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 Dosing Regimens of Vancomycin and Aminoglycosides in Pediatric Patients on Continuous Renal Replacement Therapy.

OBJECTIVE: To determine the optimal empiric dosing regimen to achieve therapeutic serum concentrations of vancomycin and aminoglycosides in pediatric patients who are receiving continuous renal replacement therapy (CRRT). METHODS: This retrospective study investigated pediatric patients (<18 years old) who received at least one dose of an aminoglycoside and/or vancomycin while on CRRT and who had at least one serum concentration assessed during the study period. Rates of culture clearance and discontinuation of renal replacement therapy, pharmacokinetic variables (i.e., volume of distribution [Vd], half-life [t½], rate of elimination [ke]), and correlations between patient's age and weight in regard to the empiric dosing regimen were evaluated. RESULTS: Forty-three patients were included in this study. The median dose required to reach therapeutic serum concentrations for vancomycin was 17.6 mg/kg (12.8-20.4 mg/kg) every 12 hours (6-30 hours) in continuous venovenous hemodialysis (CVVHD) patients and 16.3 mg/kg (13.9-21.4 mg/kg) every 12 hours (6-24 hours) in continuous venovenous hemodiafiltration (CVVHDF) patients. The median dose for aminoglycosides was unable to be determined. In CVVHD patients, the median vancomycin ke was 0.04 hr-1, t½ was 18 hours, and Vd was 1.6 L/kg. In CVVHDF patients, the median vancomycin ke was 0.05 hr-1, t½ was 14 hours, and Vd was 0.6 L/kg. No correlation was found between age and weight with regard to effective dosing regimen. CONCLUSIONS: To achieve therapeutic trough concentrations in pediatric patients on CRRT, vancomycin should be dosed at approximately 17.5 mg/kg administered every 12 hours.

Andexanet alfa and four-factor prothrombin complex concentrate for reversal of apixaban and rivaroxaban in patients diagnosed with intracranial hemorrhage.

Limited data exists regarding the clinical outcomes of andexanet alfa and four factor prothrombin complex concentrate (4F-PCC) for reversal of apixaban or rivaroxaban in the setting of intracranial hemorrhage (ICH). The objective of this study was to evaluate clinical outcomes of 4F-PCC and andexanet alfa for reversal of ICH associated with oral factor Xa inhibitors. This was a retrospective, single-center, case series evaluating hemostatic efficacy of patients receiving andexanet alfa) or 4F-PCC for reversal of apixaban or rivaroxaban after ICH. Secondary endpoints included in-hospital mortality, thrombotic complications, timing of reversal agents, intensive care unit and hospital length of stay, patient disposition, and 30-day readmission rate. During the study period, 21 patients received andexanet alfa and 35 received 4F-PCC. Hemostatic efficacy occurred in 64.7% of patients receiving andexanet alfa and 54.8% of receiving 4F-PCC. Thirty-day all-cause mortality was 45.2% for 4F-PCC and 30% for andexanet alfa. Thrombotic events were higher with 4F-PCC (31.4%) compared to andexanet alfa (14.3%). Median time from presentation to administration of reversal agent was 2.67 [1.75-4.13] hours with andexanet alfa and 1.73 [1.21-3.55] hours with 4F-PCC. Discharge to skilled nursing facilities and 30-day readmission were similar between groups. In this cohort, reversal with andexanet alfa and 4F-PCC differed in terms ofhemostatic efficacy and thrombotic events after ICH in patients anticoagulated with apixaban or rivaroxaban.

Accuracy of and prescriber perceptions related to documenting antibiotic indications during order entry at an academic medical center.

PURPOSE: To assess the accuracy of antibiotic indication documentation provided during order entry and prescriber perceptions of the requirement to specify indications. METHODS: Patients who received 1 of 6 selected antibiotics from May 1 through June 30, 2017, were identified. Records of 30 randomly selected patients who received each study antibiotic were retrospectively reviewed. The primary endpoint was indication accuracy, defined as agreement of the indication entered during order entry with that documented in progress notes at the time of order entry. Secondary endpoints included correlation of entered indication and final diagnosis for empiric antibiotics. A brief survey was emailed to prescribers to assess the burden and perceptions of requiring an indication during order entry. RESULTS: Four thousand five hundred twenty-four patients received 1 or more doses of a study antibiotic. For the 180 patients selected for evaluation, 89.4% of indications were accurate. Indications for antibiotics ordered for prophylaxis were more likely to be inaccurate than those for empiric or definitive antibiotics (accuracy rates of 46%, 94%, and 92%, respectively, p < 0.05). For empiric antibiotics, 78.5% of indications documented at order entry matched the final diagnosis. Two hundred fifty-four of 863 prescribers (29%) responded to the survey request. Most respondents felt that documenting the indication took no more than 20 seconds, was a "minor nuisance" or "occasionally burdensome," and had no impact on their consideration of antibiotic appropriateness. CONCLUSION: With the exception of prophylaxis, the indications documented during order entry were sufficiently accurate to assist antimicrobial stewardship efforts. Although indication documentation was perceived as a minor burden, surveyed prescribers indicated it had only a minimal beneficial effect on antibiotic prescribing.

Reversal agents for oral anticoagulants.

For more than half a century, warfarin, a vitamin K antagonist, has been the anticoagulant of choice. However, direct oral anticoagulants are rapidly gaining in popularity, which poses the need for efficacious reversal agents. This review article summarizes the strategies and agents used to reverse oral anticoagulants.