Drug Interactions between Coreg and digitoxin

Consumer information for this interaction is not currently available.

MONITOR: Concomitant use of digitalis glycosides and carvedilol may increase the risk of bradycardia as well as the concentration and possible toxicity of digoxin. These agents slow atrioventricular conduction and decrease heart rate; hence, they may have additive cardiac effects when coadministered. Pharmacokinetically, carvedilol has been shown to modestly increase the systemic bioavailability of oral digoxin, but no pharmacokinetic interaction has been reported between carvedilol and digitoxin or intravenous forms of digoxin in single dose studies. The mechanism may involve enhanced absorption as well as reduced renal excretion of digoxin due to inhibition of intestinal and renal P-glycoprotein efflux transporters by carvedilol. In a study of 12 patients with mild to moderate hypertension, coadministration of digoxin (0.25 mg once daily) and carvedilol (25 mg daily) for two weeks increased steady state mean digoxin peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 32%, 14% and 16%, respectively, compared to administration of digoxin alone. In another study, administration of a single oral dose of digoxin (0.5 mg) with carvedilol (25 mg) in 8 healthy male volunteers resulted in a 60% increase in digoxin Cmax and a 20% increase in digoxin AUC compared to administration with placebo. Another study also demonstrated possible gender differences. In 24 patients receiving digoxin (0.0625 mg to 0.25 mg/day) for heart failure, administration of carvedilol (6.25 mg twice a day) led to a 37% increase in digoxin Cmax and a 56% increase in digoxin AUC in male patients, while no significant changes were observed in female patients. The interaction may be more pronounced in pediatric patients. Oral digoxin clearance decreased by 50% in eight children ages 2 weeks to 8 years old following the addition of carvedilol, and digoxin toxicity occurred in two of those patients.

MANAGEMENT: Caution is advised when initiating, adjusting, or discontinuing carvedilol in patients on digitalis glycosides, though they are frequently used together in clinical practice. Serum digoxin levels, heart rate, and blood pressure should be monitored closely, particularly during the first few weeks of concomitant therapy and following changes in the dosing regimen. The labeling of some oral dosage forms of digoxin recommends a reduction in digoxin's dose of 15% to 30% or a modification in the dosing frequency of digoxin when carvedilol is initiated. Patients should be closely monitored for and advised on the signs and symptoms of digoxin toxicity such as anorexia, nausea, visual changes, irregular heartbeat, slow pulse, dizziness, or syncope. This may be especially important in children and patients with renal impairment and/or electrolyte disturbances, who may be more susceptible to digoxin toxicity. Consultation with digoxin product labeling for more specific guidance may be advisable.