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Hydrochlorothiazide / spironolactone Disease Interactions

There are 18 disease interactions with hydrochlorothiazide / spironolactone:

Major

Potassium-Sparing Diuretics (Includes Hydrochlorothiazide/spironolactone) ↔ Acidosis

Severe Potential Hazard, High plausibility

Applies to: Diabetes Mellitus, Acidosis, 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

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

Potassium-Sparing Diuretics (Includes Hydrochlorothiazide/spironolactone) ↔ Diabetes

Severe Potential Hazard, High plausibility

Applies to: 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

  1. Walker BR, Capuzzi DM, Alexander F, Familiar RG, Hoppe RC "Hyperkalemia after triamterene in diabetic patients." Clin Pharmacol Ther 13 (1972): 643-51
  2. Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
  3. 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
  4. "Product Information. Aldactone (spironolactone)." Searle, Skokie, IL.
  5. "Product Information. Dyrenium (triamterene)." SmithKline Beecham, Philadelphia, PA.
  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. 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
  8. Jariwalla AG, Jones CR, Lever A, Hall R "Spironolactone and diabetic ketoacidosis." Postgrad Med J 57 (1981): 573-4
  9. Hollenberg NK, Mickiewicz C "Hyperkalemia in diabetes mellitus. Effect of a triamterene- hydrochlorothiazide combination." Arch Intern Med 149 (1989): 1327-30
  10. "Product Information. Midamor (amiloride)." Merck & Co, Inc, West Point, PA.
  11. Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
  12. 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
  13. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
View all 13 references
Major

Potassium-Sparing Diuretics (Includes Hydrochlorothiazide/spironolactone) ↔ Electrolytes/Fluid

Severe Potential Hazard, High plausibility

Applies to: 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

  1. Maddox RW, Arnold WS, Dewell WM "Extreme hyperkalemia associated with amiloride ." South Med J 78 (1985): 365
  2. Feinfeld DA, Carvounis CP "Fatal hyperkalemia and hyperchloremic acidosis. Association with spironolactone in the absence of renal impairment." JAMA 240 (1978): 1516
  3. 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
  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. Tarssanen L, Huikko M, Rossi M "Amiloride-induced hyponatremia." Acta Med Scand 208 (1980): 491-4
  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. Hollenberg NK, Mickiewicz C "Hyperkalemia in diabetes mellitus. Effect of a triamterene- hydrochlorothiazide combination." Arch Intern Med 149 (1989): 1327-30
  8. 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
  9. "Product Information. Aldactone (spironolactone)." Searle, Skokie, IL.
  10. Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
  11. Walker BR, Capuzzi DM, Alexander F, Familiar RG, Hoppe RC "Hyperkalemia after triamterene in diabetic patients." Clin Pharmacol Ther 13 (1972): 643-51
  12. Cohen AB "Hyperkalemic effects of triamterene." Ann Intern Med 65 (1966): 521-7
  13. 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
  14. Brest AN "Spironolactone in the treatment of hypertension: a review." Clin Ther 8 (1986): 568-85
  15. "Product Information. Dyrenium (triamterene)." SmithKline Beecham, Philadelphia, PA.
  16. "Product Information. Midamor (amiloride)." Merck & Co, Inc, West Point, PA.
  17. Roberts CJ, Channer KS, Bungay D "Hyponatraemia induced by a combination of hydrochlorothiazide and triamterene." Br Med J (Clin Res Ed) 288 (1984): 1962
  18. 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
  19. 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
  20. Udezue EO, Harrold BP "Hyperkalaemic paralysis due to spironolactone." Postgrad Med J 56 (1980): 254-5
  21. 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
  22. Hirschl MM, Seidler D, Laggner AN "Spironolactone-associated hyponatremic coma." Nephron 67 (1994): 503
  23. Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
  24. Ochs HR, Greenblatt DJ, Bodem G, Smith TW "Spironolactone." Am Heart J 96 (1978): 389-400
View all 24 references
Major

Potassium-Sparing Diuretics (Includes Hydrochlorothiazide/spironolactone) ↔ Hyperkalemia

