Skip to main content

Drug Interactions between digoxin and Pacerone

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

amiodarone digoxin

Applies to: Pacerone (amiodarone) and digoxin

ADJUST DOSE: Coadministration with amiodarone may increase serum digoxin concentrations by up to 100%, frequently resulting in clinical toxicity. In children, this percentage may be even higher. Amiodarone has been suggested to increase intestinal transit time, reduce renal clearance and volume of distribution, displace digoxin from protein binding sites, as well as induce hypothyroidism, all of which may contribute to increased serum digoxin levels. In addition, both drugs may have additive bradycardic effects. Torsade de pointes cardiac arrhythmia has been reported. The interaction also has occurred with digitoxin.

MANAGEMENT: The need for continued digitalis therapy should be evaluated if amiodarone is prescribed to patients treated with digitalis. Empirical reduction of digitalis dosage by one-third to one-half should be considered in patients who require concomitant treatment with these drugs. Serum digitalis levels should be closely monitored and patients observed for clinical evidence of toxicity. Patients should be advised to seek medical attention if they experience signs of digitalis toxicity such as nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeats.

References

  1. Kerin NZ, Aragon E, Faitel K, Frumin H, Rubenfire M (1989) "Long-term efficacy and toxicity of high- and low-dose amiodarone regimens." J Clin Pharmacol, 29, p. 418-23
  2. Wilson JS, Podrid PJ (1991) "Side effects from amiodarone." Am Heart J, 121, p. 158-71
  3. Gill J, Heel RC, Fitton A (1992) "Amiodarone: an overview of its pharmacological properties, and review of its therapeutic use in cardiac arrhythmias." Drugs, 43, p. 69-110
  4. Oetgen WJ, Sobol SM, Tri TB, Heydorn WH, Rakita L (1984) "Amiodarone-digoxin interaction: clinical and experimental observations." Chest, 86, p. 75-9
  5. Nademanee K, Kannan R, Hendrickson J, Ookhtens M, Kay I, Singh BN (1984) "Amiodarone-digoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms and therapeutic implications." J Am Coll Cardiol, 4, p. 111-6
  6. Rodin SM, Johnson BF (1988) "Pharmacokinetic interactions with digoxin." Clin Pharmacokinet, 15, p. 227-44
  7. Klein HO, Beker B, DiSegni E, Kaplinsky E (1987) "Asystole produced by the combination of amiodarone and digoxin." Am Heart J, 113, p. 399-400
  8. Ben-Chetrit E, Ackerman Z, Eliakim M (1985) "Amiodarone-associated hypothyroidism--a possible cause of digoxin intoxication." Am J Med Sci, 289, p. 114-6
  9. McGovern B, Garan H, Kelly E, Ruskin JN (1983) "Adverse reactions during treatment with amiodarone hydrochloride." Br Med J (Clin Res Ed), 287, p. 175-80
  10. Fenster PE, White NW, Jr Hanson CD (1985) "Pharmacokinetic evaluation of the digoxin-amiodarone interaction." J Am Coll Cardiol, 5, p. 108-12
  11. Bajaj BP, Baig MW, Perrins EJ (1991) "Amiodarone-induced torsades de pointes: the possible facilitatory role of digoxin." Int J Cardiol, 33, p. 335-7
  12. Marcus FI (1985) "Pharmacokinetic interactions between digoxin and other drugs." J Am Coll Cardiol, 5, a82-90
  13. Moysey JO, Jaggarao NS, Grundy EN, Chamberlain DA (1981) "Amiodarone increases plasma digoxin concentrations." Br Med J (Clin Res Ed), 282, p. 272
  14. Koren G, Hesslein PS, MacLeod SM (1984) "Digoxin toxicity associated with amiodarone therapy in children." J Pediatr, 104, p. 467-70
  15. (2002) "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories
  16. Mingardi G (1984) "Amiodarone and plasma digoxin levels." Lancet, 1, p. 1238
  17. Freitag D, Bebee R, Sunderland B (1995) "Digoxin-quinidine and digoxin-amiodarone interactions: frequency of occurrence and monitoring in australian repatriation hospitals." J Clin Pharm Ther, 20, p. 179-83
  18. Laer S, Scholz H, Buschmann I, Thoenes M, Meinertz T (1998) "Digitoxin intoxication during concomitant use of amiodarone." Eur J Clin Pharmacol, 54, p. 95-6
  19. Drescher S, Glaeser H, Murdter T, Hitzl M, Eichelbaum M, Fromm MF (2003) "P-glycoprotein-mediated intestinal and biliary digoxin transport in humans." Clin Pharmacol Ther, 73, p. 223-31
View all 19 references

Switch to consumer interaction data

Drug and food interactions

Major

amiodarone food

Applies to: Pacerone (amiodarone)

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered amiodarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 11 nonsmoking, healthy volunteers, grapefruit juice (300 mL with drug administration, then 3 hours and 9 hours later) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amiodarone (17 mg/kg single dose) by 84% and 50%, respectively, compared to water. Formation of the pharmacologically active metabolite, N-desethylamiodarone (N-DEA), was completely inhibited. Clinically, this interaction can lead to altered efficacy of amiodarone, since antiarrhythmic properties of amiodarone and N-DEA appear to differ. In the study, mean increases in PR and QTc intervals of 17.9% and 11.3%, respectively, were observed 6 hours postdose with water, while increases of 10.2% and 3.3%, respectively, were observed after administration with grapefruit juice.

ADJUST DOSING INTERVAL: Food increases the rate and extent of absorption of amiodarone. The mechanism appears to involve the effect of food-induced physiologic changes on drug release from its formulation. In 30 healthy volunteers, administration of a single 600 mg dose of amiodarone following a high-fat meal resulted in a Cmax and AUC that were 3.8 and 2.4 times the respective values under fasting conditions. The time to reach peak plasma concentration (Tmax) was decreased by 37%, indicating an increased rate of absorption. Mean Cmax and AUC for the active metabolite, N-DEA, also increased by 32% and 55%, respectively, but there was no change in the Tmax.

MANAGEMENT: Patients treated with oral amiodarone should avoid consumption of grapefruits and grapefruit juice. In addition, oral amiodarone should be administered consistently with regard to meals.

References

  1. (2002) "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories
  2. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  3. Meng X, Mojaverian P, Doedee M, Lin E, Weinryb I, Chiang ST, Kowey PR (2001) "Bioavailability of Amiodarone tablets administered with and without food in healthy subjects." Am J Cardiol, 87, p. 432-5

Switch to consumer interaction data

Minor

digoxin food

Applies to: digoxin

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.

References

  1. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
  2. Becquemont L, Verstuyft C, Kerb R, et al. (2001) "Effect of grapefruit juice on digoxin pharmacokinetics in humans." Clin Pharmacol Ther, 70, p. 311-6

Switch to consumer interaction data

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antiarrhythmics

Therapeutic duplication

The recommended maximum number of medicines in the 'antiarrhythmics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antiarrhythmics' category:

  • digoxin
  • Pacerone (amiodarone)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

Report options

Loading...
QR code containing a link to this page

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer