Furosemide + Spironolactone interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  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.

  What to do: 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.

  8 sources

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595

• alcohol

  Moderate

  Synergy

  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.

  What to do: 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.

  8 sources

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595

Conditions

Conditions in which Furosemide + Spironolactone needs care, as documented in this source.

• Acidosis

  Major

  Acidosis alters the ratio of extracellular to intracellular potassium and may commonly lead to rapid increases in serum potassium levels. Conversely, high serum potassium concentrations may potentiate acidosis. Because of their hyperkalemic effects, therapy with potassium-sparing diuretics should be avoided in patients with metabolic or respiratory acidosis. These agents should be used cautiously in patients in whom acidosis may occur, such as patients with cardiopulmonary disease, severe respiratory disease, or poorly controlled diabetes. Acid-base balance and serum potassium levels should be monitored at regular intervals.

  8 sources

  1. Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
  2. "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
  3. Ochs HR, Greenblatt DJ, Bodem G, Smith TW "Spironolactone." Am Heart J 96 (1978): 389-400
  4. Gabow PA, Moore S, Schrier RW "Spironolactone-induced hyperchloremic acidosis in cirrhosis." Ann Intern Med 90 (1979): 338-40
  5. Feinfeld DA, Carvounis CP "Fatal hyperkalemia and hyperchloremic acidosis. Association with spironolactone in the absence of renal impairment." JAMA 240 (1978): 1516
  6. Jariwalla AG, Jones CR, Lever A, Hall R "Spironolactone and diabetic ketoacidosis." Postgrad Med J 57 (1981): 573-4
  7. "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
  8. "Product Information. Aldactone (spironolactone)." Searle (2001):

• Anuria

  Major

  The use of loop diuretics is contraindicated in patients with anuria.

  4 sources

  1. "Product Information. Bumex (bumetanide)." Roche Laboratories (2002):
  2. "Product Information. Lasix (furosemide)." sanofi-aventis (2007):
  3. "Product Information. Demadex (torsemide)." Boehringer Mannheim
  4. "Product Information. Edecrin (ethacrynic acid)." Merck & Co., Inc (2001):

• Diabetes Mellitus

  Major

  Potassium-sparing diuretics can cause hyperkalemia, which may result in life-threatening cardiac arrhythmias. Patients with diabetes mellitus, with or without nephropathy, may be particularly susceptible to the hyperkalemic effect of these drugs due to a defect in the renin-angiotensin-aldosterone axis. Therapy with potassium-sparing diuretics should be avoided, if possible, in patients with diabetes, especially uncontrolled or insulin-dependent diabetes mellitus. If these drugs are used, serum potassium levels and renal function should be monitored at regular intervals. Determination of serum electrolytes is especially important during initiation of therapy, after a dosage adjustment, and during illness that could alter renal function.

  13 sources

  1. Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
  2. Svendsen UG, Ibsen H, Rasmussen S, Leth A, Nielsen MD, Dige-Petersen H, Giese J "Effects of amiloride on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in thiazide-treated hypertensive patients." Clin Pharmacol Ther 34 (1983): 448-53
  3. McNay JL, Oran E "Possible predisposition of diabetic patients to hyperkalemia following administration of potassium-retaining diuretic, amiloride (MK 870)." Metabolism 19 (1970): 58-70
  4. Hollenberg NK, Mickiewicz C "Hyperkalemia in diabetes mellitus. Effect of a triamterene- hydrochlorothiazide combination." Arch Intern Med 149 (1989): 1327-30
  5. Amery A, Berthaux P, Bulpitt C, Deruyttere M, de Schaepdryver A, Dollery C, Fagard R, Forette F, Hellemans J, Lund-Johansen PMutsers A, Tuomilehto J "Glucose intolerance during diuretic therapy. Results of trial by the European Working Party on Hypertension in the Elderly." Lancet 1 (1978): 681-3
  6. Hollenberg NK, Mickiewicz CW "Postmarketing surveillance in 70,898 patients treated with a triamterene/hydrochlorothiazide combination (Maxzide) [published erratum appears in Am J Cardiol 1990 Aug 1;66(3):388]." Am J Cardiol 63 (1989): b37-41
  7. Walker BR, Capuzzi DM, Alexander F, Familiar RG, Hoppe RC "Hyperkalemia after triamterene in diabetic patients." Clin Pharmacol Ther 13 (1972): 643-51
  8. "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):

  Show all 13 sourcesShow fewer sources

  9. Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
  10. Jariwalla AG, Jones CR, Lever A, Hall R "Spironolactone and diabetic ketoacidosis." Postgrad Med J 57 (1981): 573-4
  11. "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
  12. "Product Information. Aldactone (spironolactone)." Searle (2001):
  13. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):

• Fibrosis

  Major

  Loop diuretic therapy should be initiated in the hospital under strict observation in patients with liver cirrhosis and ascites. Sudden alteration of fluid and electrolyte balance may precipitate hepatic encephalopathy and coma in such patients, who are also at increased risk for the development of hypokalemia. Supplemental potassium and/or concomitant use of an aldosterone antagonist or potassium-sparing agent may help prevent hypokalemia and metabolic alkalosis. Loop diuretics should be withheld in patients with hepatic coma until the condition improves.

