A recent study published in Annals of Internal Medicine on February 24, 2026, reveals important information regarding a drug-drug interaction (DDI) that results in increased bleeding risk associated with the combination of diltiazem with direct oral anticoagulants (DOACs), specifically apixaban and rivaroxaban, in patients with atrial fibrillation (AF).
Diltiazem is commonly prescribed for ventricular rate control in AF, while apixaban and rivaroxaban are widely used factor Xa inhibitors for stroke prevention. The pharmacologic concern is well established: diltiazem inhibits both CYP3A4 and P-glycoprotein (P-gp) pathways, which are significantly involved in the metabolic pathways of these anticoagulants. Apixaban and rivaroxaban product labeling both caution about the concurrent use with strong inhibitors of CYP3A4 and P-gp. As a result, concomitant use may increase plasma concentrations of these DOACs resulting in an associated increased bleeding risk.
In this retrospective cohort study, investigators analyzed approximately 46,000 U.S. patients with commercial health care coverage who had AF and were on DOAC therapy (either apixaban or rivaroxaban) together with diltiazem or metoprolol. After propensity-score matching, 23,000 patients remained in each treatment group (diltiazem or metoprolol). Compared with metoprolol, diltiazem was associated with a significantly higher rate of serious bleeding events requiring hospitalization. The absolute rate difference was 5.4 additional bleeding events per 1,000 person-years.
Importantly, the interaction appeared dose dependent. Patients receiving diltiazem doses greater than 120 mg/day experienced substantially higher bleeding risk than those receiving lower doses. At 12 months, the absolute excess bleeding risk associated with diltiazem versus metoprolol was approximately 0.48 percentage points (6 months equated to 0.31). Stroke and systemic embolism rates were not statistically different between the diltiazem and metoprolol groups, suggesting that the increased harm was not offset by improved thromboembolic protection.
There are certainly situations where diltiazem may be clinically appropriate over metoprolol in a patient requiring rate control for the treatment of AF. Nevertheless, for patients on DOAC therapy (particularly apixaban or rivaroxaban), metoprolol may represent a safer first-line option when clinically appropriate, especially in individuals with elevated bleeding risk, prior hemorrhage, advanced age, polypharmacy, renal impairment, or concomitant antiplatelet therapy. If diltiazem is necessary, whether due to prior intolerance or contraindications to beta-blockers, prescribers should consider using the lowest effective dose and monitor carefully for signs or symptoms of bleeding complications.
Overall, this study highlights the importance of routinely reviewing drug–drug interactions in anticoagulated patients. Although the absolute increase in bleeding risk was modest, the high prevalence of AF and widespread use of these medications make the interaction clinically meaningful when making therapeutic decisions that are meant to balance both therapeutic efficacy with safety.
The United States Food and Drug Administration (FDA) announced an important recall of True Metrix glucometers on April 28, 2026.
The Class I (most serious) recall involves all True Metrix, True Metrix Air and True Metrix Go personal use glucometers, as well as True Metrix Pro professional glucometers. (True Metrix brand products are often cobranded and sold under various store names as well). At the time of the recall announcement, 114 injuries and 1 death have resulted from the identified problem.
The recall stems from a problem with a software design of the E-5 error code, along with the user instructions associated with the E-5 error code in the owner’s booklet.
If a user encounters an E-5 error, and the error code is misinterpreted as a test strip error when, in fact, the error indicates a blood glucose in excess of 600 mg/dL, they may delay treatment. An E-5 error may also prompt the user to initiate treatment measures to reduce blood glucose when, in fact, the glucose value is low or normal. In either event, a delay or improper treatment could lead to serious consequences, including dehydration, altered mental status, loss of consciousness or fatality, as evidenced by the 114 injuries and one death mentioned above.
Patients are advised to use other means to test blood glucose until corrected meters are made available, especially highest-risk users (patients using intensive insulin therapy, sulfonylurea therapy, or frequent high- or low-glucose events). However, all users are instructed to continue to use their True Metrix meter until an alternative testing method has been secured. In the meantime, users should be aware that an E-5 error code could either mean a dangerously high blood sugar value -OR- a simple test strip error. If an E-5 error is encountered, patients should reach out to their health care provider for triage immediately.
A downloadable full list of affected devices is available here, bearing in mind that True Metrix meters are often sold as store-branded meters.
Update 1: Name Change/Dose change for Semaglutide Tablets
Update 2: A new GLP-1RA oral: orforglipron
How it compares to semaglutide oral:
Clinical Pharmacy Practitioner in Primary Care
Mike Grunske, PharmD, BCPS
Mike Grunske is a Board-Certified Pharmacotherapy Specialist (BCPS). Mike transitioned his practice to the Clement Zablocki VA Medical Center where he has since practiced in the Primary Care Clinics as a Clinical Pharmacist Practioner. Within this role, his practice involves direct care and management of patients’ medication regimens. He has worked as an active preceptor for both pharmacy students and residents throughout his entire career. Mike is also Past-President and former Foundation Chair of the Pharmacy Society of Wisconsin (PSW).
Mike is married to a fellow PharmAid contributor (Vanessa Grunske). Together they have a teenage daughter and son. He enjoys traveling with his family, attending his kid’s cheer, baseball, and basketball events, and spending any available leftover time running and hunting.
Pharmacist at Advocate Aurora Health
Vanessa Grunske, PharmD, BCACP
Vanessa practices with Advocate Aurora Health in Milwaukee, where she sees patients at Aurora Sinai Medication Management Clinic and maintains a dispensing practice at St. Luke’s Medical Center. Board-certified in ambulatory care pharmacotherapy, her practice interests include diabetes, hypertension, smoking cessation, geriatrics, improving health literacy, and medication adherence. She particularly enjoys and spends a good share of her work hours teaching and mentoring pharmacy students, family medicine residents and pharmacy residents.
She and her husband, Mike, live in the Milwaukee area with their two teenage children. In her free time, she enjoys cooking, baking, visiting our national parks with her family or relaxing on a beautiful Caribbean beach.
Professor at Concordia University Wisconsin School of Pharmacy
Beth Buckley, PharmD, CDCES
Beth Buckley, PharmD, CDCES (Certified Diabetes Care and Education Specialist), is a Professor of Pharmacy Practice at the Concordia University Wisconsin School of Pharmacy, where she has a teaching role within all years of the curriculum with a focus on Applied Patient Care Skills Lab, Diabetes Pharmacotherapy, and electives in the areas of diabetes and wellness. Her current role is ambulatory care pharmacist where she works with a Collaborative Practice Agreement to provide chronic disease state management within a primary care clinic.
When not working, she enjoys reading, gardening, traveling with her husband, volunteering within the community, and active fun: hiking, biking, dog walking, practicing yoga, mindfulness, and living with intention and gratitude.
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