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Drug Interactions between digitoxin and propranolol

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

propranolol digitoxin

Applies to: propranolol and digitoxin

MONITOR: Concomitant use of digitalis glycosides and beta-blockers may increase the risk of bradycardia. These agents slow atrioventricular conduction and decrease heart rate, hence they may have additive cardiac effects during coadministration. Some beta-blockers such as carvedilol, esmolol, and talinolol have also been reported to 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.

MANAGEMENT: Caution is advised during coadministration of digitalis glycosides and beta-blockers. Serum digitalis 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. Beta-blockers should not be used in patients with overt or decompensated congestive heart failure, as sympathetic stimulation may be a vital component in maintaining hemodynamic function in these patients and its inhibition by beta blockade may worsen the heart failure.

References (12)
  1. LeWinter MM, Crawford MH, O'Rourke RA, Karliner JS (1977) "The effects of oral propranolol, digoxin and combination therapy on the resting and exercise electrocardiogram." Am Heart J, 93, p. 202-9
  2. Watt DA (1968) "Sensitivity to propranolol after digoxin intoxication." Br Med J, 2, p. 413-4
  3. De Mey C, Brendel E, Enterling D (1990) "Carvedilol increases the systemic bioavailability of oral digoxin." Br J Clin Pharmacol, 29, p. 486-90
  4. Lowenthal DT, Porter RS, Saris SD, Bies CM, Slegowski MB, Staudacher A (1985) "Clinical pharmacology, pharmacodynamics and interactions with esmolol." Am J Cardiol, 56, f14-8
  5. (2001) "Product Information. Inderal (propranolol)." Wyeth-Ayerst Laboratories
  6. Lowenthal DT, Porter RS, Achari R, Turlapaty P, Laddu AR, Matier WL (1987) "Esmolol-digoxin drug interaction" J Clin Pharmacol, 27, p. 561-6
  7. (2001) "Product Information. Zebeta (bisoprolol)." Lederle Laboratories
  8. Wermeling DP, Field CJ, Smith DA, Chandler MH, Clifton GD, Boyle DA (1994) "Effects of long-term oral carvedilol on the steady-state pharmacokinetics of oral digoxin in patients with mild to moderate hypertension." Pharmacotherapy, 14, p. 600-6
  9. (2001) "Product Information. Coreg (carvedilol)." SmithKline Beecham
  10. Eichhorn EJ, Lukas MA, Wu B, Shusterman N (2000) "Effect of concomitant digoxin and carvedilol therapy of mortality and morbidity in patients with chronic heart failure." Am J Cardiol, 86, p. 1032-5
  11. Ratnapalan S, Griffiths K, Costei AM, Benson L, Koren G (2003) "Digoxin-carvedilol interactions in children." J Pediatr, 142, p. 572-574
  12. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K (2002) "Interaction of digoxin with antihypertensive drugs via MDR 1." Life Sci, 70, p. 1491-1500

Drug and food interactions

Moderate

propranolol food

Applies to: propranolol

ADJUST DOSING INTERVAL: The bioavailability of propranolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take propranolol at the same time each day, preferably with or immediately following meals.

References (2)
  1. Olanoff LS, Walle T, Cowart TD, et al. (1986) "Food effects on propranolol systemic and oral clearance: support for a blood flow hypothesis." Clin Pharmacol Ther, 40, p. 408-14
  2. Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ (1984) "Stable oral availability of sustained release propranolol when co-administered with hydralazine or food: evidence implicating substrate delivery rate as a determinant of presystemic drug interactions." Br J Clin Pharmacol, 17, s45-50
Moderate

propranolol food

Applies to: propranolol

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References (1)
  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E (1981) "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther, 30, p. 429-35
Moderate

propranolol food

Applies to: propranolol

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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