- Design
- Observational hospital cohort using salvaged clinical blood samples
- Population
- 77 inpatients on apixaban for ≥72 hours, with or without levetiracetam
- Primary outcome
- Apixaban Cmin and Cmax
- Effect
- No apparent difference in Cmin or Cmax with levetiracetam (medians marginally higher)
Some professional bodies have advised caution when apixaban and levetiracetam are co-prescribed, although there is no clear mechanism: levetiracetam is not a significant CYP3A4 or P-glycoprotein inducer or inhibitor, and the apixaban label carries no warning.
Investigators identified hospital patients who had taken apixaban for at least 72 hours, with or without levetiracetam, and measured apixaban trough and peak concentrations in 77 salvaged clinical blood samples. Median concentrations were marginally higher with levetiracetam but showed no apparent difference from apixaban alone.
This matters because the combination is common — older patients with atrial fibrillation often have seizures after stroke — and misplaced caution can lead to switching to a less suitable anticonvulsant, such as enzyme-inducing carbamazepine or phenytoin, that genuinely lowers apixaban levels. The study is small and descriptive, but it is consistent with the pharmacology.
- Levetiracetam can be co-prescribed with apixaban; no interaction was apparent in measured levels.
- Avoid enzyme-inducing anticonvulsants (carbamazepine, phenytoin, phenobarbital) with apixaban — these do lower DOAC levels.
- In post-stroke epilepsy on a DOAC, levetiracetam is a reasonable first choice from an interaction standpoint.
- Adjust levetiracetam for renal function, which also matters for apixaban dosing.
Why it matters
It removes a caution that could push prescribers toward anticonvulsants that genuinely interact with DOACs.
Don't overread it
A small descriptive study using salvaged samples, not a formal interaction study — it shows no apparent effect, not proof of none.
The statistics, in plain English
With 77 patients and descriptive statistics only, the study could miss a small interaction; but a large, clinically important change in apixaban levels would probably have been visible.
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