Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid (INWARA)

Assistance Publique - Hôpitaux de Paris

Status and phase

Completed

Phase 4

Conditions

Pulmonary Embolism

Atrial Fibrillation

Deep Venous Thrombosis

Oral Anticoagulation

Treatments

Drug: Firstly : Amoxicillin-Clavulanic acid and secondly : Placebo

Drug: Firstly : Placebo and secondly : Amoxicillin-Clavulanic acid

Study type

Interventional

Funder types

Other

Identifiers

NCT00603317

P051056

Details and patient eligibility

About

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.

Full description

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

Enrollment

13 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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