Ischemic stroke due to possible interaction of rivaroxaban with primidone in a patient with atrial fibrillation

Drug-drug interactions between direct oral anticoagulants and anticonvulsants and clinical outcomes: A systematic review

“…In total, 874 articles were retrieved from the search, and from this group, we identified 15 relevant studies, including 4 congress abstracts [ [10] , [11] , [12] , [13] ], 3 case reports [ [14] , [15] , [16] ], 2 letters to the editor [ 17 , 18 ], 5 retrospective cohorts [ 6 , [19] , [20] , [21] , [22] ], and one prospective cohort study [ 23 ] ( Table ).…”

“… Robinson [ 17 ] 2021 Letter to the editor 1 Rivaroxaban Oxcarbazepine Gabapentin Topiramate Pulmonary embolism PE in a patient with heterozygous prothrombin gene mutation, a history of PE, schizophrenia, psychosis, and bipolar disorder. Sáez-Torres de Vicente [ 18 ] 2021 Letter to the editor 1 Rivaroxaban Primidone Stroke Stroke in a patient with AF on treatment with primidone and rivaroxaban. Candeloro [ 20 ] 2022 Retrospective cohort 32 Dabigatran Rivaroxaban Apixaban Edoxaban Carbamazepine Phenytoin Thrombotic event Major bleeding All-cause mortality Patients with AF or VTE co-treated with a DOAC and carbamazepine or phenytoin had 4.4 per 100 person-year incidence of thromboembolism, 1.5 (95% CI, 1.2-1.9) per 100 person-year major bleeding, and 1.5 (95% CI, 1.2-1.9) per 100 person-year all-cause mortality.…”

“…The patient developed a new pulmonary embolism with undetectable serum levels of rivaroxaban [ 17 ]. In another letter to the editor, a case of an 80-year-old woman with AF on treatment with rivaroxaban 20 mg and primidone who developed an ischemic stroke was reported [ 18 ]. In an observational study, the co-prescription of rivaroxaban and phenytoin was associated with at least one thrombotic event among 4924 patients (RR 2.39; 95% CI, 1.33-3.29) [ 19 ].…”

“…These data are subject to publication bias with cases associated with unfavorable outcomes more likely to be reported than cases with no apparent impact on these outcomes. Moreover, these data were limited by multiple confounders including concomitant thrombophilias, other thrombotic risk factors [ [13] , [14] , [15] , 17 , 18 ], and incomplete information about DOAC or AE drug dose and adherence. Three of the retrospective cohorts we analyzed were based on large numbers of patients from national or claims-based databases [ 6 , 19 , 22 ].…”