Drug Interaction Between Levetiracetam (Levipil) and Clonazepam
Levetiracetam and clonazepam can be safely used together without clinically significant drug interactions, and this combination is actually used therapeutically in clinical practice for seizure management. 1, 2
Evidence for Safety of Combined Use
Pharmacokinetic Profile
- No pharmacokinetic interactions exist between levetiracetam and clonazepam - neither drug alters the blood levels or metabolism of the other. 1
- A large randomized controlled trial (SAMUKeppra) specifically studied the combination of levetiracetam 2.5g plus clonazepam 1mg in 136 patients with status epilepticus and found no concerning drug-drug interactions. 1
- The adverse event profile was similar between groups receiving clonazepam alone versus clonazepam plus levetiracetam, with no additional safety concerns from the combination. 1
Clinical Use Evidence
- This combination is actively used in pediatric epilepsy treatment, where levetiracetam combined with short-term clonazepam effectively treats electrical status epilepticus during sleep in children with benign epilepsy, demonstrating both efficacy and safety. 2
- In 15 children treated with this combination, the therapy was well-tolerated with few side effects and good seizure control. 2
Pharmacodynamic Considerations
- Preclinical studies demonstrate that levetiracetam and clonazepam can produce synergistic (supra-additive) anticonvulsant effects at certain dose ratios (specifically 1:20,000 ratio), meaning they work together more effectively than either drug alone. 3
- At other dose ratios, the combination produces additive effects without adverse interactions. 3
- No adverse effects were observed in experimental models testing various combinations of these medications. 3
Important Clinical Monitoring
Sedation Risk
- Both medications can cause central nervous system depression, so monitor for excessive sedation, drowsiness, or respiratory depression, particularly when initiating therapy or adjusting doses. 4
- This is a pharmacodynamic consideration (additive CNS effects) rather than a true drug interaction. 4
Respiratory Monitoring
- When using these medications together, particularly in acute settings, be prepared to provide respiratory support and monitor oxygen saturation continuously. 5
- This precaution applies to the combined sedative effects rather than a specific interaction between the drugs. 5
Contrast with Other Antiepileptic Combinations
Unlike some other antiepileptic drug combinations, levetiracetam has a favorable interaction profile:
- Levetiracetam does not induce or inhibit hepatic enzymes, making it less prone to pharmacokinetic interactions compared to older antiepileptics. 6
- For comparison, levetiracetam can cause pharmacodynamic interactions with carbamazepine (increasing carbamazepine toxicity symptoms without changing blood levels), but this does not occur with clonazepam. 6
Clinical Bottom Line
You can safely prescribe levetiracetam and clonazepam together. The main consideration is monitoring for additive sedative effects rather than avoiding the combination due to drug interactions. This combination is evidence-based and used in both emergency status epilepticus treatment and chronic epilepsy management. 1, 2