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.

Comparative Pharmacokinetics of HD203, a Biosimilar of Etanercept, with Marketed Etanercept (Enbrel®)

“…Many pharmacokinetic studies of etanercept conducted in healthy subjects have shown that these biologic agents are well tolerated. [11,[18][19][20][21] In addition, a previous population-based pharmacokinetic study of etanercept indicated that the pharmacokinetics in rheumatoid arthritis and ankylosing spondylitis patients is similar to that in healthy volunteers. [22][23][24] Therefore, reconstituted lyophilized (25 mg mL) HD203 and Enbrel Ò can be expected to result in similar pharmacokinetics in the clinical setting.…”

Validation and application of a 96-well format solid-phase extraction and liquid chromatography–tandem mass spectrometry method for the quantitation of digoxin in human plasma

“…Almost all digoxin interaction studies have been carried out at the maintenance dose of 0.25 mg. The mean C max in these studies ranged from 1.16 to 3.70 ng/mL (Table 1) [4][5][6][7][8][9][10]. Depending on the situation, side effects may be caused by exceeding the upper limit of recommended therapeutic plasma concentration.…”

InforMatrix®: treatment of rheumatoid arthritis using biologicals

“…When combined with anakinra, an increased incidence of infections was observed. Etanercept did not show interactions with warfarin [87], methotrexate [88] and digoxin [89].…”