  8 sources

  1. Ring-Larsen H "Bumetanide in the treatment of hepatic ascites. A short and long-term study." Acta Med Scand 195 (1974): 411-4
  2. "Product Information. Bumex (bumetanide)." Roche Laboratories (2002):
  3. "Product Information. Lasix (furosemide)." sanofi-aventis (2007):
  4. "Product Information. Demadex (torsemide)." Boehringer Mannheim
  5. Schwartz FD, Pillay VK, Kark RM "Ethacrynic acid: its usefulness and untoward effects." Am Heart J 79 (1970): 427-8
  6. Lieberman FL, Reynolds TB "The use of ethacrynic acid in patients with cirrhosis and ascites." Gastroenterology 49 (1965): 531-8
  7. "Product Information. Edecrin (ethacrynic acid)." Merck & Co., Inc (2001):
  8. Knauf H, Mutschler E "Liver cirrhosis with ascites: pathogenesis of resistance to diuretics and long-term efficacy and safety of torasemide." Cardiology 84 (1994): 87-98

• Hyperkalemia

  Major

  The use of potassium-sparing diuretics is contraindicated in the presence of elevated serum potassium concentrations (> 5.5 mEq/L). Potassium-sparing diuretics can cause hyperkalemia, which may result in life-threatening cardiac arrhythmias. Careful monitoring of serum potassium levels is necessary in all patients treated with potassium-sparing diuretics, especially during initiation of therapy, after dosage adjustment, and during illness that could alter renal function. The diuretic should be withdrawn immediately if hyperkalemia develops, and measures should be initiated to lower serum potassium if it exceeds 6.5 mEq/L. The combined use of a potassium-sparing diuretic with a kaliuretic diuretic (e.g., thiazides) may decrease the risk of hyperkalemia.

  22 sources

  1. Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
  2. Svendsen UG, Ibsen H, Rasmussen S, Leth A, Nielsen MD, Dige-Petersen H, Giese J "Effects of amiloride on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in thiazide-treated hypertensive patients." Clin Pharmacol Ther 34 (1983): 448-53
  3. McNay JL, Oran E "Possible predisposition of diabetic patients to hyperkalemia following administration of potassium-retaining diuretic, amiloride (MK 870)." Metabolism 19 (1970): 58-70
  4. Davidson C, Burkinshaw L, Morgan DB "The effects of potassium supplements, spironolactone or amiloride on the potassium status of patients with heart failure." Postgrad Med J 54 (1978): 405-9
  5. Maddox RW, Arnold WS, Dewell WM "Extreme hyperkalemia associated with amiloride ." South Med J 78 (1985): 365
  6. Millar JA, Fraser R, Mason P, Leckie B, Cumming AM, Robertson JI "Metabolic effects of high dose amiloride and spironolactone: a comparative study in normal subjects." Br J Clin Pharmacol 18 (1984): 369-75
  7. Schiffl H, Schollmeyer P "Clinical efficacy and safety of long-term diuretic treatment in renal parenchymal hypertension." Int J Clin Pharmacol Ther Toxicol 23 (1985): 585-8
  8. Cohen AB "Hyperkalemic effects of triamterene." Ann Intern Med 65 (1966): 521-7

  Show all 22 sourcesShow fewer sources

  9. Hollenberg NK, Mickiewicz C "Hyperkalemia in diabetes mellitus. Effect of a triamterene- hydrochlorothiazide combination." Arch Intern Med 149 (1989): 1327-30
  10. Hansen KB, Bender AD "Changes in serum potassium levels occurring in patients treated with triamterene and a triamterene-hydrochlorothiazide combination." Clin Pharmacol Ther 8 (1967): 392-9
  11. Hollenberg NK, Mickiewicz CW "Postmarketing surveillance in 70,898 patients treated with a triamterene/hydrochlorothiazide combination (Maxzide) [published erratum appears in Am J Cardiol 1990 Aug 1;66(3):388]." Am J Cardiol 63 (1989): b37-41
  12. Walker BR, Capuzzi DM, Alexander F, Familiar RG, Hoppe RC "Hyperkalemia after triamterene in diabetic patients." Clin Pharmacol Ther 13 (1972): 643-51
  13. "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
  14. Ochs HR, Greenblatt DJ, Bodem G, Smith TW "Spironolactone." Am Heart J 96 (1978): 389-400
  15. Feinfeld DA, Carvounis CP "Fatal hyperkalemia and hyperchloremic acidosis. Association with spironolactone in the absence of renal impairment." JAMA 240 (1978): 1516
  16. Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
  17. Udezue EO, Harrold BP "Hyperkalaemic paralysis due to spironolactone." Postgrad Med J 56 (1980): 254-5
  18. Brest AN "Spironolactone in the treatment of hypertension: a review." Clin Ther 8 (1986): 568-85
  19. Jeunemaitre X, Dreft-Jais C, Chatellier G, Julien J, Degoulet P, Plouin P, Menard J, Corvol P "Long-term experience of spironolactone in essential hypertension." Kidney Int 34 Suppl (1988): s14-7
  20. "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
  21. "Product Information. Aldactone (spironolactone)." Searle (2001):
  22. Marcy TR, Ripley TL "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm 63 (2006): 49-58

• Kidney Diseases

  Major

  The use of potassium-sparing diuretics is contraindicated in patients with anuria, acute or progressive renal insufficiency, or diabetic nephropathy. Potassium-sparing diuretics can cause hyperkalemia, which may result in life-threatening cardiac arrhythmias. Patients with impaired renal function may be particularly susceptible to the hyperkalemic effect of these drugs. Therapy with potassium-sparing diuretics should be administered cautiously in patients with evidence of renal function impairment (BUN > 30 mg/dL or serum creatinine > 1.5 mg/dL). If these drugs are used, serum potassium levels and renal function should be monitored at regular intervals. Determination of serum electrolytes is especially important during initiation of therapy, after a dosage adjustment, and during illness that could alter renal function.

