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Drug Interactions between digoxin and enalapril / hydrochlorothiazide

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

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Interactions between your drugs

Moderate

enalapril digoxin

Applies to: enalapril / hydrochlorothiazide and digoxin

MONITOR: Some ACE inhibitors may decrease the renal clearance of digoxin. Increased plasma digoxin levels may result. The proposed mechanism is reduced tubular secretion of digoxin. Some occurrences of decreased digoxin levels also have been reported. Patients with congestive heart failure (CHF) or renal impairment may have a greater risk of developing digoxin toxicity.

MANAGEMENT: While this combination has demonstrated benefits in some CHF patients, their clinical response and digoxin levels should be monitored. Patients should be advised to notify their physician if they experience nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeats.

References

  1. Miyakawa T, Shionoiri H, Takasaki I, et al. (1991) "The effect of captopril on pharmacokinetics of digoxin in patients with mild congestive heart failure." J Cardiovasc Pharmacol, 17, p. 576-80
  2. Rodin SM, Johnson BF (1988) "Pharmacokinetic interactions with digoxin." Clin Pharmacokinet, 15, p. 227-44
  3. Douste-Blazy P, Blanc M, Montastruc JL, et al. (1986) "Is there any interaction between digoxin and enalapril?" Br J Clin Pharmacol, 22, p. 752-3
  4. Doering W, Maass L, Irmisch R, Konig E (1987) "Pharmacokinetic interaction study with ramipril and digoxin in healthy volunteers." Am J Cardiol, 59, d60-4
  5. Kromer EP, Elsner D, Riegger GA (1990) "Digoxin, converting-enzyme inhibition (quinapril), and the combination in patients with congestive heart failure functional class II and sinus rhythm." J Cardiovasc Pharmacol, 16, p. 9-14
  6. Cleland JG, Dargie HJ, Pettigrew A, Gillen G, Robertson JI (1986) "The effects of captopril on serum digoxin and urinary urea and digoxin clearances in patients with congestive heart failure." Am Heart J, 112, p. 130-5
  7. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
View all 7 references

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Moderate

enalapril hydroCHLOROthiazide

Applies to: enalapril / hydrochlorothiazide and enalapril / hydrochlorothiazide

MONITOR: Although they are frequently combined in clinical practice, diuretics and angiotensin converting enzyme (ACE) inhibitors may have additive effects. Coadministration makes hypotension and hypovolemia more likely than does either drug alone. Some ACE inhibitors may attenuate the increase in the urinary excretion of sodium caused by some loop diuretics. Some patients on diuretics, especially those on dialysis or a dietary salt restriction, may experience acute hypotension with lightheadedness and dizziness after receiving the first dose of the ACE inhibitor. In addition, ACE inhibitors may cause renal insufficiency or acute renal failure in patients with sodium depletion or renal artery stenosis.

MANAGEMENT: Monitoring of blood pressure, diuresis, electrolytes, and renal function is recommended during coadministration. The possibility of first-dose hypotensive effects may be minimized by initiating therapy with small doses of the ACE inhibitor, or either discontinuing the diuretic temporarily or increasing the salt intake approximately one week prior to initiating an ACE inhibitor. Alternatively, the patient may remain under medical supervision for at least two hours after the first dose of the ACE inhibitor, or until blood pressure has stabilized.

References

  1. Reader C, Peyregne EA, Suarez LD (1983) "Amrinone therapy in congestive cardiomyopathy." Am Heart J, 105, p. 1045
  2. Fujimura A, Shimokawa Y, Ebihara A (1990) "Influence of captopril on urinary excretion of furosemide in hypertensive subjects." J Clin Pharmacol, 30, p. 538-42
  3. Funck-Brentano C, Chatellier G, Alexandre JM (1986) "Reversible renal failure after combined treatment with enalapril and furosemide in a patient with congestive heart failure." Br Heart J, 55, p. 596-8
  4. Weisser K, Schloos J, Jakob S, et al. (1992) "The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients." Eur J Clin Pharmacol, 43, p. 173-7
  5. Motwani JG, Fenwick MK, Morton JJ, Struthers AD (1992) "Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure." Circulation, 86, p. 439-45
  6. Burnakis TG, Mioduch HJ (1984) "Combined therapy with captopril and potassium supplementation: a potential for hyperkalemia." Arch Intern Med, 144, p. 2371-2
  7. Murphy BF, Whitworth JA, Kincaid-Smith P (1984) "Renal insufficiency with combinations of angiotensin converting enzyme inhibitors and diuretics." Br Med J, 288, p. 844-5
  8. Thind GS (1985) "Renal insufficiency during angiotensin-converting enzyme inhibitor therapy in hypertensive patients with no renal artery stenosis." J Clin Hypertens, 1, p. 337-43
  9. Radley AS, Fitzpatrick RW (1987) "An evaluation of the potential interaction between enalapril and amiloride." J Clin Pharm Ther, 12, p. 319-23
  10. Champ JD (1993) "Case report: azotemia secondary to enalapril and diuretic use and the diagnosis of renovascular hypertension." Am J Med Sci, 305, p. 25-7
  11. Hume AL, Murphy JL, Lauerman SE (1989) "Angiotensin-converting enzyme inhibitor-induced cough." Pharmacotherapy, 9, p. 88-90
  12. Lee HB, Blaufox MD (1992) "Renal functional response to captopril during diuretic therapy." J Nucl Med, 33, p. 739-43
  13. DeQuattro V (1991) "Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide." Clin Cardiol, 14, iv28-32;
  14. (2002) "Product Information. Vasotec (enalapril)." Merck & Co., Inc
  15. McLay JS, McMurray JJ, Bridges AB, Fraser CG, Struthers AD (1993) "Acute effects of captopril on the renal actions of furosemide in patients with chronic heart failure." Am Heart J, 126, p. 879-86
  16. Sudoh T, Fujimura A, Shiga T, et al. (1993) "Influence of lisinopril on urinary electrolytes excretion after furosemide in healthy subjects." J Clin Pharmacol, 33, p. 640-3
  17. Lederle RM (1985) "Captopril and hydrochlorothiazide in the fixed combination multicenter trial." J Cardiovasc Pharmacol, 7, S63-9
  18. (2001) "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc
  19. Good JM, Brady AJ, Noormohamed FH, Oakley CM, Cleland JG (1994) "Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition." Circulation, 90, p. 220-4
  20. (2001) "Product Information. Capoten (captopril)." Bristol-Myers Squibb
  21. (2001) "Product Information. Lexxel (enalapril-felodipine)." Astra-Zeneca Pharmaceuticals
  22. "Product Information. Zestril (lisinopril)." Astra-Zeneca Pharmaceuticals
  23. Cerner Multum, Inc. "Australian Product Information."
View all 23 references

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Moderate

digoxin hydroCHLOROthiazide

Applies to: digoxin and enalapril / hydrochlorothiazide

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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Drug and food interactions

Moderate

enalapril food

Applies to: enalapril / hydrochlorothiazide

GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes.

References

  1. (2002) "Product Information. Vasotec (enalapril)." Merck & Co., Inc
  2. Good CB, McDermott L (1995) "Diet and serum potassium in patients on ACE inhibitors." JAMA, 274, p. 538
  3. Ray K, Dorman S, Watson R (1999) "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens, 13, p. 717-20

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Moderate

enalapril food

Applies to: enalapril / hydrochlorothiazide

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

hydroCHLOROthiazide food

Applies to: enalapril / hydrochlorothiazide

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.

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