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Drug Interactions between Digox and Quinaglute Dura-Tabs

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

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Interactions between your drugs

Major

quiNIDine digoxin

Applies to: Quinaglute Dura-Tabs (quinidine) and Digox (digoxin)

ADJUST DOSE: Quinidine significantly increases serum digoxin levels in more than 90% of patients. The proposed mechanism is quinidine inhibition of the P-glycoprotein-mediated intestinal efflux and/or renal tubular secretion of digoxin. Serum digoxin levels may increase 2-fold on average, although the interaction is subject to a high degree of interpatient variability.

MANAGEMENT: Caution is advised if digoxin must be used in combination with quinidine. Empiric reduction in digoxin dosing may be appropriate at the initiation of quinidine therapy. Serum digoxin levels and pharmacologic effects should be closely monitored, and the dosage adjusted accordingly. Patients should be advised to notify their physician if they experience signs of digitalis toxicity such as nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeats.

References

  1. Pedersen KE, Christiansen BD, Klitgaard NA, Nielsen-Kudsk F "Effect of quinidine on digoxin bioavailability." Eur J Clin Pharmacol 24 (1983): 41-7
  2. Williams PJ, Lane J, Murray W, et al. "Pharmacokinetics of digoxin-quinidine interaction via mixed-effect modelling." Clin Pharmacokinet 22 (1992): 66-74
  3. Hager WD, Fenster P, Mayersohn M, et al. "Digoxin-quinidine interaction: pharmacokinetic evaluation." N Engl J Med 300 (1979): 1238-41
  4. Schenck-Gustafsson K, Jogestrand T, Nordlander R, Dahlqvist R "Effect of quinidine on digoxin concentration in skeletal muscle and serum in patients with atrial fibrillation." N Engl J Med 305 (1981): 209-11
  5. Hager WD, Mayersohn M, Graves PE "Digoxin bioavailability during quinidine administration." Clin Pharmacol Ther 30 (1981): 594-9
  6. Schenck-Gustafsson K, Dahlqvist R "Pharmacokinetics of digoxin in patients subjected to the quinidine-digoxin interaction." Br J Clin Pharmacol 11 (1981): 181-6
  7. Belz GG, Doering W, Munkes R, Matthews J "Interaction between digoxin and calcium antagonists and antiarrhythmic drugs." Clin Pharmacol Ther 33 (1983): 410-7
  8. Rodin SM, Johnson BF "Pharmacokinetic interactions with digoxin." Clin Pharmacokinet 15 (1988): 227-44
  9. Pedersen KE, Hastrup J, Hvidt S "The effect of quinidine on digoxin kinetics in cardiac patients." Acta Med Scand 207 (1980): 291-5
  10. Walker AM, Cody RJ Jr, Greenblatt DJ, Jick H "Drug toxicity in patients receiving digoxin and quinidine." Am Heart J 105 (1983): 1025-8
  11. Leahey EB Jr, Bigger JT Jr, Butler VP Jr, et al. "Quinidine-digoxin interaction: time course and pharmacokinetics." Am J Cardiol 48 (1981): 1141-6
  12. Hirsh PD, Weiner HJ, North RL "Further insights into digoxin-quinidine interaction: lack of correlation between serum digoxin concentration and inotropic state of the heart." Am J Cardiol 46 (1980): 863-8
  13. Fenster PE, Hager WD, Perrier D, et al. "Digoxin-quinidine interaction in patients with chronic renal failure." Circulation 66 (1982): 1277-80
  14. Fenster PE, Hager WD, Goodman MM "Digoxin-quinidine-spironolactone interaction." Clin Pharmacol Ther 36 (1984): 70-3
  15. Das G, Barr CE, Carlson J "Reduction of digoxin effect during the digoxin-quinidine interaction." Clin Pharmacol Ther 35 (1984): 317-21
  16. Angelin B, Arvidsson A, Dahlqvist R, et al. "Quinidine reduces biliary clearance of digoxin in man." Eur J Clin Invest 17 (1987): 262-5
  17. Pieroni RE, Marshall J "Fatal digoxin-quinidine interaction in an elderly woman." J Am Geriatr Soc 29 (1981): 422-5
