Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid

Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid

Several case reports indicate that the use of the antibiotic combination amoxicillin and clavulanic acid (AM-CLAVAC) can interact with warfarin pharmacodynamics. However, fever per se might also be responsible of these warfarin overdose reports, as well as the use of high dose paracetamol.

The aim of the present study is to determine if AM-CLAVAC can increase the pharmacodynamics of warfarin among patients at steady state Double blinded cross over controlled study vs placebo performed in 12 evaluable patients treated with warfarin with an INR target 2 to 3 and a stable INR and a stable dose.

Double blinded cross over controlled study vs placebo performed in 12 evaluable patients treated with warfarin with an INR target 2 to 3 and a stable INR and a stable dose

One period : seven consecutive days of amoxicillin(2g twice daily)- clavulanic acid (125 mg twice daily) association Wash out period of at least 4 weak with the return to a stable INR and warfarin dose One period : seven consecutive days of placebo twice daily

Main outcome INR delta Day7-Day

Inclusion Criteria:

• patients treated with warfarin (target INR 2 to 3)
• stable anticoagulation (3 consecutive INR in the target)
• stable dose
• no infection
• normal CRP
• age >18 years
• normal transaminase levels

Exclusion Criteria:

• drug allergy
• penicillin allergy
• Alzheimer
• cancer
• thyroid disease
• gastro intestinal chronic disease
• frequent nausea or vomiting
• Cirrhosis
• chronic renal failure (GFR<60 ml/min)
• frequent intake of paracetamol or NSAID
• addict to drugs or alcool
• St John's wort treatment or grapefruit juice intake
• concomitant drugs (amiodarone, cimetidine, SSRI, clofibrate, fenofibrate, diltiazem, fluconazole, itraconazole, isoniazide, voriconazole, métronidazole, miconazole , omeprazole, glucocorticoids, zileuton, ritonavir, rifampicin, carbamazepine, phenytoin, phenobarbital)
• antibiotic use during the 3 last weeks
• pregnancy