  15 sources

  1. Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
  2. Svendsen UG, Ibsen H, Rasmussen S, Leth A, Nielsen MD, Dige-Petersen H, Giese J "Effects of amiloride on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in thiazide-treated hypertensive patients." Clin Pharmacol Ther 34 (1983): 448-53
  3. Lynn KL, Bailey RR, Swainson CP, Sainsbury R, Low WI "Renal failure with potassium-sparing diuretics." N Z Med J 98 (1985): 629-33
  4. George CF "Amiloride handling in renal failure." Br J Clin Pharmacol 9 (1980): 94-5
  5. Somogyi A, Hewson D, Muirhead M, Bochner F "Amiloride disposition in geriatric patients: importance of renal function." Br J Clin Pharmacol 29 (1990): 1-8
  6. Knauf H, Reuter K, Mutschler E "Limitation on the use of amiloride in early renal failure." Eur J Clin Pharmacol 28 (1985): 61-6
  7. Schiffl H, Schollmeyer P "Clinical efficacy and safety of long-term diuretic treatment in renal parenchymal hypertension." Int J Clin Pharmacol Ther Toxicol 23 (1985): 585-8
  8. Hollenberg NK, Mickiewicz CW "Postmarketing surveillance in 70,898 patients treated with a triamterene/hydrochlorothiazide combination (Maxzide) [published erratum appears in Am J Cardiol 1990 Aug 1;66(3):388]." Am J Cardiol 63 (1989): b37-41

  Show all 15 sourcesShow fewer sources

  9. "Triamterene and the kidney." Lancet 1 (1986): 424
  10. Roy LF, Villeneuve JP, Dumont A, Dufresne LR, Duran MA, Morin C, Jobin J "Irreversible renal failure associated with triamterene." Am J Nephrol 11 (1991): 486-8
  11. "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
  12. Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
  13. Neale TJ, Lynn KL, Bailey RR "Spironolactone-associated aggravation of renal functional impairment." N Z Med J 83 (1976): 147-9
  14. "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
  15. "Product Information. Aldactone (spironolactone)." Searle (2001):

• Kidney Diseases

  Major

  Impaired effectiveness and possible delayed excretion of loop diuretics may occur in patients with severe renal dysfunction. These individuals may require high dosages that are associated with an increased risk of electrolyte abnormalities (hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia, hypocalcemia) and ototoxicity (tinnitus, hearing loss). Therapy with loop diuretics should be administered cautiously in patients with significantly impaired renal function. Prolongation of the dosing intervals may be appropriate to prevent drug accumulation. The patient should be monitored closely for the signs and symptoms of fluid or electrolyte imbalance, including dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, or gastrointestinal disturbances such as nausea and vomiting. Excessive diuresis should be avoided as it may induce dehydration and hypovolemia, which can result in an abrupt reduction in glomerular filtration and renal blood flow. If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, or if renal function becomes progressively worse as indicated by rising BUN or serum creatinine levels, an interruption or discontinuation of therapy should be considered.

  28 sources

  1. Huang CM, Atkinson AJ, Levin M, et al. "Pharmacokinetics of furosemide in advanced renal failure." Clin Pharmacol Ther 16 (1974): 659-66
  2. Cutler RE, Forrey AW, Christopher TG, Kimpel BM "Pharmacokinetics of furosemide in normal subjects and functionally anephric patients." Clin Pharmacol Ther 15 (1974): 588-96
  3. Rose HJ, O'Malley K, Pruitt AW "Depression of renal clearance of furosemide in man by azotemia." Clin Pharmacol Ther 21 (1976): 141-6
  4. Beermann B, Dalen E, Lindstrom B "Elimination of furosemide in healthy subjects and in those with renal failure." Clin Pharmacol Ther 22 (1977): 70-8
  5. Tilstone WJ, Fine A "Furosemide kinetics in renal failure." Clin Pharmacol Ther 23 (1978): 644-50
  6. Rane A, Villeneuve JP, Stone WJ, et al. "Plasma binding and disposition of furosemide in the nephrotic syndrome and in uremia." Clin Pharmacol Ther 24 (1978): 199-207
  7. Andreasen F, Hansen HE, Mikkelsen E "Pharmacokinetics of furosemide in anephric patients and in normal subjects." Eur J Clin Pharmacol 13 (1978): 41-8
  8. Keller E, Hoppe-Seyler G, Mumm R, Schollmeyer P "Influence of hepatic cirrhosis and end-stage renal disease on pharmacokinetics and pharmacodynamics of furosemide." Eur J Clin Pharmacol 20 (1981): 27-33

