Drug Interaction Between Paracetamol and Warfarin (INPAWA2)

Hopital Lariboisière

Status and phase: Completed; Phase 4

Conditions: Pulmonary Embolism; Atrial Fibrillation; Antiphospholipid Syndrome; Deep Venous Thrombosis; Stroke

Treatments: Drug: paracetamol; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01104337

INPAWA2-URT

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

45 participants in 3 patient groups, including a placebo group

Paracetamol 2g/d

Experimental group

Description:

18 patients on stable warfarin therapy received a 10-day regimen of paracetamol 2g/d

Treatment:

Drug: paracetamol

Drug: paracetamol

Paracetamol 3g/d

Experimental group

Description:

18 patients on stable warfarin therapy received a 10-day regimen of paracetamol 3g/d

Treatment:

Drug: paracetamol

Drug: paracetamol

Placebo

Placebo Comparator group

Description:

9 patients on stable warfarin therapy received a 10-day regimen of placebo

Treatment:

Drug: Placebo