Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid

• Status: Completed
• Trial end date: 2010-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Clavulanic Acid; Clavulanic Acids; Warfarin

Criteria

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