How to gradually withdraw perampanel and introduce lacosamide?

Gradual Withdrawal of Perampanel and Introduction of Lacosamide

Withdraw perampanel by reducing the dose by 2 mg every 1-2 weeks while simultaneously introducing lacosamide at 50 mg twice daily, increasing by 50 mg twice daily at weekly intervals to a target maintenance dose of 200-400 mg daily. 1, 2

Perampanel Withdrawal Strategy

Tapering Schedule

• Reduce perampanel by 2 mg decrements at 1-2 week intervals until complete discontinuation 1, 2
• Due to perampanel's exceptionally long half-life of 105 hours, plasma concentrations decrease slowly even with abrupt cessation, effectively creating a self-tapering effect 3
• For patients on higher doses or with psychiatric concerns, consider extending the taper interval to 2-4 weeks between dose reductions to improve tolerability 4, 5

Critical Monitoring During Perampanel Withdrawal

• Monitor closely for psychiatric symptoms including aggression, hostility, irritability, and mood changes, as these are the most serious adverse effects associated with perampanel 2, 6
• Watch for increased seizure frequency after each dose reduction before proceeding to the next step 1
• Perampanel may remain detectable and clinically active for up to 3 weeks after discontinuation in some patients 3
• If withdrawal symptoms become severe, return to the previous well-tolerated dose and slow the taper further 1

Lacosamide Introduction Strategy

Initial Dosing and Titration

• Start lacosamide at 50 mg twice daily (100 mg/day total) 7
• Increase by 50 mg twice daily (100 mg/day total) at weekly intervals based on clinical response and tolerability 8
• Target maintenance dose is typically 200-400 mg daily in divided doses 8

Timing of Lacosamide Introduction

• Begin lacosamide when perampanel has been reduced to approximately 50% of the original dose, allowing overlap to maintain seizure control 1
• This cross-titration approach minimizes the risk of breakthrough seizures during the transition

Critical Safety Considerations

Cardiac Monitoring

• Obtain baseline ECG before starting lacosamide, as small dose-related increases in PR interval have been documented 8
• Monitor for cardiac conduction abnormalities, particularly in patients with pre-existing cardiac disease 8

Drug Interactions

• If the patient is taking moderate or strong CYP3A4 inducers (carbamazepine, oxcarbazepine, phenytoin), perampanel clearance will be increased, requiring closer monitoring during withdrawal 2
• Perampanel at 12 mg daily may decrease effectiveness of levonorgestrel-containing contraceptives 2

Common Pitfalls to Avoid

• Do not taper perampanel too rapidly (faster than 2 mg every 1-2 weeks), as this increases risk of withdrawal seizures despite the long half-life 1, 3
• Avoid abrupt discontinuation of perampanel in patients with severe psychiatric symptoms, as gradual withdrawal allows better symptom management 2, 4
• Do not assume perampanel is fully eliminated after stopping—it may remain active for 2-3 weeks, affecting assessment of lacosamide efficacy 3

Monitoring Parameters Throughout Transition

Seizure Control

• Document seizure frequency and type at baseline and after each medication adjustment 1
• If seizure frequency increases significantly, slow or pause the perampanel taper 1

Adverse Effects

• Perampanel-related: Monitor for dizziness, somnolence, ataxia, gait disturbance, and behavioral changes 2, 6, 4
• Lacosamide-related: Monitor for dizziness, PR interval prolongation, and nausea 8
• Neurological side effects (dizziness, somnolence) are common to both medications and may be additive during overlap 8, 6

Special Populations

• Elderly patients: Increase perampanel dose reductions no more frequently than every 2 weeks 2
• Hepatic impairment: Maximum perampanel dose should have been 6 mg (mild) or 4 mg (moderate); taper more slowly in these patients 2
• Renal impairment: Lacosamide requires dose adjustment in severe renal disease 8