Drug Interactions between Cardoxin and Coreg

MONITOR: Concomitant use of digitalis glycosides and beta-blockers including carvedilol may increase the risk of bradycardia. These agents slow atrioventricular conduction and decrease heart rate, hence they may have additive cardiac effects during coadministration. Pharmacokinetically, carvedilol has been shown to modestly increase the systemic bioavailability of digoxin. The mechanism may involve enhanced absorption as well as reduced renal excretion of digoxin due to inhibition of intestinal and renal P-glycoprotein efflux transporter 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 once 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. The 24-hour urinary excretion and 24-hour renal clearance of digoxin also increased by 45% and 26%, respectively. 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. These changes are not considered clinically significant. However, the interaction may be more pronounced in pediatric patients. Oral digoxin clearance decreased by 50% in eight children ages 2 weeks to 8 years following the addition of carvedilol, and digoxin toxicity occurred in two. Another study also demonstrated possible gender differences. In 24 patients receiving digoxin (0.0625 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. No pharmacokinetic interaction has been reported for digitoxin or intravenous digoxin when administered with carvedilol in single-dose studies.

MANAGEMENT: Caution is advised during coadministration of digitalis glycosides and beta-blockers. Serum digoxin levels, heart rate, and blood pressure should be monitored closely, particularly during the first few weeks of concomitant therapy. Patients should be advised to notify their physician if they experience anorexia, nausea, visual changes, irregular heartbeat, slow pulse, dizziness, or syncope. Although they are often used together in clinical practice, the addition of carvedilol to a stabilized digoxin regimen should prompt a closer monitoring of serum digoxin levels. This may be especially important in children and patients with renal impairment and/or electrolyte disturbances, who may be more susceptible to digoxin toxicity. Some investigators have recommended an initial reduction in digoxin dosage of at least 25% if carvedilol is coadministered in pediatric patients.

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