Spironolactone Disease Interactions
There are 7 disease interactions with spironolactone.
Potassium-sparing diuretics (applies to spironolactone) acidosis
Major Potential Hazard, High plausibility. Applicable conditions: Diabetes Mellitus, Pulmonary Impairment
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.
References
- Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
- "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
- Ochs HR, Greenblatt DJ, Bodem G, Smith TW "Spironolactone." Am Heart J 96 (1978): 389-400
- Gabow PA, Moore S, Schrier RW "Spironolactone-induced hyperchloremic acidosis in cirrhosis." Ann Intern Med 90 (1979): 338-40
- Feinfeld DA, Carvounis CP "Fatal hyperkalemia and hyperchloremic acidosis. Association with spironolactone in the absence of renal impairment." JAMA 240 (1978): 1516
- Jariwalla AG, Jones CR, Lever A, Hall R "Spironolactone and diabetic ketoacidosis." Postgrad Med J 57 (1981): 573-4
- "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
- "Product Information. Aldactone (spironolactone)." Searle (2001):
Potassium-sparing diuretics (applies to spironolactone) diabetes
Major Potential Hazard, High plausibility. Applicable conditions: Diabetes Mellitus
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.
References
- Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
- 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
- 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
- Hollenberg NK, Mickiewicz C "Hyperkalemia in diabetes mellitus. Effect of a triamterene- hydrochlorothiazide combination." Arch Intern Med 149 (1989): 1327-30
- 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
- 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
- Walker BR, Capuzzi DM, Alexander F, Familiar RG, Hoppe RC "Hyperkalemia after triamterene in diabetic patients." Clin Pharmacol Ther 13 (1972): 643-51
- "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
- Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
- Jariwalla AG, Jones CR, Lever A, Hall R "Spironolactone and diabetic ketoacidosis." Postgrad Med J 57 (1981): 573-4
- "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
- "Product Information. Aldactone (spironolactone)." Searle (2001):
- American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
Potassium-sparing diuretics (applies to spironolactone) electrolytes/fluid
Major Potential Hazard, High plausibility. Applicable conditions: Electrolyte Abnormalities, Hyponatremia
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.
References
- Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
- Tarssanen L, Huikko M, Rossi M "Amiloride-induced hyponatremia." Acta Med Scand 208 (1980): 491-4
- 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
- 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
- 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
- Maddox RW, Arnold WS, Dewell WM "Extreme hyperkalemia associated with amiloride ." South Med J 78 (1985): 365
- 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
- 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
- Cohen AB "Hyperkalemic effects of triamterene." Ann Intern Med 65 (1966): 521-7
- Hollenberg NK, Mickiewicz C "Hyperkalemia in diabetes mellitus. Effect of a triamterene- hydrochlorothiazide combination." Arch Intern Med 149 (1989): 1327-30
- Roberts CJ, Channer KS, Bungay D "Hyponatraemia induced by a combination of hydrochlorothiazide and triamterene." Br Med J (Clin Res Ed) 288 (1984): 1962
- 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
- 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
- Walker BR, Capuzzi DM, Alexander F, Familiar RG, Hoppe RC "Hyperkalemia after triamterene in diabetic patients." Clin Pharmacol Ther 13 (1972): 643-51
- "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
- Ochs HR, Greenblatt DJ, Bodem G, Smith TW "Spironolactone." Am Heart J 96 (1978): 389-400
- Feinfeld DA, Carvounis CP "Fatal hyperkalemia and hyperchloremic acidosis. Association with spironolactone in the absence of renal impairment." JAMA 240 (1978): 1516
- Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
- Udezue EO, Harrold BP "Hyperkalaemic paralysis due to spironolactone." Postgrad Med J 56 (1980): 254-5
- Brest AN "Spironolactone in the treatment of hypertension: a review." Clin Ther 8 (1986): 568-85
- 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
- "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
- "Product Information. Aldactone (spironolactone)." Searle (2001):
- Hirschl MM, Seidler D, Laggner AN "Spironolactone-associated hyponatremic coma." Nephron 67 (1994): 503
Potassium-sparing diuretics (applies to spironolactone) hyperkalemia
Major Potential Hazard, High plausibility.
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.
