Evaluating pharmacokinetic drug-drug interactions of direct oral anticoagulants in patients with renal dysfunction.

Introduction: Drug transporters, metabolic enzymes, and renal clearance play significant roles in the pharmacokinetics of direct oral anticoagulants (DOACs). Recommendations for DOAC drug-drug interactions (DDIs) by the product labeling are limited to selected CYP3A4 and P-glycoprotein inhibitors and lack considerations for concomitant renal dysfunction.

Areas Covered: This review focuses on: 1) current recommendations for the management of pharmacokinetic DOAC DDIs and the evidence used to support them; 2) alterations in DOAC exposure in the setting of concomitant DDIs and mild, moderate, and severe renal impairment; 3) clinical outcomes associated with this combination; and 4) expert recommendations for the management of pharmacokinetic DOAC DDIs.

Effect of Replacing Vendor QTc Alerts with a Custom QTc Risk Alert in Inpatients.

Objective: The aim of the study is to implement a customized QTc interval clinical decision support (CDS) alert strategy in our electronic health record for hospitalized patients and aimed at providers with the following objectives: minimize QTc prolongation, minimize exposure to QTc prolonging medications, and decrease overall QTc-related alerts. A strategy that was based on the validated QTc risk scoring tool and replacing medication knowledge vendor alerts with custom QTc prolongation alerts was implemented.

Methods: This is a retrospective quasi-experimental study with a pre-intervention period (August 2019 to October 2019) and post-intervention period (December 2019 to February 2020).

Standard Versus Higher Intensity Anticoagulation for Patients With Mechanical Aortic Valve Replacement and Additional Risk Factors for Thromboembolism.

Current guidelines recommend targeting an international normalized ratio (INR) of 2.5 to 3.5 for patients with mechanical aortic valve replacement (AVR) and additional risk factors for thromboembolic events.

Anti-factor IIa (FIIa) heparin assay for patients on direct factor Xa (FXa) inhibitors.

Background: Direct factor Xa (FXa) inhibitors are increasingly prescribed for outpatients, and those transitioning to unfractionated heparin (UFH) for hospital admission are monitored via an anti-FXa assay. Because of assay interference, UFH results would often be critically elevated, confounding dosing.

Objectives: An anti-factor IIa (FIIa) UFH assay was evaluated for clinical use.

The real world use of combined P-glycoprotein and moderate CYP3A4 inhibitors with rivaroxaban or apixaban increases bleeding.

The use of direct oral anticoagulants for stroke prevention in atrial fibrillation continues to rise. Certain populations may be at higher risk for increased drug exposure and adverse events. Pharmacokinetic studies suggest increased exposure of rivaroxaban and apixaban with combined P-gp and moderate CYP3A4 inhibitors but the clinical relevance of this is unknown.

Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

Background: Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC.

Impact of a Guideline for the Management of Antimicrobial/Warfarin Interactions in the Inpatient Setting and Across Transition of Care.

Background: Drug-drug interactions (DDIs) with warfarin and antimicrobial agents are a common cause of international normalized ratio (INR) instability, which can affect the risk for bleeding and thrombotic events.

Objective: The purpose of this study was to assess the impact of a comprehensive guideline for the management of warfarin-antimicrobial DDIs across transitions of care. The guideline emphasizes improving identification of significant antimicrobial-warfarin DDIs during hospitalization, empirical warfarin dose modification based on DDI and baseline INR, patient education, documentation of the DDI, communication with outpatient providers regarding the DDI and anticipated antimicrobial stop date, and warfarin dose adjustment on discontinuation of antimicrobial.

Effects of Total Dose Infusion of Iron Intravenously in Patients With Acute Heart Failure and Anemia (Hemoglobin < 13 g/dl).

Iron deficiency is common in heart failure (HF), and intravenous (IV) iron therapy has been associated with improved clinical status in ambulatory patients with HF. There are limited data to support the safety and efficacy of IV iron administration in patients with acute HF. This was a retrospective cohort study of patients admitted to the University of Michigan Health System for HF with low iron studies during admission.