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Common antibiotic may decrease anticoagulant effect of warfarin
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Treatment with the antibiotic dicloxacillin significantly decreased international normalized ratio levels among patients taking vitamin K antagonists, according to the results of a registry-based study.
The use of vitamin K antagonists (VKAs) pose a potential risk for drug–drug interactions, resulting in insufficient or excessive anticoagulation; however, most alleged interactions lacked solid data. Previous reports suggested that dicloxacillin — a commonly used antibiotic — lowered the anticoagulant effect of warfarin.
Anton Pottegård, MScPharm, PhD, pharmacist and research fellow at University of Southern Denmark in Odense, and colleagues conducted a registry-based study to determine whether dicloxacillin use impeded the anticoagulant effect of warfarin in patients taking both agents.
Researchers used the anticoagulant database Thrombobase to identify Danish patients taking warfarin and included all patients taking warfarin who filled a prescription for dicloxacillin between 1998 and 2012 (n = 519).
The researchers compared the last INR measurement before dicloxacillin exposure to the first measurement within weeks 2 and 4 after dicloxacillin exposure, excluding patients who did not have a post-exposure INR measurement.
The final analysis included data from 236 patients (median age, 68 years; 61% men) who took warfarin and dicloxacillin. Eighty-nine percent of patients filled a prescription for 30 dicloxacillin tablets (range, 30-100).
Fifty-six percent of patients took warfarin for atrial fibrillation and 22% took warfarin following a heart valve replacement.
Patients had a mean INR level of 2.59 (95% CI, 2.5-2.68) prior to dicloxacillin exposure. Following exposure, INR decreased a mean 0.62 (95% CI, 0.5-0.74), which resulted in a mean INR of 1.97 (95% CI, 1.9-2.05; P < .001) in the population 2 to 4 weeks after dicloxacillin exposure.
Sixty-one percent of patients (n = 144) experienced subtherapeutic INR levels (< 2) within 2 to 4 weeks after initiating dicloxacillin treatment.
Sixty-four patients who took the VKA phenprocoumon had a mean INR level of 2.61 (95% CI, 2.46-2.76) prior to dicloxacillin exposure. Following exposure, these patients exhibited a mean decrease of 0.31 (95% CI, 0.11-0.51; P = .003). Subtherapeutic INR levels occurred in 41% of these patients.
Patients who took warfarin and phenoxymethylpenicillin (n = 539) or amoxicillin (n = 266) experienced increases in mean INR level following antibiotic exposure (phenoxymethylpenicillin, mean increase 0.1; 95% CI, 0.01-0.19; amoxicillin, 0.14; 95% CI, 0.03-0.26).
The researchers identified lack of data on the underlying infections as a study limitation. Further, they acknowledged that the study population may not be representative and generalizable to the general population.
“Physicians should be aware that dicloxacillin treatment may cause a significant decrease in INR levels among patients taking VKAs,” Pottegård and colleagues concluded. – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
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