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Drug Interactions between eplerenone and hydrochlorothiazide / quinapril

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

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Interactions between your drugs

Moderate

hydroCHLOROthiazide quinapril

Applies to: hydrochlorothiazide / quinapril and hydrochlorothiazide / quinapril

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

quinapril eplerenone

Applies to: hydrochlorothiazide / quinapril and eplerenone

MONITOR: Coadministration of eplerenone with ACE inhibitors or angiotensin II receptor antagonists may increase the risk of hyperkalemia due to additive pharmacodynamic effects. In clinical studies of patients with hypertension, the addition of eplerenone 50 to 100 mg to ACE inhibitors and angiotensin II receptor antagonists increased mean serum potassium slightly, by about 0.09 to 0.13 mEq/L. However, the concomitant use of another mineralocorticoid receptor blocker with these agents has led to clinically relevant hyperkalemia. In a study of diabetics with microalbuminuria, the combination of eplerenone 200 mg and enalapril 10 mg resulted in increased frequency of hyperkalemia (i.e., serum potassium greater than 5.5 mEq/L) compared to enalapril alone (38% vs. 17%). In a study of eplerenone 25 to 50 mg for the treatment of congestive heart failure postmyocardial infarction, maximum potassium levels exceeding 5.5 mEq/L were observed at a similar rate in the 90% of patients who also received ACE inhibitors or angiotensin II receptor antagonists compared to the patients who didn't.

MANAGEMENT: Given the potential for serious, sometimes fatal cardiac arrhythmias associated with hyperkalemia, caution is advised if eplerenone is administered with ACE inhibitors or angiotensin II receptor antagonists. Periodic monitoring of serum potassium levels is recommended until the effect of eplerenone is established. In clinical trials, monitoring occurred every 2 weeks for the first 1 to 2 months, then monthly thereafter. Particular caution is warranted in patients with renal impairment, diabetes, old age, or dehydration. Patients should be advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as nausea, vomiting, weakness, listlessness, tingling of the extremities, paralysis, confusion, weak pulse, and a slow or irregular heartbeat.

References

  1. (2002) "Product Information. Inspra (eplerenone)." Searle
  2. Marcy TR, Ripley TL (2006) "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm, 63, p. 49-58

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Drug and food interactions

Major

eplerenone food

Applies to: eplerenone

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of eplerenone. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In drug interaction studies, administration of a single 100 mg dose of eplerenone in combination with grapefruit juice resulted in a 25% increase in eplerenone systemic exposure (AUC). High blood levels of eplerenone can increase the risk of side effects including hyperkalemia. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with eplerenone.

References

  1. (2002) "Product Information. Inspra (eplerenone)." Searle
  2. (2021) "Product Information. Eplerenone (eplerenone)." MSN Laboratories Europe Ltd
  3. (2023) "Product Information. Eplerenone (Apotex) (eplerenone)." Apotex Pty Ltd

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Moderate

quinapril food

Applies to: hydrochlorothiazide / quinapril

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

hydroCHLOROthiazide food

Applies to: hydrochlorothiazide / quinapril

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

quinapril food

Applies to: hydrochlorothiazide / quinapril

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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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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