  Show all 28 sourcesShow fewer sources

  9. Donatucci CF, Deshon GE, Wade CE, Hunt M "Furosemide-induced disturbances of renal function in patients undergoing TURP." Urology 35 (1990): 295-300
  10. Keller E, Hoppe-Seyler G, Schollmeyer P "Disposition and diuretic effect of furosemide in the nephrotic syndrome." Clin Pharmacol Ther 32 (1982): 442-9
  11. Ward A, Heel RC "Bumetanide: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use." Drugs 28 (1984): 426-64
  12. Menday AP, Adnitt PI, Underwood PN "Effect of long-term treatment with bumetanide/amiloride on electrolytes and renal function in elderly patients with heart failure." Curr Ther Res Clin Exp 50 (1991): 57-64
  13. Pentikainen PJ, Pasternack A, Lampainen E, Neuvonen PJ, Penttila A "Bumetanide kinetics in renal failure." Clin Pharmacol Ther 37 (1985): 582-8
  14. Marcantonio LA, Auld WH, Murdoch WR, Purohit R, Skellern GG, Howes CA "The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease." Br J Clin Pharmacol 15 (1983): 245-52
  15. Berg KJ, Tromsdal A, Wideroe TE "Diuretic action of bumetanide in advanced chronic renal insufficiency." Eur J Clin Pharmacol 9 (1976): 265-75
  16. Lowenthal DT, Dickerman D "The use of diuretics in varying degrees of renal impairment: an overview." Clin Exp Hypertens A 5 (1983): 297-307
  17. "Product Information. Bumex (bumetanide)." Roche Laboratories (2002):
  18. "Product Information. Lasix (furosemide)." sanofi-aventis (2007):
  19. "Product Information. Demadex (torsemide)." Boehringer Mannheim
  20. Matz GJ, Naunton RF "Ototoxic drugs and poor renal function." JAMA 206 (1968): 2119
  21. Pillay VK, Schwartz FD, Aimi K, Kark RM "Transient and permanent deafness following treatment with ethacrynic acid in renal failure." Lancet 1 (1969): 77-9
  22. Kaye M, Dufresne L, McDade D "Ethacrynic acid in acute renal failure." Lancet 1 (1968): 1255
  23. Sullivan RC, Freemon FR, Caranasos GJ "Complications from diuretic therapy with ethacrynic acid and furosemide." South Med J 64 (1971): 869-72
  24. Plumb VJ, James TN "Clinical hazards of powerful diuretics. Furosemide and ethacrynic acid." Mod Concepts Cardiovasc Dis 47 (1978): 91-4
  25. White SJ, Williamson K "What to watch for when you give loop diuretics." RN 42 (1979): 25-7
  26. "Product Information. Edecrin (ethacrynic acid)." Merck & Co., Inc (2001):
  27. Risler T, Schwab A, Kramer B, Braun N, Erley C "Comparative pharmacokinetics and pharmacodynamics of loop diuretics in renal failure." Cardiology 84 (1994): 155-61
  28. Russo D, Minutolo R, Andreucci VE "Role of loop diuretics in chronic renal failure." Cardiology 84 (1994): 162-70

• Liver Diseases

  Major

  Rapid alterations in fluid and electrolyte balance may precipitate hepatic coma in patients with liver disease. Hepatic encephalopathy has been associated with the use of diuretics, most frequently thiazides but also some potassium-sparing diuretics. Therapy with all diuretics should be administered cautiously in patients with severely impaired hepatic function. These patients should be monitored carefully for signs and symptoms of hepatic encephalopathy such as tremors, confusion, increased jaundice, and coma. Since spironolactone and triamterene are primarily metabolized by the liver, reduced dosages of these drugs may also be necessary in severe hepatic impairment.

  12 sources

  1. Karim A, Zagarella J, Hribar J, Dooley M "Spironolactone I: disposition and metabolism." Clin Pharmacol Ther 19 (1976): 158-69
  2. Sadee W, Schroder R, Leitner E, Dagcioglu M "Multiple dose kinetics of spironolactone and canrenoate-potassium in cardiac and hepatic failure." Eur J Clin Pharmacol 7 (1974): 195-200
  3. Villeneuve JP, Rocheleau F, Raymond G "Triamterene kinetics and dynamics in cirrhosis." Clin Pharmacol Ther 35 (1984): 831-7
  4. Mutschler E, Gilfrich HJ, Knauf H, Mohrke W, Volger KD "Pharmacokinetics of triamterene." Clin Exp Hypertens A 5 (1983): 249-69
  5. Dao MT, Villeneuve JP "Kinetics and dynamics of triamterene at steady-state in patients with cirrhosis." Clin Invest Med 11 (1988): 6-9
  6. Sungaila I, Bartle WR, Walker SE, DeAngelis C, Uetrecht J, Pappas C, Vidins E "Spironolactone pharmacokinetics and pharmacodynamics in patis with cirrhotic ascites." Gastroenterology 102 (1992): 1680-5
  7. Abshagen U, Rennekamp H, Luszpinski G "Disposition kinetics of spironolactone in hepatic failure after single doses and prolonged treatment." Eur J Clin Pharmacol 11 (1977): 169-76
  8. Overdiek HW, Merkus FW "The metabolism and biopharmaceutics of spironolactone in man." Rev Drug Metab Drug Interact 5 (1987): 273-302

  Show all 12 sourcesShow fewer sources

  9. "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
  10. "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
  11. "Product Information. Aldactone (spironolactone)." Searle (2001):
  12. Renkes P, Gaucher P, Trechot P "Spironolactone and hepatic toxicity." JAMA 273 (1995): 376-7

• Ototoxicity

  Major

  Tinnitus and hearing loss, both reversible and permanent, have been reported with the use of loop diuretics. Ototoxic effects have generally been associated with rapid intravenous or intramuscular injection, severe renal impairment, unusually high dosages (i.e. several times the usual recommended dosages), and/or concomitant use of other ototoxic agents. Therapy with loop diuretics should be administered cautiously in patients with preexisting vestibular and/or auditory impairment, since it may delay the recognition or confound the diagnosis of a drug-induced ototoxic effect. High-dose parenteral therapy should be administered as controlled infusion.

