Can Levetiracetam and Lamotrigine Be Taken Together for Epilepsy?
Yes, levetiracetam and lamotrigine can be safely taken together for epilepsy, and routine therapeutic drug monitoring is not required for either medication. 1, 2
Combination Therapy Safety and Efficacy
Levetiracetam and lamotrigine have no significant pharmacokinetic interactions with each other. The FDA label for levetiracetam explicitly states that it does not affect plasma concentrations of lamotrigine, and lamotrigine does not influence levetiracetam pharmacokinetics. 2
This combination may actually be synergistic. Research suggests a possible beneficial pharmacodynamic interaction between levetiracetam and lamotrigine, with lamotrigine being used significantly more often in combination with levetiracetam in patients who achieved seizure freedom (p = 0.003). 3
Both drugs are recommended as first-line agents by EANO-ESMO guidelines due to their efficacy and overall good tolerability, making their combination a rational choice. 1
Therapeutic Drug Monitoring Requirements
Neither levetiracetam nor lamotrigine requires routine therapeutic drug monitoring. 1
When to Consider Monitoring:
Serum levels can be checked to assess compliance if seizure control fails unexpectedly. 1
Levels may help differentiate drug-related side effects from other causes of symptoms. 1
Routine laboratory monitoring is not systematically required, though levetiracetam has been associated with relatively infrequent abnormalities in hematologic parameters and liver function tests. 2
Clinical Considerations for This Combination
Dosing Strategy:
Levetiracetam can be started at therapeutic doses immediately (typically 500-1000 mg twice daily), as it does not require titration. 2
Lamotrigine requires slow titration over several weeks to minimize rash risk, with target maintenance doses of 200-400 mg daily in divided doses. 4
Responders to levetiracetam often achieve seizure control at relatively low doses (mean daily dose lower in responders than non-responders). 3
Adverse Event Profile:
Levetiracetam may cause behavioral changes including aggression, agitation, anger, anxiety, depression, and irritability; patients should report these immediately. 2
Lamotrigine's main concern is rash risk, which is minimized by slow titration and avoiding rapid dose escalation. 4
Both drugs can cause dizziness and somnolence, though continued administration does not result in clinically meaningful driving impairment. 1
Drug Interaction Profile
This combination has minimal drug interaction concerns:
Levetiracetam circulates largely unbound (<10% bound) to plasma proteins, making clinically significant protein-binding interactions unlikely. 2
Levetiracetam is not an inhibitor or substrate of cytochrome P450 enzymes, epoxide hydrolase, or UDP glucuronidation enzymes. 2
No dose adjustments are needed when combining these medications. 2
Common Pitfall to Avoid
Do not rapidly titrate lamotrigine when adding it to levetiracetam, as this significantly increases rash risk regardless of the concomitant medication. 4 Follow standard lamotrigine titration schedules even when the patient is already on levetiracetam.