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Carvedilol and Digoxin Tablets

Determining the interaction of Carvedilol and Digoxin Tablets and the possibility of their joint administration.

Check result:
Carvedilol <> Digoxin Tablets
Relevance: 19.08.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Using digoxin together with carvedilol may slow your heart rate and lead to increased side effects. Contact your doctor if you experience nausea, vomiting, decreased appetite, diarrhea, confusion, seizures, visual changes, fatigue, irregular heartbeats, and abnormally fast or slow heartbeats. If your doctor does prescribe these medications together, you may need a dose adjustment or special test to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

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.

References
  • Wermeling DP, Field CJ, Smith DA, Chandler MH, Clifton GD, Boyle DA "Effects of long-term oral carvedilol on the steady-state pharmacokinetics of oral digoxin in patients with mild to moderate hypertension." Pharmacotherapy 14 (1994): 600-6
  • "Product Information. Coreg (carvedilol)." SmithKline Beecham, Philadelphia, PA.
  • Eichhorn EJ, Lukas MA, Wu B, Shusterman N "Effect of concomitant digoxin and carvedilol therapy of mortality and morbidity in patients with chronic heart failure." Am J Cardiol 86 (2000): 1032-5
  • Ratnapalan S, Griffiths K, Costei AM, Benson L, Koren G "Digoxin-carvedilol interactions in children." J Pediatr 142 (2003): 572-574
  • Harder S, Brei R, Caspary S, Merz PG "Lack of a pharmacokinetic interaction between carvedilol and digitoxin or phenprocoumon." Eur J Clin Pharmacol 44 (1993): 583-6
  • De Mey C, Brendel E, Enterling D "Carvedilol increases the systemic bioavailability of oral digoxin." Br J Clin Pharmacol 29 (1990): 486-90
  • Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K "Interaction of digoxin with antihypertensive drugs via MDR 1." Life Sci 70 (2002): 1491-1500
Carvedilol

Generic Name: carvedilol

Brand name: Coreg, Coreg CR

Synonyms: n.a.

Digoxin Tablets

Generic Name: digoxin

Brand name: Digitek, Digox, Lanoxin, Lanoxicaps, Cardoxin

Synonyms: Digoxin

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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