  40 sources

  1. "Product Information. Bumex (bumetanide)." Roche Laboratories (2002):
  2. "Product Information. Lasix (furosemide)." sanofi-aventis (2007):
  3. Vargish T, Benjamin R, Shenkman L "Deafness from furosemide." Ann Intern Med 72 (1970): 761
  4. Quick CA, Hoppe W "Permanent deafness associated with furosemide administration." Ann Otol Rhinol Laryngol 84 (1975): 94-101
  5. David D, Hitzig P "Diuretics and ototoxicity." N Engl J Med 284 (1971): 1328
  6. Heidland A, Wigand N "Influence of high doses of furosemide on hearing of uremic patients." Klin Wochenschr 48 (1970): 1052
  7. Lloyd-Mostyn R, Lord I "Ototoxicity of intravenous furosemide." Lancet 2 (1971): 1156
  8. Schwartz G "Ototoxicity induced by furosemide." N Engl J Med 282 (1970): 1413

  Show all 40 sourcesShow fewer sources

  9. Venkateswaran P "Transient deafness from high doses of furosemide." Br Med J 4 (1971): 113
  10. "Product Information. Demadex (torsemide)." Boehringer Mannheim
  11. Cooperman LB, Rubin IL "Toxicity of ethacrynic acid and furosemide." Am Heart J 85 (1973): 831-4
  12. Schwartz FD, Pillay VK, Kark RM "Ethacrynic acid: its usefulness and untoward effects." Am Heart J 79 (1970): 427-8
  13. Schneider WJ, Becker EL "Acute transient hearing loss after ethacrynic acid therapy." Arch Intern Med 117 (1966): 715-7
  14. Matz GJ, Beal DD, Krames L "Ototoxicity of ethacrynic acid. Demonstrated in a human temporal bone." Arch Otolaryngol 90 (1969): 152-5
  15. Rybak LP "Ototoxicity of ethacrynic acid (a persistent clinical problem)." J Laryngol Otol 102 (1988): 518-20
  16. Meriwether WD, Mangi RJ, Serpick AA "Deafness following standard intravenous dose of ethacrynic acid." JAMA 216 (1971): 795-8
  17. Merrill JP "Hazards of ethacrynic acid." JAMA 212 (1970): 159
  18. Chaffee WG Jr "Hazards of ethacrynic acid." JAMA 212 (1970): 159
  19. Matz GJ, Naunton RF "Ototoxic drugs and poor renal function." JAMA 206 (1968): 2119
  20. Pillay VK, Schwartz FD, Aimi K, Kark RM "Transient and permanent deafness following treatment with ethacrynic acid in renal failure." Lancet 1 (1969): 77-9
  21. Ng PS, Conley CE, Ing TS "Deafness after ethacrynic acid." Lancet 1 (1969): 673-4
  22. Matz GJ "The ototoxic effects of ethacrynic acid in man and animals." Laryngoscope 86 (1976): 1065-86
  23. Quick CA, Duvall AJ 3d "Early changes in the cochlear duct from ethacrynic acid: an electronmicroscopie evaluation." Laryngoscope 80 (1970): 954-65
  24. Hybels RL "Drug toxicity of the inner ear." Med Clin North Am 63 (1979): 309-19
  25. Gomolin IH, Garschick E "Ethacrynic acid-induced deafness accompanied by nystagmus." N Engl J Med 303 (1980): 702
  26. Homer MJ "Deafness after ethacrynic acid." N Engl J Med 285 (1971): 1152
  27. David DS, Hitzig P "Diuretics and ototoxicity." N Engl J Med 284 (1971): 1328-9
  28. Marlowe FI "Ototoxic agents." Otolaryngol Clin North Am 11 (1978): 791-800
  29. Rybak LP "Ototoxicity of loop diuretics." Otolaryngol Clin North Am 26 (1993): 829-44
  30. Sheffield PA, Turner JS Jr "Ototoxic drugs: a review of clinical aspects, histopathologic changes and mechanisms of action." South Med J 64 (1971): 359-63
  31. Arnold W, Nadol JB Jr, Weidauer H "Ultrastructural histopathology in a case of human ototoxicity due to loop diuretics." Acta Otolaryngol (Stockh) 91 (1981): 399-414
  32. Ballantyne J "Ototoxicity: a clinical review." Audiology 12 (1973): 325-36
  33. Beauchamp GD, Crouch TC "Deafness. Review of intravenous ethacrynic acid." J Kans Med Soc 76 (1975): 166-8,180
  34. Ajodhia JM, Dix MR "Drug-induced deafness and its treatment." Practitioner 216 (1976): 561-70
  35. Boston Collaborative Drug Surveillance Program "Drug-induced deafness." JAMA 224 (1973): 515-6
  36. "Product Information. Edecrin (ethacrynic acid)." Merck & Co., Inc (2001):
  37. Dunn CJ, Fitton A, Brogden RN "Torasemide: an update of its pharmacological properties and therapeutic efficacy." Drugs 49 (1995): 121-42
  38. Blose JS, Adams KF, Patterson JH "Torsemide: a pyridine-sulfonylurea loop diuretic." Ann Pharmacother 29 (1995): 396-402
  39. Fowler SF, Murray KM "Torsemide: a new loop diuretic." Am J Health Syst Pharm 52 (1995): 1771-80
  40. Fowler SF, Murray KM "Torsemide: a new loop diuretic." Am J Health Syst Pharm 52 (1995): 1771-80

