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Drug Interactions between Lanoxicaps and spironolactone

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

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Interactions between your drugs

Major

digoxin spironolactone

Applies to: Lanoxicaps (digoxin) and spironolactone

ADJUST DOSE: Coadministration with spironolactone may increase the exposure and toxicity of digoxin, as well as interfere with some digoxin radioimmunoassays. The exact mechanism by which digoxin exposure is increased is unknown, but may involve reduced tubular secretion of digoxin due to inhibition of the P-glycoprotein (P-gp) efflux transporter by spironolactone. It has also been reported that some laboratory tests may falsely detect spironolactone as digoxin at levels up to 0.5 ng/mL, resulting in falsely elevated digoxin levels. In 6 healthy subjects, administration of digoxin (0.5 mg to 1 mg orally for 6 days followed by an intravenous dose 0.7 times the oral dose on day 7) in combination with spironolactone (200 mg daily) resulted in decreased renal and plasma clearance of digoxin by an average of 13% when compared to administration of digoxin alone. Another study reported that spironolactone increased the maximum plasma concentration (Cmax) and systemic exposure (AUC) of a single dose of digoxin by 55% and 18%, respectively, when compared to digoxin administered alone. This study reported that digoxin's renal clearance decreased by approximately 11%. Some studies have reported an increase in digoxin's AUC of up to 44% when used in combination with spironolactone. However, despite this interaction, the safe use of digoxin in combination with spironolactone in patients with heart failure has been described in the clinical trial setting.

MANAGEMENT: Serum digoxin concentrations should be measured prior to initiating spironolactone and digoxin's dose may need to be decreased by approximately 15% to 30% or the dosing frequency may need to be modified in order to maintain digoxin's concentration within the goal range. Caution and closer monitoring of digoxin levels, and signs and symptoms of digoxin toxicity are advised when this combination is used. As certain digoxin radioimmunoassays may be falsely elevated in the presence of spironolactone, it may be advisable to discuss which assay is being used to monitor digoxin and consider an alternative test if the patient's laboratory values do not seem to match the clinical state of the patient.

References (26)
  1. Wirth KE, Frolich JC, Hollifield JW, et al. (1976) "Metabolism of digitoxin in man and its modification by spironolactone." Eur J Clin Pharmacol, 9, p. 345-54
  2. Rodin SM, Johnson BF (1988) "Pharmacokinetic interactions with digoxin." Clin Pharmacokinet, 15, p. 227-44
  3. Hedman A, Angelin B, Arvidsson A, Dahlqvist R (1992) "Digoxin-interactions in man: spironolactone reduces renal but not biliary digoxin clearance." Eur J Clin Pharmacol, 42, p. 481-5
  4. Morris RG, Lagnado PY, Lehmann DR, et al. (1987) "Spironolactone as a source of interference in commercial digoxin immunoassays." Ther Drug Monit, 9, p. 208-11
  5. Fenster PE, Hager WD, Goodman MM (1984) "Digoxin-quinidine-spironolactone interaction." Clin Pharmacol Ther, 36, p. 70-3
  6. Waldorff S, Hansen PB, Egeblad H, et al. (1983) "Interactions between digoxin and potassium-sparing diuretics." Clin Pharmacol Ther, 33, p. 418-23
  7. de Cos MA, Gomez-Ullate J, Gomez F, Armijo JA (1992) "Time course of trough serum gentamicin concentrations in preterm and term neonates." Clin Pharmacokinet, 23, p. 391-401
  8. Finnegan TP, Spence JD, Cape RD (1984) "Potassium-sparing diuretics: interaction with digoxin in elderly men." J Am Geriatr Soc, 32, p. 129-31
  9. Paladino JA, Davidson KH, McCall BB (1984) "Influence of spironolactone on serum digoxin concentration ." JAMA, 251, p. 470-1
  10. Hsieh YY, Lin MS, Chen JH, et al. (1983) "Spironolactone-digoxin interaction." Taiwan I Hsueh Hui Tsa Chih, 82, p. 47-60
  11. Marcus FI (1985) "Pharmacokinetic interactions between digoxin and other drugs." J Am Coll Cardiol, 5, a82-90
  12. DiPiro JT, Cote JR, DiPiro CR, Bustrack JA (1980) "Spironolactone interference with digoxin radioimmunoassay in cirrhotic patients." Am J Hosp Pharm, 37, p. 1518-21
  13. Thomas RW, Maddox RR (1981) "The interaction of spironolactone and digoxin: a review and evaluation." Ther Drug Monit, 3, p. 117-20
  14. Carruthers SG, Dujovne CA (1980) "Cholestyramine and spironolactone and their combination in digitoxin elimination." Clin Pharmacol Ther, 27, p. 184-7
  15. Whang R, Oei TO, Watanabe A (1985) "Frequency of hypomagnesemia in hospitalized patients receiving digitalis." Arch Intern Med, 145, p. 655-6
  16. Cohen L, Kitzes R (1983) "Magnesium Sulfate and digitalis-toxic arrhythmias." JAMA, 249, p. 2808-10
  17. Waldorff S, Andersen JD, Heeboll-Nielsen N, et al. (1978) "Spironolactone-induced changes in digoxin kinetics." Clin Pharmacol Ther, 24, p. 162-7
  18. 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
  19. 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
  20. (2022) "Product Information. PMS-Digoxin (digoxin)." Pharmascience Inc
  21. (2024) "Product Information. Teva-Spironolactone (spironolactone)." Teva Canada Limited
  22. (2023) "Product Information. CaroSpir (spironolactone)." Carolina Medical Products Company, SUPPL-6
  23. (2025) "Product Information. Digoxin (digoxin)." Hikma Pharmaceuticals USA Inc.
  24. (2025) "Product Information. Lanoxin (digoxin)." Covis Pharmaceuticals
  25. (2024) "Product Information. Digoxin (digoxin)." Amneal Pharmaceuticals LLC
  26. (2025) "Product Information. Digoxin (digoxin)." Aurobindo Pharma USA Inc

Drug and food/lifestyle interactions

Moderate

spironolactone food/lifestyle

Applies to: spironolactone

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References (10)
  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
  9. (2023) "Product Information. Buprenorphine (buprenorphine)." G.L. Pharma UK Ltd
  10. (2023) "Product Information. Temgesic (buprenorphine)." Reckitt Benckiser Pty Ltd
Minor

digoxin food/lifestyle

Applies to: Lanoxicaps (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

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

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