Generic Name

Perampanel

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Classification

FDA Approved Indications

• Partial-onset seizures with or without secondarily generalized seizures in patients 4 years and older
• Primary generalized tonic-clonic seizures in patients 12 years and older

Mechanism of Action

Perampanel is a selective, non-competitive antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, which inhibits excitatory neurotransmission mediated by glutamate, reducing seizure activity.

Dosage and Administration

Adult: Initial dose: 2 mg once daily at bedtime, titrate up in 2 mg increments weekly to a target dose of 8-12 mg daily, as tolerated.

Pediatric: Starting dose varies based on age and concomitant medications; typically 2 mg at bedtime, titrated as needed.

Geriatric: Start at the lower end of the dosing range, with cautious titration, considering comorbidities and concomitant medications.

Renal Impairment: No dose adjustment recommended for mild to moderate impairment; data limited for severe impairment.

Hepatic Impairment: Use with caution; consider starting at lower doses due to potential increased sensitivity.

Pharmacokinetics

Absorption: Rapidly absorbed, with peak plasma concentrations reached approximately 0.5-2 hours after administration.

Distribution: High protein binding (~85%), primarily to albumin.

Metabolism: Metabolized mainly by CYP3A4/5 enzymes.

Excretion: Primarily excreted in urine and feces as metabolites.

Half Life: Approximately 105 hours, supporting once-daily dosing.

Contraindications

• Known hypersensitivity to perampanel or any component of the formulation.

Precautions

• Use with caution in patients with a history of psychiatric disorders, including depression, psychosis, and suicidal thoughts; monitor closely.
• Potential for cognitive and psychiatric adverse effects; dose adjustments may be necessary.

Adverse Reactions - Common

• Dizziness (Often)
• somnolence (Often)
• fatigue (Often)
• irritability (Often)
• gait disturbance (Often)

Adverse Reactions - Serious

• Serious neuropsychiatric events (e.g., aggression, hostility, irritability, homicidal thoughts) (Less common but serious)
• Severe hypersensitivity reactions (Rare)

Drug-Drug Interactions

• CYP3A4 inducers (e.g., carbamazepine, phenytoin) may decrease perampanel levels; co-administration may require dose adjustments.
• CYP3A4 inhibitors (e.g., ketoconazole) may increase perampanel levels.
• Other CNS depressants may have additive sedative effects.

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Explain the purpose of the medication and the importance of adherence.
• Warn about potential side effects like dizziness, somnolence, mood changes, andBehavioral effects.
• Advise to avoid alcohol and CNS depressants.
• Encourage report of mood changes, agitation, or suicidal thoughts.

Special Considerations

Black Box Warnings:

• Serious neuropsychiatric events, including aggression, hostility, and suicidal thoughts and behaviors, have been reported.
• Patients should be closely monitored, especially during initiation and titration.

Genetic Factors: Pharmacogenetic testing is not routinely required.

Lab Test Interference: None known.

Overdose Management

Signs/Symptoms: Dizziness, somnolence, ataxia, agitation, hallucinations, somnolence, coma in severe cases.

Treatment: Supportive care; gastric decontamination if recent ingestion; activated charcoal if within 1 hour of ingestion; hemodialysis is not effective due to high protein binding.

Storage and Handling

Storage: Store at room temperature between 20°C to 25°C (68°F to 77°F).

Stability: Stable up to the expiration date when stored properly.