• Water-Electrolyte Imbalance

  Major

  All diuretics may cause or aggravate fluid and electrolyte disturbances. Potassium-sparing diuretics may cause hyperkalemia and, infrequently, hyponatremia. The latter generally occurs when these agents are combined with other diuretics such as thiazides or used in markedly edematous patients with restricted sodium intake. Therapy with potassium-sparing diuretics should be administered cautiously in patients with or predisposed to electrolyte abnormalities. Electrolyte imbalances should be corrected prior to initiating therapy, and serum electrolyte concentrations should be monitored periodically and maintained at normal ranges during therapy. Determination of serum electrolytes is especially important during initiation of therapy, after a dosage adjustment, and during illness that could alter renal function.

  24 sources

  1. Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
  2. Tarssanen L, Huikko M, Rossi M "Amiloride-induced hyponatremia." Acta Med Scand 208 (1980): 491-4
  3. Svendsen UG, Ibsen H, Rasmussen S, Leth A, Nielsen MD, Dige-Petersen H, Giese J "Effects of amiloride on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in thiazide-treated hypertensive patients." Clin Pharmacol Ther 34 (1983): 448-53
  4. McNay JL, Oran E "Possible predisposition of diabetic patients to hyperkalemia following administration of potassium-retaining diuretic, amiloride (MK 870)." Metabolism 19 (1970): 58-70
  5. Davidson C, Burkinshaw L, Morgan DB "The effects of potassium supplements, spironolactone or amiloride on the potassium status of patients with heart failure." Postgrad Med J 54 (1978): 405-9
  6. Maddox RW, Arnold WS, Dewell WM "Extreme hyperkalemia associated with amiloride ." South Med J 78 (1985): 365
  7. Millar JA, Fraser R, Mason P, Leckie B, Cumming AM, Robertson JI "Metabolic effects of high dose amiloride and spironolactone: a comparative study in normal subjects." Br J Clin Pharmacol 18 (1984): 369-75
  8. Schiffl H, Schollmeyer P "Clinical efficacy and safety of long-term diuretic treatment in renal parenchymal hypertension." Int J Clin Pharmacol Ther Toxicol 23 (1985): 585-8

  Show all 24 sourcesShow fewer sources

  9. Cohen AB "Hyperkalemic effects of triamterene." Ann Intern Med 65 (1966): 521-7
  10. Hollenberg NK, Mickiewicz C "Hyperkalemia in diabetes mellitus. Effect of a triamterene- hydrochlorothiazide combination." Arch Intern Med 149 (1989): 1327-30
  11. Roberts CJ, Channer KS, Bungay D "Hyponatraemia induced by a combination of hydrochlorothiazide and triamterene." Br Med J (Clin Res Ed) 288 (1984): 1962
  12. Hansen KB, Bender AD "Changes in serum potassium levels occurring in patients treated with triamterene and a triamterene-hydrochlorothiazide combination." Clin Pharmacol Ther 8 (1967): 392-9
  13. Hollenberg NK, Mickiewicz CW "Postmarketing surveillance in 70,898 patients treated with a triamterene/hydrochlorothiazide combination (Maxzide) [published erratum appears in Am J Cardiol 1990 Aug 1;66(3):388]." Am J Cardiol 63 (1989): b37-41
  14. Walker BR, Capuzzi DM, Alexander F, Familiar RG, Hoppe RC "Hyperkalemia after triamterene in diabetic patients." Clin Pharmacol Ther 13 (1972): 643-51
  15. "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
  16. Ochs HR, Greenblatt DJ, Bodem G, Smith TW "Spironolactone." Am Heart J 96 (1978): 389-400
  17. Feinfeld DA, Carvounis CP "Fatal hyperkalemia and hyperchloremic acidosis. Association with spironolactone in the absence of renal impairment." JAMA 240 (1978): 1516
  18. Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
  19. Udezue EO, Harrold BP "Hyperkalaemic paralysis due to spironolactone." Postgrad Med J 56 (1980): 254-5
  20. Brest AN "Spironolactone in the treatment of hypertension: a review." Clin Ther 8 (1986): 568-85
  21. Jeunemaitre X, Dreft-Jais C, Chatellier G, Julien J, Degoulet P, Plouin P, Menard J, Corvol P "Long-term experience of spironolactone in essential hypertension." Kidney Int 34 Suppl (1988): s14-7
  22. "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
  23. "Product Information. Aldactone (spironolactone)." Searle (2001):
  24. Hirschl MM, Seidler D, Laggner AN "Spironolactone-associated hyponatremic coma." Nephron 67 (1994): 503

