Amoxicillin/clavulanic acid‐warfarin drug interaction: a randomized controlled trial

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Increased INR was previously observed in patients treated with warfarin and amoxicillin/clavulanic acid (amoxiclav) combination. To date, no prospective study has yet evaluated the effect of amoxiclav on INR in patients on warfarin therapy and consequently, there are no clear-cut conclusions or clear recommendations for clinicians. WHAT THIS PAPER ADDS• We provided the first systematic prospective evaluation of the interaction between amoxiclav and warfarin and found that amoxiclav did not modify INR in patients treated with stable warfarin therapy in the absence of any infectious or inflammatory syndrome, suggesting that the previously observed INR increase in these patients may not be attributable to a drug-drug interaction. AIMSTo investigate whether an interaction exists between amoxicillin/clavulanic acid (amoxiclav) and warfarin in patients treated with stable oral anticoagulant therapy. METHODSIn a double-blind, cross-over, placebo-controlled study, 12 patients on stable warfarin therapy, received a 7 day amoxiclav regimen or placebo. RESULTSThe mean maximum increase in INR observed was 0.22 Ϯ 0.3 with amoxiclav vs. 0.24 Ϯ 0.6 with placebo (P = 0.94). The day 7-day 1 factor II, R(-) and S(-) warfarin plasma concentrations were similar during the amoxiclav and placebo study periods (P = 0.81, P = 0.45, P = 0.75, respectively). CONCLUSIONAmoxiclav did not modify anticoagulation in patients treated with stable warfarin therapy and without infection.

Effect of single-dose extended-release oral azithromycin on anticoagulation status in warfarinized patients

“…. Several studies have shown that CYP expression and activity may be decreased in humans during infection or inflammation, resulting in lowered drug clearance, increased toxicity and altered physiological function 1,2) . The infection itself (inflammatory syndrome) may alter the warfarin metabolism or hepatic clotting factor synthesis 2,3) .…”

“…Some case reports have suggested that macrolides have the potential to enhance the anticoagulation effect of warfarin [1][2][3] . However, no prospective study has yet evaluated the effect of AZ-ER on the anticoagulation of warfarin therapy.…”

“…In daily practice, the dentist usually uses antibiotics either as prophylactic cover or in the therapeutic management of infection. Antibiotics used in dentistry also have a possible capacity to interact with warfarin, producing a clinically-significant alteration in anticoagulation status [1][2][3] .…”

Gestion péri-opératoire des patients traités par antithrombotiques en chirurgie orale. Argumentaire

“…La période postopératoire est une période critique car elle s'accompagne bien souvent d'une nouvelle prescription et/ou d'une modification des habitudes alimentaires. Un suivi clinique et/ou biologique est nécessaire en cas de prescription anti-infectieuse et/ou antalgique [23,38,52,72,79,159,171,187,208,241,268,289,291,292].…”

“…Concernant la prescription d'amoxicilline seule ou en association avec l'acide clavulanique, des données contradictoires sont rapportées dans la littérature. Des cas cliniques [38,52,79,188,268], une étude cas-témoin [241], une enquête prospective [261] [292]. Il est à rappeler qu'une infection avec les modications métaboliques qui l'accompagnent est en soit un facteur de risque de déséquilibre du traitement anticoagulant oral.…”