Severe Potential Hazard, High plausibility

Applies to: Hyperkalemia

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

  1. Ochs HR, Greenblatt DJ, Bodem G, Smith TW "Spironolactone." Am Heart J 96 (1978): 389-400
  2. Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
  3. Brest AN "Spironolactone in the treatment of hypertension: a review." Clin Ther 8 (1986): 568-85
  4. 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
  5. Hollenberg NK, Mickiewicz C "Hyperkalemia in diabetes mellitus. Effect of a triamterene- hydrochlorothiazide combination." Arch Intern Med 149 (1989): 1327-30
  6. 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
  7. Udezue EO, Harrold BP "Hyperkalaemic paralysis due to spironolactone." Postgrad Med J 56 (1980): 254-5
  8. Cohen AB "Hyperkalemic effects of triamterene." Ann Intern Med 65 (1966): 521-7
  9. "Product Information. Midamor (amiloride)." Merck & Co, Inc, West Point, PA.
  10. 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
  11. 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
  12. Feinfeld DA, Carvounis CP "Fatal hyperkalemia and hyperchloremic acidosis. Association with spironolactone in the absence of renal impairment." JAMA 240 (1978): 1516
  13. 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
  14. Maddox RW, Arnold WS, Dewell WM "Extreme hyperkalemia associated with amiloride ." South Med J 78 (1985): 365
  15. "Product Information. Aldactone (spironolactone)." Searle, Skokie, IL.
  16. 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
  17. 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
  18. Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
  19. Walker BR, Capuzzi DM, Alexander F, Familiar RG, Hoppe RC "Hyperkalemia after triamterene in diabetic patients." Clin Pharmacol Ther 13 (1972): 643-51
  20. 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
  21. "Product Information. Dyrenium (triamterene)." SmithKline Beecham, Philadelphia, PA.
View all 21 references
Major

Potassium-Sparing Diuretics (Includes Hydrochlorothiazide/spironolactone) ↔ Liver Disease

Severe Potential Hazard, Moderate plausibility

Applies to: Liver Disease

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

  1. 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
  2. Karim A, Zagarella J, Hribar J, Dooley M "Spironolactone I: disposition and metabolism." Clin Pharmacol Ther 19 (1976): 158-69
  3. "Product Information. Midamor (amiloride)." Merck & Co, Inc, West Point, PA.
  4. Mutschler E, Gilfrich HJ, Knauf H, Mohrke W, Volger KD "Pharmacokinetics of triamterene." Clin Exp Hypertens A 5 (1983): 249-69
  5. 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
  6. Dao MT, Villeneuve JP "Kinetics and dynamics of triamterene at steady-state in patients with cirrhosis." Clin Invest Med 11 (1988): 6-9
  7. "Product Information. Aldactone (spironolactone)." Searle, Skokie, IL.
  8. Overdiek HW, Merkus FW "The metabolism and biopharmaceutics of spironolactone in man." Rev Drug Metab Drug Interact 5 (1987): 273-302
  9. "Product Information. Dyrenium (triamterene)." SmithKline Beecham, Philadelphia, PA.
  10. 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
  11. Renkes P, Gaucher P, Trechot P "Spironolactone and hepatic toxicity." JAMA 273 (1995): 376-7
  12. Villeneuve JP, Rocheleau F, Raymond G "Triamterene kinetics and dynamics in cirrhosis." Clin Pharmacol Ther 35 (1984): 831-7
View all 12 references
Major

Potassium-Sparing Diuretics (Includes Hydrochlorothiazide/spironolactone) ↔ Renal Dysfunction

Severe Potential Hazard, High plausibility

Applies to: Renal Dysfunction

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

  1. 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
  2. Knauf H, Reuter K, Mutschler E "Limitation on the use of amiloride in early renal failure." Eur J Clin Pharmacol 28 (1985): 61-6
  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. Neale TJ, Lynn KL, Bailey RR "Spironolactone-associated aggravation of renal functional impairment." N Z Med J 83 (1976): 147-9
  5. 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
  6. "Product Information. Aldactone (spironolactone)." Searle, Skokie, IL.
  7. Vidt DG "Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic." Pharmacotherapy 1 (1981): 179-86
  8. George CF "Amiloride handling in renal failure." Br J Clin Pharmacol 9 (1980): 94-5
  9. "Triamterene and the kidney." Lancet 1 (1986): 424
  10. Yap V, Patel A, Thomsen J "Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia." JAMA 236 (1976): 2775-6
  11. 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
  12. "Product Information. Dyrenium (triamterene)." SmithKline Beecham, Philadelphia, PA.
  13. 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
  14. Lynn KL, Bailey RR, Swainson CP, Sainsbury R, Low WI "Renal failure with potassium-sparing diuretics." N Z Med J 98 (1985): 629-33
  15. "Product Information. Midamor (amiloride)." Merck & Co, Inc, West Point, PA.
View all 15 references
Major