• Water-Electrolyte Imbalance

  Major

  The use of loop diuretics, particularly at high dosages or during chronic therapy, is commonly associated with loss of electrolytes, including potassium, sodium, chloride, magnesium, and calcium. Potassium and magnesium depletion may lead to cardiac arrhythmias and cardiac arrest. Other electrolyte-related complications include metabolic alkalosis and hyponatremia, which are rarely life-threatening. Excessive diuresis, as indicated by rapid weight loss, may induce dehydration and hypovolemia, which can result in acute hypotension, orthostasis, circulatory collapse, vascular thrombosis and embolism, and abrupt reduction in glomerular filtration and renal blood flow. Severe dehydration is most likely to occur in the elderly and patients under prolonged sodium restriction. Therapy with loop diuretics should be administered cautiously in patients with or predisposed to fluid and electrolyte depletion, including patients with primary or secondary aldosteronism (may have low potassium levels); those with severe or prolonged diarrhea or vomiting; and those with poor nutritional status. Fluid and electrolyte abnormalities should be corrected before initiating therapy, and blood pressure as well as serum electrolyte concentrations monitored periodically and maintained at normal ranges during therapy. Patients should be advised to immediately report signs and symptoms of fluid or electrolyte imbalance, including dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, or gastrointestinal disturbances such as nausea and vomiting. Digitalized patients and patients with a history of ventricular arrhythmias should be monitored carefully, since the development of hypokalemia may be particularly dangerous in these patients. The risk of hypokalemia may be minimized by slow diuresis, a lower diuretic dosage, potassium supplementation, or combined use with a potassium-sparing diuretic. Similarly, to prevent excessive dehydration and hyponatremia, sodium intake should be liberalized if clinically feasible.

  27 sources

  1. Tambyah JA, Lim MK "Effect of furesomide on calcium excretion." Br Med J 03/22/69 (1969): 751-2
  2. Roesner M "The loop diuretics: focus on furosemide and ethacrynic acid." N C Med J 47 (1986): 93-6
  3. Ponto LL, Schoenwald RD "Furosemide (frusemide): a pharmacokinetic/pharmacodynamic review." Clin Pharmacokinet 18 (1990): 381-408
  4. Ward A, Heel RC "Bumetanide: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use." Drugs 28 (1984): 426-64
  5. Menday AP, Adnitt PI, Underwood PN "Effect of long-term treatment with bumetanide/amiloride on electrolytes and renal function in elderly patients with heart failure." Curr Ther Res Clin Exp 50 (1991): 57-64
  6. Kubik MM, Bowers E, Underwood PN "Longterm experience of the routine use of bumetanide." Br J Clin Pract 30 (1976): 11-4
  7. "Product Information. Bumex (bumetanide)." Roche Laboratories (2002):
  8. "Product Information. Lasix (furosemide)." sanofi-aventis (2007):

  Show all 27 sourcesShow fewer sources

  9. "Product Information. Demadex (torsemide)." Boehringer Mannheim
  10. Schwartz AB "Diuretic-induced hypokalemia." Am Fam Physician 11 (1975): 101-4
  11. Cooperman LB, Rubin IL "Toxicity of ethacrynic acid and furosemide." Am Heart J 85 (1973): 831-4
  12. Schwartz FD, Pillay VK, Kark RM "Ethacrynic acid: its usefulness and untoward effects." Am Heart J 79 (1970): 427-8
  13. DeRubertis FR, Michelis MF, Beck N, Davis BB "Complications of diuretic therapy: severe alkalosis and syndrome resembling inappropriate secretion of antidiuretic hormone." Metabolism 19 (1970): 709-19
  14. Sullivan RC, Freemon FR, Caranasos GJ "Complications from diuretic therapy with ethacrynic acid and furosemide." South Med J 64 (1971): 869-72
  15. Plumb VJ, James TN "Clinical hazards of powerful diuretics. Furosemide and ethacrynic acid." Mod Concepts Cardiovasc Dis 47 (1978): 91-4
  16. Schmidt P, Friedman IS "Adverse effects of ethacrynic acid." N Y State J Med 67 (1967): 1438-42
  17. Martinez-Maldonado M "Electrolyte disturbances resulting from diuretic therapy." Tex Med 69 (1973): 83-7
  18. Gaillard R, Vallotton B, Muller F "Letter: Hypotension after angiotensin-II infusion and hypovolaemia induced by diuretic." Lancet 1 (1974): 1349
  19. White SJ, Williamson K "What to watch for when you give loop diuretics." RN 42 (1979): 25-7
  20. "Product Information. Edecrin (ethacrynic acid)." Merck & Co., Inc (2001):
  21. Patterson JH, Adams KF, Applefeld MM, Corder CN, Masse BR "Oral torsemide in patients with chronic congestive heart failure: effects on body weight, edema, and electrolyte excretion." Pharmacotherapy 14 (1994): 514-21
  22. Oberbauer R, Krivanek P, Turnheim K "Pharmacokinetics and pharmacodynamics of the diuretic bumetanide in the elderly." Clin Pharmacol Ther 57 (1995): 42-51
  23. Dunn CJ, Fitton A, Brogden RN "Torasemide: an update of its pharmacological properties and therapeutic efficacy." Drugs 49 (1995): 121-42
  24. Blose JS, Adams KF, Patterson JH "Torsemide: a pyridine-sulfonylurea loop diuretic." Ann Pharmacother 29 (1995): 396-402
  25. Fowler SF, Murray KM "Torsemide: a new loop diuretic." Am J Health Syst Pharm 52 (1995): 1771-80
  26. Fowler SF, Murray KM "Torsemide: a new loop diuretic." Am J Health Syst Pharm 52 (1995): 1771-80
  27. Palmer BF, Gates JR, Lader M "Causes and management of hyponatremia." Ann Pharmacother 37 (2003): 1694-702