References
- Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
- 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
- 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
- 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
- Maddox RW, Arnold WS, Dewell WM "Extreme hyperkalemia associated with amiloride ." South Med J 78 (1985): 365
- 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
- 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
- Cohen AB "Hyperkalemic effects of triamterene." Ann Intern Med 65 (1966): 521-7
- Hollenberg NK, Mickiewicz C "Hyperkalemia in diabetes mellitus. Effect of a triamterene- hydrochlorothiazide combination." Arch Intern Med 149 (1989): 1327-30
- 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
- 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
- Walker BR, Capuzzi DM, Alexander F, Familiar RG, Hoppe RC "Hyperkalemia after triamterene in diabetic patients." Clin Pharmacol Ther 13 (1972): 643-51
- "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
- Ochs HR, Greenblatt DJ, Bodem G, Smith TW "Spironolactone." Am Heart J 96 (1978): 389-400
- Feinfeld DA, Carvounis CP "Fatal hyperkalemia and hyperchloremic acidosis. Association with spironolactone in the absence of renal impairment." JAMA 240 (1978): 1516
- Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
- Udezue EO, Harrold BP "Hyperkalaemic paralysis due to spironolactone." Postgrad Med J 56 (1980): 254-5
- Brest AN "Spironolactone in the treatment of hypertension: a review." Clin Ther 8 (1986): 568-85
- 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
- "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
- "Product Information. Aldactone (spironolactone)." Searle (2001):
- Marcy TR, Ripley TL "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm 63 (2006): 49-58
Potassium-sparing diuretics (applies to spironolactone) liver disease
Major Potential Hazard, Moderate plausibility.
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.
References
- Karim A, Zagarella J, Hribar J, Dooley M "Spironolactone I: disposition and metabolism." Clin Pharmacol Ther 19 (1976): 158-69
- 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
- Villeneuve JP, Rocheleau F, Raymond G "Triamterene kinetics and dynamics in cirrhosis." Clin Pharmacol Ther 35 (1984): 831-7
- Mutschler E, Gilfrich HJ, Knauf H, Mohrke W, Volger KD "Pharmacokinetics of triamterene." Clin Exp Hypertens A 5 (1983): 249-69
- Dao MT, Villeneuve JP "Kinetics and dynamics of triamterene at steady-state in patients with cirrhosis." Clin Invest Med 11 (1988): 6-9
- 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
- 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
- Overdiek HW, Merkus FW "The metabolism and biopharmaceutics of spironolactone in man." Rev Drug Metab Drug Interact 5 (1987): 273-302
- "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
- "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
- "Product Information. Aldactone (spironolactone)." Searle (2001):
- Renkes P, Gaucher P, Trechot P "Spironolactone and hepatic toxicity." JAMA 273 (1995): 376-7
Potassium-sparing diuretics (applies to spironolactone) renal dysfunction
Major Potential Hazard, High plausibility.
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.
References
- Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
- 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
- Lynn KL, Bailey RR, Swainson CP, Sainsbury R, Low WI "Renal failure with potassium-sparing diuretics." N Z Med J 98 (1985): 629-33
- George CF "Amiloride handling in renal failure." Br J Clin Pharmacol 9 (1980): 94-5
- 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
- Knauf H, Reuter K, Mutschler E "Limitation on the use of amiloride in early renal failure." Eur J Clin Pharmacol 28 (1985): 61-6
- 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
- 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
- "Triamterene and the kidney." Lancet 1 (1986): 424
- 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
- "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
- Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
- Neale TJ, Lynn KL, Bailey RR "Spironolactone-associated aggravation of renal functional impairment." N Z Med J 83 (1976): 147-9
- "Product Information. Midamor (amiloride)." Merck & Co., Inc (2001):
- "Product Information. Aldactone (spironolactone)." Searle (2001):
Potassium-sparing diuretics (applies to spironolactone) hyperuricemia
Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Gout
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.
References
- "Product Information. Dyrenium (triamterene)." SmithKline Beecham (2001):
- "Product Information. Aldactone (spironolactone)." Searle (2001):
Spironolactone drug interactions
There are 361 drug interactions with spironolactone.
Spironolactone alcohol/food interactions
There is 1 alcohol/food interaction with spironolactone.
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Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
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