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Anuria

Severe Potential Hazard, High plausibility

Applies to: Anuria

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

References

  1. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  2. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.
  3. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  4. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical, Abbott Park, IL.
  5. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.
  6. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  7. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
  8. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  9. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.
View all 9 references
Major

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Electrolyte Losses

Severe Potential Hazard, High plausibility

Applies to: Hypokalemia, Diarrhea, Electrolyte Abnormalities, Hyperaldosteronism, Hyponatremia, Magnesium Imbalance, Malnourished, Vomiting, Ventricular Arrhythmia, Dehydration

The use of thiazide diuretics is commonly associated with loss of electrolytes, most significantly potassium but also sodium, chloride, bicarbonate, and magnesium. The loss of other electrolytes such as phosphate, bromide and iodide is usually slight. 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. Therapy with thiazide 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 prior to 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 development of hypokalemia may be particularly dangerous in these patients. The risk of hypokalemia may be minimized by slow diuresis, a lower thiazide dosage, potassium supplementation, or combined use with a potassium-sparing diuretic.

References

  1. Bain PG, Egner W, Walker PR "Thiazide-induced dilutional hyponatraemia masquerading as subarachnoid haemorrhage ." Lancet 2 (1986): 634
  2. Hollifield JW, Slaton PE "Thiazide diuretics, hypokalemia and cardiac arrhythmias." Acta Med Scand Suppl 647 (1981): 67-73
  3. Mroczek WJ "Indapamide: clinical pharmacology, therapeutic efficacy in hypertension, and adverse effects." Pharmacotherapy 3 (1983): 61-7
  4. Brors O, Jacobsen S, Foss OP, Aakvaag A "Effect of repeated doses of hydroflumethiazide on renal excretion of electrolytes and uric acid in healthy subjects." Acta Pharmacol Toxicol (Copenh) 48 (1981): 145-50
  5. Starr JM, Whalley LJ "Hypertensive Old People in Edinburgh (HOPE) Study: electrocardiographic changes after captopril or bendrofluazide treatment." Age Ageing 22 (1993): 343-8
  6. Peters RW, Hamilton J, Hamilton BP "Incidence of cardiac arrhythmias associated with mild hypokalemia induced by low-dose diuretic therapy for hypertension." South Med J 82 (1989): 966-9,
  7. Jorgensen FS, Brunner S "The long-term effect of bendroflumethiazide on renal calcium and magnesium excretion and stone formation in patients with recurring renal stones." Scand J Urol Nephrol 8 (1974): 128-31
  8. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  9. Medical Research Council Working Party on Mild to Moderate Hypertension. "Ventricular extrasystoles during thiazide treatment: substudy of MRC mild hypertension trial." Br Med J (Clin Res Ed) 287 (1983): 1249-53
  10. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  11. Ljunghall S, Backman U, Danielson BG, Fellstrom B, Johansson G, Wikstrom B "Calcium and magnesium metabolism during long-term treatment with thiazides." Scand J Urol Nephrol 15 (1981): 257-62
  12. Pinnock CA "Hyponatraemia associated with hydrochlorothiazide treatment ." Br Med J 1 (1978): 48
  13. Husby S, Marthedal NJ "Hyponatraemia due to a thiazide diuretic. A case report." Acta Med Scand 210 (1981): 523-4
  14. Oh SJ, Douglas JE, Brown RA "Hypokalemic vacuolar myopathy associated with chlorthalidone treatment." JAMA 216 (1971): 1858-9
  15. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.
  16. Gudbrandsson T, Hansson L "Combination therapy with saluretics and atenolol in essential hypertension. Effects on blood pressure, electrolytes and uric acid." Acta Med Scand Suppl 625 (1979): 86-91
