No interaction between nebivolol and digoxin in healthy volunteers

Abstract

Background Nebivolol is a new generation cardiovascular agent reported to have vasodilating actions owing to its ability to potentiate nitric oxide release from the endothelium coupled with highly cardioselective β1‐adrenergic antagonism. It has been studied worldwide in a variety of disorders such as hypertension, CHF and angina. As concomitant administration of nebivolol with digoxin is likely to occur when nebivolol becomes commercially available, the effect of nebivolol on the pharmacokinetics (PK) of digoxin was assessed in 13 healthy volunteers. Methods Subjects received a 0.25 mg oral loading dose of digoxin BID on Day 1 followed by QD on Days 2–17. On Days 8–17, subjects also received a QD dose of 10 mg nebivolol. Blood samples for PK assessment of digoxin were taken at frequent intervals on Days 7 and 17. Results Administration of nebivolol resulted in no clinically significant changes in the PK of digoxin (Cmax: Ratio 1.07, 90% CI 0.94–1.21; AUC0–24hr: Ratio 1.08, 90% CI 1.03–1.14). Moreover, there was no evidence of any cardiovascular or laboratory test result abnormalities. Conclusions No clinically significant changes in the PK of digoxin were observed with the co‐administration of nebivolol. Therefore, no dose adjustments are considered necessary for digoxin when given concomitantly with nebivolol. Clinical Pharmacology & Therapeutics (2005) 77, P76–P76; doi:

Nebivolol: Pharmacologic Profile of an Ultraselective, Vasodilatory β1‐Blocker

“…These results are particularly important because β‐blockers are often used with diuretics and ACE inhibitors for the treatment of CHD and HF. In addition, coadministration of nebivolol with spironolactone and digoxin, which are also commonly used with β‐blockers to treat severe HF, caused no clinically significant pharmacokinetic interactions 61 , 62 . Because warfarin is known to have numerous drug‐drug interactions of clinical significance, the effect of the coadministration of nebivolol on the pharmacokinetic and anticoagulant actions of warfarin was studied in 12 healthy volunteers 63 .…”

Nebivolol

“…[63][64][65][66][67][68][69][70] However, 3-fold increases in nebivolol peak plasma concentrations and 8-fold increases in area under the curve occur during concomitant administration with fluoxetine, a known CYP2D6 inhibitor, and therefore caution should be exercised when administering nebivolol and any CYP2D6 inhibitor in hypertensive patients. 71 Given the negative chronotropic and inotropic properties and the antihypertensive effects of nebivolol, it is likely that a pharmacodynamic interaction may exist between nebivolol and other agents with similar properties.…”