mg. A daily dosage of 12 mg greatly increases the risk of adverse effects. In clinical trials, serious adverse psychiatric and behavioral effects occurred in 20% of those receiving 12 mg, compared with 12% who received 8 mg, and 6% who received placebo. The recommended dosage may vary depending on which other antiepileptic medication is being taken concurrently and the patient's clinical responsiveness to the drug. Dosage increases should be made at weekly intervals; in older adults and patients with mild-to-moderate hepatic impairment, dosage increases should be made at two-week intervals. Patients with severe hepatic or renal impairment or who are on hemodialysis shouldn't be given perampanel.

Nurses should instruct patients to read the medication guide that accompanies each filled prescription for the most current information on potential serious adverse effects. Patients should be informed that perampanel can decrease the efficacy of oral contraceptives containing levonorgestrel and that they should use another form of birth control along with the oral contraceptive. Patients should be cautioned about the risk of sedation and instructed to avoid driving and operating complex machinery until they know how perampanel will affect them. Older adults, in particular, should take steps to prevent falls. Patients who miss a dose of perampanel should only take the next prescribed dose and not double up on the dose. Instruct patients not to suddenly stop taking perampanel, which could induce more seizures.

To read the FDA news release regarding perampanel's approval, go to http://1.usa.gov/Vw0hev.