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Drug Interactions between lisinopril and spironolactone

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

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Major

spironolactone lisinopril

Applies to: spironolactone and lisinopril

MONITOR CLOSELY: Concomitant use of angiotensin converting enzyme (ACE) inhibitors and potassium-sparing diuretics may increase the risk of hyperkalemia. Inhibition of ACE results in decreased aldosterone secretion, which can lead to increases in serum potassium that may be additive with that induced by potassium-sparing diuretics. The interaction may be mild in most patients with normal renal function. In a retrospective review of 127 patients treated with captopril, some of whom also received a potassium-sparing diuretic or a diuretic with a potassium supplement, no association was found between captopril use and changes in serum potassium levels. In another retrospective study, enalapril was shown to have no effect on the serum potassium of 16 patients who were taking furosemide or amiloride, and there was no difference in serum potassium levels of the group taking enalapril with diuretics compared to a similar group not taking enalapril. However, life-threatening and fatal hyperkalemia have been reported to occur within days to weeks of receiving the combination in patients with risk factors such as renal impairment, diabetes, old age, severe or worsening heart failure, and concomitant use of potassium supplements or other medications that increase serum potassium. Both ACE inhibitors alone and diuretics alone have been associated with hyperkalemia in patients with renal impairment. ACE inhibitors may also cause deterioration of renal function in patients with chronic heart failure, and the risk is increased if they are sodium-depleted or dehydrated after excessive diuresis.

MANAGEMENT: Caution is advised if ACE inhibitors are used with potassium-sparing diuretics, particularly in patients with renal impairment, diabetes, old age, worsening heart failure, and/or a risk for dehydration. Serum potassium and renal function should be checked regularly, and potassium supplementation should generally be avoided unless it is closely monitored. Patients should be given dietary counseling and advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as weakness, listlessness, confusion, tingling of the extremities, and irregular heartbeat. If spironolactone is prescribed with an ACE inhibitor, some investigators recommend that its dosage not exceed 25 mg/day.

