Skip to main content

Drug Interactions between dextromethorphan / quinidine and digoxin

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

quiNIDine dextromethorphan

Applies to: dextromethorphan / quinidine and dextromethorphan / quinidine

GENERALLY AVOID: Coadministration with potent CYP450 2D6 inhibitors (e.g., quinidine, terbinafine) may significantly increase the plasma concentrations of dextromethorphan in patients who are extensive metabolizers of this isoenzyme (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). The proposed mechanism is inhibition of the CYP450 2D6-mediated O-demethylation of dextromethorphan. Studies in humans have shown an increase in systemic exposure of dextromethorphan of up to 43-fold when given concurrently with quinidine. Increased plasma concentrations increase the risk of dextromethorphan-related adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome. However, this interaction has also been used clinically, with dextromethorphan in combination with quinidine indicated by some authorities for the treatment of pseudobulbar affect. Data evaluating the impact of this interaction in patients who are poor metabolizers of CYP450 2D6 are limited; most studies include extensive metabolizers of this isoenzyme. It is expected that poor metabolizers would have elevated dextromethorphan levels without concurrent quinidine

MANAGEMENT: The combination of dextromethorphan with potent CYP450 2D6 inhibitors should be generally avoided. Some manufacturers consider the concomitant use of dextromethorphan and selective serotonin reuptake inhibitors contraindicated. If use is considered necessary, the patient should be monitored for signs of dextromethorphan adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome, and advised to notify their health care professional if these adverse effects develop or worsen. Dose reduction of dextromethorphan may also be required.

References (6)
  1. Zhang Y, Britto MR, Valderhaug KL, Wedlund PJ, Smith RA (1992) "Dextromethorphan: enhancing its systemic availability by way of low-dose quinidine-mediated inhibition of cytochrome P4502D6." Clin Pharmacol Ther, 51, p. 647-55
  2. Schadel M, Wu DA, Otton SV, Kalow W, Sellers EM (1995) "Pharmacokinetics of dextromethorphan and metabolites in humans: influence of the CYP2d6 phenotype and quinidine inhibition." J Clin Psychopharmacol, 15, p. 263-9
  3. Capon DA, Bochner F, Kerry N, Mikus G, Danz C, Somogyi AA (1996) "The influence of CYP2d6 polymorphism and quinidine on the disposition and antitussive effect of dextromethorphan in humans." Clin Pharmacol Ther, 60, p. 295-307
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Cerner Multum, Inc. "Australian Product Information."
  6. (2010) "Product Information. Nuedexta (dextromethorphan-quinidine)." Avanir Pharmaceuticals, Inc
Major

quiNIDine digoxin

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

Drug and food interactions

Moderate

quiNIDine food

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

dextromethorphan food

Applies to: dextromethorphan / quinidine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
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 (2)
  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

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:

  • dextromethorphan/quinidine
  • digoxin

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