DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Drug Interaction Between Paracetamol and Warfarin

Information source: Hopital Lariboisière
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Deep Venous Thrombosis; Pulmonary Embolism; Atrial Fibrillation; Stroke; Antiphospholipid Syndrome

Intervention: paracetamol (Drug); paracetamol (Drug); Placebo (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Hopital Lariboisière

Official(s) and/or principal investigator(s):
Stephane Mouly, MD, PhD, Principal Investigator, Affiliation: Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisière, Paris, France
Guy Simoneau, MD, Principal Investigator, Affiliation: Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisière, Paris, France

Summary

The objective of this study is to investigate whether paracetamol, given at therapeutic doses (2g/day and 3 g/day), may potentiate the anticoagulant effect of warfarin.

Clinical Details

Official title: Dose-dependent Drug-drug Interaction Between Paracetamol and Warfarin in Adults Receiving Long-term Oral Anticoagulants: A Randomized Controlled Trial

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Screening

Primary outcome: The mean maximum increase in INR from baseline to Day 10 (INR (max-D1))

Secondary outcome:

The mean maximum INR (INRmax)

The time to the first variation of INR observed

Day 10 - Day 1 differences in factors II, V, VII, AT-III plasma concentrations between groups.

Day 10 - Day 1 differences in paracetamol plasma concentration between groups.

Day 10 - Day 1 differences in R(-), S(-)warfarin plasma concentrations between groups.

Day 10 - Day 1 differences in Gla-type Osteocalcin (Gla-OC) and undercarboxylated Osteocalcin (Glu-OC)plasma concentrations between groups.

Relation between age and the mean maximum increase in INR from baseline to Day 10 (INR (max-D1)

Detailed description: Paracetamol is recommended as a first-line analgesic and antipyretic therapy in patients receiving short- and long-term oral anticoagulation, especially elderly patient. However,Increased INR was previously observed in patients treated with warfarin and paracetamol given at the maximum recommended dose (4g/day). To date, the mechanism of this interaction has not been determined. A recent in vitro study suggested that the toxic metabolite N-acetyl-para-benzoquinoneimine (NAPQI) appeared to interfere with vitamin K-dependent γ-carboxylase (VKD-carb) and vitamin K epoxide reductase (VKOR) activites12. The question remaining to be dealt with is whether this in vitro observation can explain the in vivo paracetamol-warfarin interaction. We aim to evaluate the effect of paracetamol at the most widely used doses 2 and 3g/day on INR in stable patients treated with warfarin in a double blind randomized placebo-controlled trial and to identify the mechanism involved in this interaction in vivo.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients treated with warfarin (target INR 2 to 3) stable anticoagulation at 2 to 9

mg for more than 30 days

- Aged 18 years or older

- Laboratory values (hemoglobin, blood cell counts, albumin, blood ionogram,

complementary hemostasis parameters and aspartate, alanine transaminases (AST and ALT))remained within normal limits Exclusion Criteria:

- Any treatment change within 7 days before enrollment

- Any paracetamol intake within the last 14 days

- Drug allergy Concomitant drug ( 5-fluorouracile, acetylsalicylic acid, non steroidal

anti-inflammatory drugs, chloramphenicol, diflunisal, miconazole)

- St John's wort treatment

- Pregnancy

Locations and Contacts

Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboière, Paris 75010, France
Additional Information

Starting date: March 2007
Last updated: April 13, 2010

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017