References (41)
  1. Speirs CJ, Dollery CT, Inman WH, et al. (1988) "Postmarketing surveillance of enalapril II: investigation of the potential role of enalapril in deaths with renal failure." Br Med J, 297, p. 830-2
  2. Burnakis TG, Mioduch HJ (1984) "Combined therapy with captopril and potassium supplementation: a potential for hyperkalemia." Arch Intern Med, 144, p. 2371-2
  3. 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
  4. Warren SE, O'Connor DT (1980) "Hyperkalemia resulting from captopril administration." JAMA, 244, p. 2551-2
  5. Walmsley RN, White GH, Cain M, McCarthy PJ, Booth J (1984) "Hyperkalemia in the elderly." Clin Chem, 30, p. 1409-12
  6. McNay JL, Oran E (1970) "Possible predisposition of diabetic patients to hyperkalemia following administration of potassium-retaining diuretic, amiloride (MK 870)." Metabolism, 19, p. 58-70
  7. Johnston RT, de Bono DP, Nyman CR (1992) "Preventable sudden death in patients receiving angiotensin converting enzyme inhibitors and loop/potassium sparing diuretic combinations." Int J Cardiol, 34, p. 213-5
  8. Radley AS, Fitzpatrick RW (1987) "An evaluation of the potential interaction between enalapril and amiloride." J Clin Pharm Ther, 12, p. 319-23
  9. Ponce SP, Jennings AE, Madias NE, Harrington JT (1985) "Drug-induced hyperkalemia." Medicine (Baltimore), 64, p. 357-70
  10. Lawson DH, O'Connor PC, Jick H (1982) "Drug attributed alterations in potassium handling in congestive cardiac failure." Eur J Clin Pharmacol, 23, p. 21-5
  11. (2001) "Product Information. K-Dur (potassium chloride)." Schering Corporation
  12. Schepkens H (2001) "Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone." Am J Med, 111, p. 587
  13. Hu Y, Carpenter JP, Cheung AT (2002) "Life-threatening hyperkalemia: a complication of spironolactone for heart failure in a patient with renal insufficiency." Anesth Analg, 95, p. 39-41
  14. Obialo CI, Ofili EO, Mirza T (2002) "Hyperkalemia in congestive heart failure patients aged 63 to 85 years with subclinical renal disease." Am J Cardiol, 90, p. 663-5
  15. Bozkurt B, Agoston I, Knowlton AA (2003) "Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines." J Am Coll Cardiol, 41, p. 211-4
  16. Juurlink DN, Mamdani M, Kopp A, Laupacis A, Redelmeier DA (2003) "Drug-drug interactions among elderly patients hospitalized for drug toxicity." JAMA, 289, p. 1652-8
  17. Wrenger E, Muller R, Moesenthin M, Welte T, Frolich JC, Neumann KH (2003) "Interaction of spironolactone with ACE inhibitors or angiotensin receptor blockers: analysis of 44 cases." BMJ, 327, p. 147-9
  18. Berry C, McMurray J (2001) "Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone." Am J Med, 111, p. 587
  19. Chiu TF, Bullard MJ, Chen JC, Liaw SJ, Ng CJ (1997) "Rapid life-threatening hyperkalemia after addition of amiloride HCI/hydrochlorothiazide to angiotensin-converting enzyme inhibitor therapy." Ann Emerg Med, 30, p. 612-5
  20. Atlas SA, Case DB, Sealey JE, Laragh JH, McKinstry DN (1979) "Interruption of the renin-angiotensin system in hypertensive patients by captopril induces sustained reduction in aldosterone secretion, potassium retention and natriuresis." Hypertension, 1, p. 279-80
  21. Schepkens H, Vanholder R, Billiouw JM, Lameire N (2001) "Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases." Am J Med, 110, p. 438-41
  22. Schuna AA, Schmidt GR, Pitterle ME (1986) "Serum potassium concentrations after initiation of captopril therapy." Clin Pharm, 5, p. 920-3
  23. Bennett WM (1997) "Drug interactions and consequences of sodium restriction." Am J Clin Nutr, 65, S678-81
  24. Martin J, Mourton S, Nicholls G (2003) "Severe hyperkalaemia with prescription of potassium-retaining agents in an elderly patient." N Z Med J, 116, U542
  25. Jarman PR, Mather HM (2003) "Diabetes may be independent risk factor for hyperkalaemia." BMJ, 327, p. 812
  26. Svensson M, Gustafsson F, Galatius S, Hildebrandt PR, Atar D (2003) "Hyperkalaemia and impaired renal function in patients taking spironolactone for congestive heart failure: retrospective study." BMJ, 327, p. 1141-2
  27. (2004) "Spironolactone + ace inhibitor or sartan: risk of hyperkalaemia." Prescrire Int, 13, p. 58
  28. Juurlink DN, Mamdani MM, Lee DS, et al. (2004) "Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study." N Engl J Med, 351, p. 543-51
  29. McMurray JJ, O'Meara E (2004) "Treatment of heart failure with spironolactone--trial and tribulations." N Engl J Med, 351, p. 526-8
  30. Tamirisa KP, Aaronson KD, Koelling TM (2004) "Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure." Am Heart J, 148, p. 971-8
  31. Masoudi FA, Gross CP, Wang Y, et al. (2005) "Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States, 1998-2001." Circulation, 112, p. 39-47
  32. Marcy TR, Ripley TL (2006) "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm, 63, p. 49-58
  33. Reardon LC, Macpherson DS (1998) "Hyperkalemia in outpatients using angiotensin-converting enzyme inhibitors. How much should we worry?" Arch Intern Med, 158, p. 26-32
  34. Perazella MA (2000) "Drug-induced hyperkalemia: old culprits and new offenders." Am J Med, 109, p. 307-14
  35. Cruz CS, Cruz AA, Marcilio de Souza CA (2003) "Hyperkalaemia in congestive heart failure patients using ACE inhibitors and spironolactone." Nephrol Dial Transplant, 18, p. 1814-7
  36. Berry C, McMurray JJ (2001) "Serious adverse events experienced by patients with chronic heart failure taking spironolactone." Heart, 85, E8
  37. Lakhani M (1986) "Complete heart block induced by hyperkalaemia associated with treatment with a combination of captopril and spironolactone." Br Med J (Clin Res Ed), 293, p. 271
  38. Jarman PR, Kehely AM, Mather HM (1995) "Hyperkalaemia in diabetes: prevalence and associations." Postgrad Med J, 71, p. 551-2
  39. Perazella MA, Mahnensmith RL (1997) "Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis." J Gen Intern Med, 12, p. 646-56
  40. Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS, Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association (2001) "Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association." Circulation, 104, p. 1985-91
  41. Large DM, Carr PH, Laing I, Davies M (1984) "Hyperkalaemia in diabetes mellitus--potential hazards of coexisting hyporeninaemic hypoaldosteronism." Postgrad Med J, 60, p. 370-3

Drug and food interactions

Moderate

lisinopril food

Applies to: lisinopril

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 (3)
  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
Moderate

spironolactone food

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
Moderate

lisinopril food

Applies to: lisinopril

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

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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