How should I titrate down levetiracetam (Keppra) in a patient with a history of seizures and epilepsy, currently taking 1000 mg twice a day (BID), with normal renal function?

Gradual Tapering of Levetiracetam in Epilepsy Patients

Do not abruptly discontinue levetiracetam in patients with epilepsy—taper the dose gradually by reducing 500 mg every 1-2 weeks from the current 1000 mg BID (2000 mg/day total) to minimize seizure recurrence risk.

Recommended Tapering Schedule

Decrease by 500 mg increments every 1-2 weeks based on the standard titration guidance used when initiating levetiracetam, applied in reverse 1. This approach mirrors the upward titration protocol of 500 mg every 2 weeks to goal dosage, which has been established as well-tolerated 1.

Specific Tapering Protocol:

• Week 0-2: Continue 1000 mg BID (2000 mg/day total)
• Week 2-4: Reduce to 750 mg BID (1500 mg/day total) 1
• Week 4-6: Reduce to 500 mg BID (1000 mg/day total) 1
• Week 6-8: Reduce to 500 mg once daily (500 mg/day total) 1
• Week 8-10: Discontinue completely 1

Critical Monitoring During Taper

Monitor closely for breakthrough seizures at each dose reduction, as patients with epilepsy are at risk for seizure recurrence when antiepileptic medications are withdrawn 2. The half-life of levetiracetam is approximately 6-8 hours in adults with normal renal function, meaning steady-state at each new dose is achieved within 2 days 3.

• Assess seizure frequency at each follow-up visit to detect any increase in seizure activity 2
• Consider obtaining levetiracetam serum levels if breakthrough seizures occur to assess whether therapeutic levels are being maintained 2
• Watch for withdrawal-related seizures, particularly during the final stages of discontinuation 2

Renal Function Considerations

Since your patient has normal renal function, standard tapering applies without dose adjustment 3. However, 66% of levetiracetam is renally excreted unchanged, so if renal function changes during the taper, the schedule would need modification 3. In patients with impaired renal function, total body clearance decreases by 40-60% depending on severity, but this is not applicable to your patient 3.

Why This Tapering Approach

Abrupt discontinuation of antiepileptic drugs significantly increases seizure risk in patients with established epilepsy 2. The 500 mg every 1-2 week reduction is based on:

• The established titration schedule used when starting levetiracetam, which demonstrates good tolerability at this rate of change 1
• The pharmacokinetic profile showing rapid achievement of steady-state (2 days), allowing assessment of seizure control at each dose level 3
• Clinical experience showing that gradual tapers minimize withdrawal seizures compared to rapid discontinuation 2

Alternative Considerations

If breakthrough seizures occur during taper, hold at the current dose for an additional 2-4 weeks before attempting further reduction, or consider maintaining the patient on a lower maintenance dose rather than complete discontinuation 2. If seizures remain uncontrolled, escalation back to the previous effective dose is warranted 2.

The slower end of the range (2-week intervals) is preferable for patients with more severe epilepsy history or those who have had recent seizures, while faster tapering (1-week intervals) may be appropriate for patients with well-controlled seizures for extended periods 1, 2.