Characterization of an andexanet alfa administration protocol guided by drug-specific quantitative anti-Xa assays.

Following FDA approval in 2018, consensus guidelines recommend andexanet alfa as first-line therapy for the management of life-threatening or uncontrollable bleeding in patients taking oral factor Xa (FXa) inhibitors. Dosing is based on the specific FXa inhibitor and dose, and the time elapsed since the patient's last administration of the medication. Additionally, at our institution, anti-FXa screens and drug-specific assays are obtained to guide subsequent dosing based on institution protocol. The objective of this study was to evaluate andexanet alfa utilization based on anti-Xa and FXa-inhibitor-specific assays and assess associated outcomes. This was a retrospective, single-center study aimed to describe the use of anti-FXa and specific direct oral anticoagulant assays to guide the utilization and administration of andexanet alfa. Secondary endpoints evaluated included thrombotic events during index hospitalization, hospital length of stay, hospital mortality, and discharge disposition. Overall, most patients were prescribed apixaban for atrial fibrillation and received andexanet alfa for reversal of intracranial hemorrhage in the emergency department. In general, DOAC-specific assays were concordant with last known times; however, there appears to be minimal correlation with DOAC-specific assay levels and survival. There were 9 thrombotic events (8.7%) in 8 patients. In this cohort, collection of an anti-FXa assay screen was a practical strategy to guide reversal with andexanet alfa; however, the addition of DOAC-specific assay levels may not enhance clinical utility.

Evaluation of phenobarbital dosing strategies for hospitalized patients with alcohol withdrawal syndrome.

OBJECTIVE: Alcohol remains the fourth­leading preventable cause of death in the U.S. The objective of this study was to compare the incidence of phenobarbital (PHB)-resistant withdrawal and determine risk factors for PHB-resistant alcohol withdrawal syndrome (AWS). METHODS: This retrospective cohort study included adults admitted to an academic center with AWS who received PHB as part of an institution-specific treatment protocol. The primary outcome was incidence of AWS resistant to initial protocolized PHB load across two cohorts (standard-dose, 10 mg/kg vs. low-dose, 6 mg/kg). RESULTS: Among 176 included patients, there was no difference in the incidence of PHB-resistant AWS based on initial PHB load [low-dose load, 21 (18.3%) vs. standard-dose load, 12 (19.7%), p = 0.82]. There were also no differences in observed PHB-related ADEs between the groups. Total benzodiazepine dose received (mg) in the 24 h prior to initial PHB load was the only risk factor significantly associated with AWS resistant to initial protocolized PHB load [adjusted OR 1.79 (95% CI 1.24, 2.60)]. PHB-resistant withdrawal occurred in 33 (18.8%) patients with a median cumulative PHB dose of approximately 20 mg/kg during hospitalization. CONCLUSION(S): There were no differences in the incidence of PHB-resistant AWS or PHB-related ADEs based on initial PHB loading dose.