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Drug Interactions between Aldactazide and digoxin

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

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Interactions between your drugs

Moderate

digoxin hydroCHLOROthiazide

Applies to: digoxin and Aldactazide (hydrochlorothiazide / spironolactone)

MONITOR: Although diuretics and digitalis glycosides are frequently and appropriately used together, diuretic-induced hypokalemia and hypomagnesemia may predispose patients on digitalis to arrhythmias.

MANAGEMENT: Digoxin, potassium and magnesium levels should be followed closely. Hypokalemia and hypomagnesemia should be treated appropriately. Digitalis dose adjustments may be required. Patients should be advised to notify their physicians if they experience signs of possible digoxin toxicity or electrolyte disturbances, such as weakness, lethargy, muscle pains or cramps, nausea, anorexia, visual disturbances, or irregular heartbeats.

References

  1. Tilstone WJ, Semple PF, Lawson DH, Boyle JA (1977) "Effects of furosemide on glomerular filtration rate and clearance of practolol, digoxin, cephaloridine, and gentamicin." Clin Pharmacol Ther, 22, p. 389-94
  2. Semple P, Tilstone WJ, Lawson DH (1975) "Furosemide and urinary digoxin clearance." N Engl J Med, 293, p. 612-3
  3. Brown DD, Dormois JC, Abraham GN, et al. (1976) "Effect of furosemide on the renal excretion of digoxin." Clin Pharmacol Ther, 20, p. 395-400
  4. McAllister RG, Howell SM, Gomer MS, Selby JB (1976) "Effect of intravenous furosemide on the renal excretion of digoxin." J Clin Pharmacol, 16, p. 110-7
  5. Malcolm AD, Leung FY, Fuchs JC, Duarte JE (1977) "Digoxin kinetics during furosemide administration." Clin Pharmacol Ther, 21, p. 567-74
  6. Waldorff S, Hansen PB, Kjaergard H, Buch J, Egeblad H, Steiness E (1981) "Amiloride-induced changes in digoxin dynamics and kinetics: abolition of digoxin-induced inotropism with amiloride." Clin Pharmacol Ther, 30, p. 172-6
  7. Macolic V, Vrhovac B (1993) "Pharmacokinetics and interactions of digoxin, theophylline and furosemide in diseases with edema." Int J Clin Pharmacol Ther Toxicol, 31, p. 6-11
  8. Whang R, Oei TO, Watanabe A (1985) "Frequency of hypomagnesemia in hospitalized patients receiving digitalis." Arch Intern Med, 145, p. 655-6
  9. Cohen L, Kitzes R (1983) "Magnesium Sulfate and digitalis-toxic arrhythmias." JAMA, 249, p. 2808-10
  10. Leary WP, Reyes AJ (1984) "Drug interactions with diuretics." S Afr Med J, 65, p. 455-61
View all 10 references

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Minor

digoxin spironolactone

Applies to: digoxin and Aldactazide (hydrochlorothiazide / spironolactone)

Spironolactone may reduce the tubular secretion of digoxin. Plasma clearance of digoxin may be decreased, and plasma levels may increase. Also, limited data indicate that spironolactone may have a negative inotropic side effect. Finally, spironolactone may interfere with some digoxin radioimmunoassays, and digoxin concentrations may be overestimated. During coadministration, the patient should be monitored for signs and symptoms of digoxin toxicity, levels should be checked when necessary, and the clinician should keep in mind the possibility that digoxin levels may falsely appear to be elevated. Patients should be advised to notify their physician if they experience nausea, anorexia, visual changes, or irregular heartbeats.

References

  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
View all 19 references

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Drug and food interactions

Moderate

hydroCHLOROthiazide food

Applies to: Aldactazide (hydrochlorothiazide / 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.

References

  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
View all 8 references

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Moderate

spironolactone food

Applies to: Aldactazide (hydrochlorothiazide / 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.

References

  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
View all 8 references

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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

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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.

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