INR Decreases When Antibiotic Added to Vitamin K Antagonists

One major concern with vitamin K antagonists (VKAs) is their potential for drug interactions that prompt insufficient or excessive anticoagulation.

For instance, case reports have indicated that the common penicillin antibiotic dicloxacillin can lower the anticoagulant effect of the popular VKA warfarin.

To put this theory to the test, researchers studied the potential drug-drug interaction between dicloxacillin and the VKAs warfarin and phenprocoumon.

Using an anticoagulant database of 7400 VKA-treated patients, they identified those who filled a prescription for dicloxacillin while receiving warfarin therapy between March 1998 and November 2012.

Patients were excluded if their international normalized ratio (INR) was not recorded in the anticoagulant database within 2 to 4 weeks of dicloxacillin exposure. In total, 236 patients met inclusion criteria.

Before dicloxacillin was introduced, the average INR level in patients taking warfarin was 2.58. This dropped to 1.97 within 2 to 4 weeks of dicloxacillin treatment, when 61% of patients had subtherapeutic INR levels.

Among 64 patients taking phenprocoumon, mean INR was 2.61 before dicloxacillin exposure, and it dropped to 2.30 after exposure, when 41% of patients had subtherapeutic INR.

“A biologically plausible rationale for the finding is through dicloxacillin activation of pregnane X receptor, resulting in induction of CYP3A4 and probably CYP2C9, which catalyze the metabolism of warfarin,” the authors postulated.

The researchers conceded that their study had some limitations, including the fact that dicloxacillin can be used to treat impetigo, an infection that has been reported to increase INR.

Nevertheless, they cautioned, “Physicians should be aware that dicloxacillin treatment may cause a significant decrease in INR levels among patients taking VKAs.”

Their study appeared as a research letter in JAMA.