Absence of interaction of fondaparinux sodium with aspirin and piroxicam in healthy male volunteers

Patients undergoing major orthopaedic surgery who are being treated with fondaparinux sodium for prevention of venous thromboembolism may be receiving treatment for coronary artery disease or chronic inflammatory disease of the joints or arthritis. Two separate studies assessed any possible interact...

Full description

Saved in:
Bibliographic Details
Published in:Clinical pharmacokinetics 2002, Vol.41 Suppl 2 (Supplement 2), p.31-37
Main Authors: Ollier, Céline, Faaij, Richard A, Santoni, Alix, Duvauchelle, Thierry, van Haard, Paul M M, Schoemaker, Rik C, Cohen, Adam F, de Greef, Rik, Burggraaf, Jacobus
Format: Article
Language:English
Subjects:
Adult
Aspirin - pharmacology
Bleeding Time
Cross-Over Studies
Double-Blind Method
Drug Interactions
Fibrinolytic Agents - blood
Fibrinolytic Agents - pharmacokinetics
Fibrinolytic Agents - pharmacology
Humans
Male
Middle Aged
Partial Thromboplastin Time
Piroxicam - pharmacology
Platelet Aggregation Inhibitors - blood
Platelet Aggregation Inhibitors - pharmacokinetics
Platelet Aggregation Inhibitors - pharmacology
Polysaccharides - blood
Polysaccharides - pharmacokinetics
Polysaccharides - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Patients undergoing major orthopaedic surgery who are being treated with fondaparinux sodium for prevention of venous thromboembolism may be receiving treatment for coronary artery disease or chronic inflammatory disease of the joints or arthritis. Two separate studies assessed any possible interaction between fondaparinux sodium at steady state and aspirin (acetylsalicylic acid) or piroxicam in healthy volunteers. In the first study a single dose of aspirin 975mg was assessed initially, followed by single doses of aspirin or placebo on the fourth day of an 8-day regimen of subcutaneous fondaparinux sodium (10mg once daily). The second study was a three-way crossover, double-blind, randomised study which investigated fondaparinux sodium 10mg + placebo, fondaparinux sodium 10mg + piroxicam 20mg, or placebo + piroxicam 20mg. Both studies obtained plasma concentration-time profiles of fondaparinux sodium administered alone and with aspirin or piroxicam. Noncompartmental parameters - peak concentration, trough concentration, time to reach peak concentration, and area under the concentration-time curve - were obtained. Both studies measured the pharmacodynamic parameters bleeding time and activated partial thromboplastin time (aPTT). Safety was monitored. Neither aspirin nor piroxicam influenced the pharmacokinetics of fondaparinux sodium at steady state. Two hours after administration, prolongation of bleeding time with aspirin alone or with aspirin plus fondaparinux sodium was significantly greater than with fondaparinux sodium alone (p = 0.003 and p = 0.004, respectively). No significant differences were observed between aspirin alone or aspirin + fondaparinux sodium in effect on bleeding time. A small decrease in collagen-induced platelet aggregation was observed after administration of piroxicam alone or piroxicam + fondaparinux sodium. A small effect on aPTT was observed; it was similar for fondaparinux sodium whether administered alone or in combination with either aspirin or piroxicam. No serious adverse events were reported.
ISSN:0312-5963
1179-1926
DOI:10.2165/00003088-200241002-00005