RESUMEN
Background: Previous studies identified a rapid decrease in valproate serum concentrations when coadministered with a carbapenem; however, the specific consequences and subsequent therapy adjustments are not well described. We aimed to investigate the clinical and therapeutic implications of the carbapenem-valproate drug-drug interaction. Methods: This retrospective analysis included data from 2 large academic medical centers during January 2017 to June 2022. The primary outcome was incidence of seizures or behavioral events stratified by valproate indication. All adult patient encounters with concomitant administration of any carbapenem antimicrobial and valproate were included. Patients without prolonged exposure to valproate prior to hospitalization, without valproate levels pre- and post-carbapenem administration, with an admitting diagnosis of seizure, with exposure to other agents that decrease valproate concentrations, or who had a seizure during the hospitalization prior to carbapenem exposure were excluded. Results: Two hundred fifty-eight episodes of concomitant use among 78 unique adult patients were included. Valproate was used for seizure control in 41 patients (52.6%) and for mood-related disorders in 37 (47.4%). In those prescribed valproate for its antiepileptic properties, seizures occurred following carbapenem administration in 46.3% of encounters. In those taking valproate for mood-related disorders, 50.8% met the primary endpoint of behavioral disturbance. Conclusions: Our study demonstrates significant clinical implications of the carbapenem-valproate interaction. Clinicians should be aware of this interaction and consider alternative antimicrobial and/or antiepileptic agents whenever possible. Adding or increasing doses of antiepileptic agents and/or consultation with a neurologist prior to concomitant use should be considered when this combination cannot be avoided.
RESUMEN
ABSTRACT: Drug-specific anti-Xa concentrations can be used to assess the presence of drug effects; however, there is inadequate guidance for clinicians on the interpretation and clinical application of these results. The purpose of this study is to review patients' first apixaban and rivaroxaban anti-Xa concentrations to identify indications for monitoring and common therapeutic interventions made based on the results. In addition, we compared bleeding and thrombotic outcomes between the obesity group body mass index ≥40 kg/m 2 and the standard group body mass index 25-39.9 kg/m 2 . A retrospective analysis was conducted at a large academic medical center from January 1, 2020, to December 31, 2020. Primary outcomes were indications for anti-Xa concentrations and interventions on results. A total of 180 patients were included in the analysis, with 119 patients (66%) in the apixaban group and 61 patients (34%) in the rivaroxaban group. The most common indications for anti-Xa concentrations were extreme body weight (23%) and concern for bleeding (22%). About half of the anti-Xa concentrations resulted in therapy changes including holding for procedure, switching to heparin or enoxaparin, holding for an elevated anti-Xa concentration or concern for bleeding, adjusting direct-acting oral anticoagulant dose, or switching to an alternative oral anticoagulant. There were no differences in bleeding complications (5% [2] vs. 16% [14], P = 0.11) or thrombotic complications (8% [3] vs. 9% [8], P = 0.85) between the obesity group and the standard group. Despite the lack of validation of therapeutic ranges for anti-Xa concentrations, this study showed clinical situations where anti-Xa concentration monitoring can be of value.