  18. Hirschberg R, Schaefer K, von Herrath D, et al. "Digoxin-quinidine interaction in patients with renal failure." Klin Wochenschr 59 (1981): 521-2
  19. Nigam SK, Burton ME, Vasko MR "Quinidine-induced digoxin toxicity after discontinuing digoxin in a patient with renal failure." Clin Pharm 3 (1984): 662-4
  20. Doering W "Effect of coadministration of verapamil and quinidine on serum digoxin concentration." Eur J Clin Pharmacol 25 (1983): 517-21
  21. Rameis H "Quinidine-digoxin interaction: are the pharmacokinetics of both drugs altered?" Int J Clin Pharmacol Ther Toxicol 23 (1985): 145-53
  22. Holt DW, Hayler AM, Edmonds ME, Ashford RF "Clinically significant interaction between digoxin and quinidine." Br Med J 2 (1979): 1401
  23. Doering W "Quinidine-digoxin interaction: Pharmacokinetics, underlying mechanism and clinical implications." N Engl J Med 301 (1979): 400-4
  24. De Lannoy IA, Koren G, Klein J, et al. "Cyclosporin and quinidine inhibition of renal digoxin excretion: evidence for luminal secretion of digoxin." Am J Physiol 263 (1992): f613-22
  25. Dahlqvist R, Ejvinsson G, Schenck-Gustafsson K "Effect of quinidine on plasma concentration and renal clearance of digoxin: a clinically important drug interaction." Br J Clin Pharmacol 9 (1980): 413-8
  26. Bigger JT Jr, Leahey EB Jr "Quinidine and digoxin: an important interaction." Drugs 24 (1982): 229-39
  27. Fichtl B, Doering W, Seidel H "The quinidine-digoxin interaction in patients with impaired renal function." Int J Clin Pharmacol Ther Toxicol 21 (1983): 229-33
  28. Marcus FI "Pharmacokinetic interactions between digoxin and other drugs." J Am Coll Cardiol 5 (1985): a82-90
  29. Mungall DR, Robichaux RP, Perry W, et al. "Effects of quinidine on serum digoxin concentration: a prospective study." Ann Intern Med 93 (1980): 689-93
  30. Mordel A, Halkin H, Zulty L, Almog S, Ezra D "Quinidine enhances digitalis toxicity at therapeutic serum digoxin levels." Clin Pharmacol Ther 53 (1993): 457-62
  31. Freitag D, Bebee R, Sunderland B "Digoxin-quinidine and digoxin-amiodarone interactions: frequency of occurrence and monitoring in australian repatriation hospitals." J Clin Pharm Ther 20 (1995): 179-83
  32. Bauer LA, Horn JR, Pettit H "Mixed-effect modeling for detection and evaluation of drug interactions: digoxin-quinidine and digoxin-verapamil combinations." Ther Drug Monit 18 (1996): 46-52
  33. Drescher S, Glaeser H, Murdter T, Hitzl M, Eichelbaum M, Fromm MF "P-glycoprotein-mediated intestinal and biliary digoxin transport in humans." Clin Pharmacol Ther 73 (2003): 223-31
  34. Balayssac D, Authier N, Cayre A, Coudore F "Does inhibition of P-glycoprotein lead to drug-drug interactions?" Toxicol Lett 156 (2005): 319-29
View all 34 references

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Drug and food interactions

Moderate

quiNIDine food

Applies to: Quinaglute Dura-Tabs (quinidine)

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References

  1. Ace LN, Jaffe JM, Kunka RL "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos 4 (1983): 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol 36 (1996): 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol 48 (1995): 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
View all 4 references

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Minor

digoxin food

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

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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:

  • Digox (digoxin)
  • Quinaglute Dura-Tabs (quinidine)

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

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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

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

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