• Diabetes Mellitus

  Moderate

  Loop diuretics may cause hyperglycemia, glycosuria, and alterations in glucose tolerance tests. Rarely, precipitation of diabetes mellitus has been reported. Therapy with loop diuretics should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during therapy, and their antidiabetic regimen adjusted accordingly.

  10 sources

  1. Chaudhuri ML, Catania J "A comparison of the effects of bumetanide (Burinex) and frusemide on carbohydrate metabolism in the elderly." Br J Clin Pract 42 (1988): 427-9
  2. Andersen OO, Persson I "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J 2 (1968): 798-801
  3. Gray GM "Drugs, malnutrition, and carbohydrate absorption." Am J Clin Nutr 26 (1973): 121-4
  4. "Product Information. Bumex (bumetanide)." Roche Laboratories (2002):
  5. "Product Information. Lasix (furosemide)." sanofi-aventis (2007):
  6. Dimitriadis G, Tegos C, Golfinopoulou L, Roboti C, Raptis S "Furosemide-induced hyperglycaemia - the implication of glycolytic kinases." Horm Metab Res 25 (1993): 557-9
  7. "Product Information. Demadex (torsemide)." Boehringer Mannheim
  8. Domenet JG "Diabetogenic effect of oral diuretics." Br Med J 3 (1968): 188

  Show all 10 sourcesShow fewer sources

  9. Coni NK, Gordon PW, Mukherjee AP, Read PR "The effect of frusemide and ethacrynic acid on carbohydrate metabolism." Age Ageing 3 (1974): 85-90
  10. "Product Information. Edecrin (ethacrynic acid)." Merck & Co., Inc (2001):

• Hyperuricemia

  Moderate

  Potassium-sparing diuretics have been reported to elevate serum uric acid levels. Therapy with these agents should be administered cautiously in patients with a history of gout.

  2 sources

  1. "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
  2. "Product Information. Aldactone (spironolactone)." Searle (2001):

• Hyperuricemia

  Moderate

  Loop diuretics may decrease the rate of uric acid excretion. Hyperuricemia can occur but is usually asymptomatic and rarely leads to clinical gout except in patients with a history of gout or chronic renal failure. Therapy with loop diuretics should be administered cautiously in such patients.

  4 sources

  1. "Product Information. Bumex (bumetanide)." Roche Laboratories (2002):
  2. "Product Information. Lasix (furosemide)." sanofi-aventis (2007):
  3. "Product Information. Demadex (torsemide)." Boehringer Mannheim
  4. "Product Information. Edecrin (ethacrynic acid)." Merck & Co., Inc (2001):

• Lupus Erythematosus, Systemic

  Moderate

  The use of furosemide has been associated with exacerbation or activation of systemic lupus erythematosus. Therapy with furosemide should be administered cautiously in patients with a history of lupus.

  1 source

  1. "Product Information. Lasix (furosemide)." sanofi-aventis (2007):

• Urinary Retention

  Moderate

  The use of loop diuretics can cause urinary retention in patients with bladder emptying disorders, prostate hyperplasia, narrowing of the urethra. Caution and monitoring is recommended when using loop diuretics in these patients, especially when commencing therapy.

  2 sources

  1. "Product Information. Lasix (furosemide)." sanofi-aventis (2007):
  2. "Product Information. Demadex (torsemide)." Boehringer Mannheim

Therapeutic duplication

Drug classes that overlap with Furosemide + Spironolactone, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.

• potassium sparing diuretics

  The recommended maximum number of medicines in the 'potassium sparing diuretics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'potassium sparing diuretics' category.

  Example product in the source data (US market): Rajani

• potassium sparing diuretics

  The recommended maximum number of medicines in the 'potassium sparing diuretics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'potassium sparing diuretics' category.

  Example product in the source data (US market): Hydrochlorothiazide/triamterene

• potassium sparing diuretics

  The recommended maximum number of medicines in the 'potassium sparing diuretics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'potassium sparing diuretics' category.

  Example product in the source data (US market): Moduretic 5-50

• potassium sparing diuretics

  The recommended maximum number of medicines in the 'potassium sparing diuretics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'potassium sparing diuretics' category.

  Example product in the source data (US market): Drospirenone/estradiol

• potassium sparing diuretics

  The recommended maximum number of medicines in the 'potassium sparing diuretics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'potassium sparing diuretics' category.

  Example product in the source data (US market): Nextstellis

• potassium sparing diuretics

  The recommended maximum number of medicines in the 'potassium sparing diuretics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'potassium sparing diuretics' category.

  Example product in the source data (US market): Ocella