DDDR-35 Thrombotic event occurrence in patients treated with concurrent apixaban and levetiracetam

Current guidelines for patients with brain tumors list levetiracetam as a first-line treatment for seizures and apixaban as the preferred agent for therapeutic anticoagulation of cancer-associated VTE. A pharmacovigilance study has suggested a signal for interaction between levetiracetam and apixaban, possibly due to P-glycoprotein induction by levetiracetam, but there has been mixed evidence for increased risk of thromboembolic events in co-administration with apixaban. The purpose of the study was to determine whether patients taking levetiracetam and apixaban have an increased risk of thrombotic events. We evaluated thrombotic event occurrence retrospectively in 169 adult patients (49.1% female, average age 66.2 years, range 25-94 years) concurrently prescribed levetiracetam and apixaban between January 2020 and December 2025), 18.3% (31/169) of whom were undergoing active cancer treatment. Nineteen patients (11%) experienced a thrombotic event, including stroke (11/19), PE (8/19), and DVT (1/19), compared to the recurrent risk of breakthrough thrombotic events on apixaban documented at 1.3% in the general population and about 6% of the cancer population. Longer overlap period of concurrent levetiracetam and apixaban was significantly associated with increased risk of thrombotic event, with patients on both medications for more than 28 months being significantly more likely to experience a thrombotic event (p=.019, events occurring a range 1 day to 47 months after co-prescription). No significant difference in thrombotic risk was seen based on active cancer treatment, age, sex, indication for anticoagulation, or apixaban dose. Seizures and thrombosis are common complications of cancer that generally necessitate pharmacotherapy. In our study of patients treated with concurrent apixaban and levetiracetam, we found an elevated thrombotic event occurrence compared with the report rate of thrombotic events on apixaban alone. This data warrants further investigation into the potential clinical significance of apixaban and levetiracetam interactions.