Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
Information source: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Oral Anticoagulation; Deep Venous Thrombosis; Atrial Fibrillation; Pulmonary Embolism
Intervention: Firstly : Amoxicillin-Clavulanic acid and secondly : Placebo (Drug); Firstly : Placebo and secondly : Amoxicillin-Clavulanic acid (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Assistance Publique - Hôpitaux de Paris Official(s) and/or principal investigator(s): Stephane MD MOULY, MD, PhD, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris
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.
Clinical Details
Official title: Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: INR at day one and seven (delta Day7-Day1)
Secondary outcome: % of patients with an INR>3.5 during each study period mean INR during each study period effect of VKORC1 genetic polymorphism trough blood concentrations of S and R warfarin at day1 and day7 (delta) during each study period
Detailed 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
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
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
Locations and Contacts
Hopital Lariboisière - Service de médecine interne, Paris 75475, France
Additional Information
Starting date: March 2008
Last updated: July 9, 2010
|