title: Absence of a clinically relevant interaction between etanercept and digoxin.
abstract: Etanercept, a soluble recombinant human tumor necrosis factor receptor (TNFr), is effective and well tolerated in the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis. The primary objective of this study was to investigate the potential pharmacokinetic and pharmacodynamic interaction between digoxin and etanercept at steady state. In a crossover, open-label, nonrandomized, 3-period study, 12 healthy male subjects received loading oral doses of digoxin 0.5 mg every 12 hours on day 1 and 0.25 mg every 12 hours on day 2, followed by a daily maintenance dose of 0.25 mg for a total of 27 days. Etanercept was administered as a twice-weekly 25-mg subcutaneous dose beginning on day 9 and continuing up to day 37 for a total of 9 doses. All ratios of maximum plasma concentration (C(max)) and area under the plasma concentration versus time curve (AUC) for pharmacokinetics of digoxin fell within the confidence interval of 0.8 to 1.25. Although not considered clinically relevant, the mean C(max) and AUC of etanercept were 4.2% and 12.5% lower, respectively, when etanercept was given with digoxin than when administered alone. There were no clinically relevant changes in the electrocardiogram (ECG) parameters, and adverse events did not increase when both drugs were combined. In conclusion, there is no clinically relevant interaction between etanercept and digoxin, and both drugs can be safely coadministered without the need for a dosage adjustment.
authors.affiliation: Clinical Pharmacology, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA.
authors.forename: Honghui
authors.initials: H
authors.lastname: Zhou
authors.forename: Virginia
authors.initials: V
authors.lastname: Parks
authors.forename: Alain
authors.initials: A
authors.lastname: Patat
authors.forename: Franck
authors.initials: F
authors.lastname: Le Coz
authors.forename: Donna
authors.initials: D
authors.lastname: Simcoe
authors.forename: Joan
authors.initials: J
authors.lastname: Korth-Bradley
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004077:Digoxin / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004562:Electrocardiography; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000378:metabolism*; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D002316:Cardiotonic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D004077:Digoxin; D000068800:Etanercept