The antibiotic dicloxacillin appears to markedly decrease INR levels in patients taking warfarin, reducing the mean INR to subtherapeutic ranges in the majority who take both drugs concomitantly, according to a research letter to the editor published online July 20 in JAMA.
Adverse interactions between warfarin and other drugs are often suspected, but solid data are lacking. Case reports have suggested that the commonly used antibiotic dicloxacillin reduces warfarin’s anticoagulant effects, but no studies have examined the issue, said Anton Pottegård, Ph.D., of the department of clinical pharmacology, University of Southern Denmark, Odense, and his associates (JAMA 2015;314:296-7).
To further investigate that possibility, the investigators analyzed information in an anticoagulant database covering 7,400 patients treated by three outpatient clinics and 50 general practitioners during a 15-year period. They focused on weekly INR levels recorded for 236 patients (median age, 68 years), most of whom took warfarin because of atrial fibrillation or heart valve replacement.
The mean INR level before dicloxacillin exposure was 2.59, compared with 1.97 after dicloxacillin exposure (P < .001). A total of 144 patients (61%) had subtherapeutic INR levels (< 2.0) during the 2-4 weeks following a course of dicloxacillin, Dr. Pottegård and his associates said.
A similar but less drastic decrease was observed among the 64 patients taking a different anticoagulant, phenprocoumon, who were given dicloxacillin. Mean INR levels dropped from 2.61 before exposure to 2.30 afterward (P = .003), and 41% of the group had subtherapeutic INR levels after taking the antibiotic.
No sponsor was reported for this study. Dr. Pottegård and his associates reported having no relevant financial disclosures.