  17. Gould L, Reddy CV, Zen B, Singh BK "Life-threatening reaction to thiazides." N Y State J Med 80 (1980): 1975-6
  18. Landmann-Suter R, Struyvenberg A "Initial potassium loss and hypokalaemia during chlorthalidone administration in patients with essential hypertension: the influence of dietary sodium restriction." Eur J Clin Invest 8 (1978): 155-64
  19. el-Meheiry MM, Nabih AE, Soliman MD "A clinical study of a new diuretic, Trichlormethiazide." J Trop Med Hyg 69 (1966): 209-14
  20. Brater DC "Drug therapy: Diuretic therapy." N Engl J Med 339 (1998): 387-95
  21. Sumiye L, Vivian AS, Frisof KB, Podany EC "Potassium loss associated with hydrochlorothiazide versus chlorthalidone." Clin Ther 4 (1981): 308-20
  22. Black W, Shiner P, Roman J "Severe electrolyte disturbances associated with metolazone and furosemide." South Med J 71 (1978): 381
  23. Navarro RP, O'Brien DK, Nuffort P, Spencer DL "Diuretic induced hypokalemia in the elderly." J Fam Pract 14 (1982): 685-9
  24. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.
  25. Kuller L, Farrier N, Caggiula A, Borhani N, Dunkle S "Relationship of diuretic therapy and serum magnesium levels among participants in the Multiple Risk Factor Intervention Trial." Am J Epidemiol 122 (1985): 1045-59
  26. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
  27. Lindy S, Tarssanen L "Serum calcium and phosphorus in patients treated with thiazides and furosemide." Acta Med Scand 194 (1973): 319-22
  28. Freis ED "The efficacy and safety of diuretics in treating hypertension." Ann Intern Med 122 (1995): 223-6
  29. Berglund G, Andersson O, Larsson O, Wilhelmsen L "Antihypertensive effect and side-effects of bendroflumethiazide and propranolol." Acta Med Scand 199 (1976): 499-506
  30. Elmfeldt D, Berglund G, Wedel H, Wilhelmsen L "Incidence and importance of metabolic side-effects during antihypertensive therapy." Acta Med Scand Suppl 672 (1983): 79-83
  31. Polanska AI, Baron DN "Hyponatraemia associated with hydrochlorothiazide treatment ." Br Med J 1 (1978): 175-6
  32. Holland OB, Kuhnert L, Pollard J, Padia M, Anderson RJ, Blomqvist G "Ventricular ectopic activity with diuretic therapy." Am J Hypertens 1 (1988): 380-5
  33. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical, Abbott Park, IL.
  34. Hesp R, Wilkinson PR "Potassium supplementation of thiazide therapy." Lancet 2 (1976): 1144
  35. Slotkoff L "Clinical efficacy and safety of indapamide in the treatment of edema." Am Heart J 106 (1983): 233-7
  36. Condon JR, Nassim R "Hypophosphataemia and hypokalaemia." Br Med J 1 (1970): 110
  37. Mozes B, Pines A, Werner D, Olchovsky D, Lieberman P, Frankl O "Thiazide-induced hyponatremia: an unusual neurologic course." South Med J 79 (1986): 629-31
  38. Berg KJ, Gisholt K, Wideroe TE "Potassium deficiency in hypertensives treated with diuretics. Analysis of three alternative treatments by an oral test for potassium deficiency." Eur J Clin Pharmacol 7 (1974): 401-5
  39. Fichman MP, Vorherr H, Kleeman CR, Telfer N "Diuretic-induced hyponatremia." Ann Intern Med 75 (1971): 853-63
  40. Moore TD, Bechtel TP "Hyponatremia secondary to tolbutamide and chlorothiazide." Am J Hosp Pharm 36 (1979): 1107-10
  41. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  42. Petri M, Cumber P, Grimes L, Treby D, Bryant R, Rawlins D, Ising H "The metabolic effects of thiazide therapy in the elderly: a population study." Age Ageing 15 (1986): 151-5
  43. Kuller LH, Hulley SB, Cohen JD, Neaton J "Unexpected effects of treating hypertension in men with electrocardiographic abnormalities: a critical analysis." Circulation 73 (1986): 114-23
  44. Lee MR, Morgan DB "Familial hyperkalaemia responsive to benzothiadiazine diuretic." Lancet 1 (1980): 879
  45. Mouallem M, Friedman E, Shemesh Y, Mayan H, Pauzner R, Farfel Z "Cardiac conduction defects associated with hyponatremia." Clin Cardiol 14 (1991): 165-8
  46. Benfield GF, Haffner C, Harris P, Stableforth DE "Dilutional hyponatraemia masquerading as subarachnoid haemorrhage in patient on hydrochlorothiazide/amiloride/timolol combined drug ." Lancet 2 (1986): 341
  47. Chan TY "Indapamide-induced severe hyponatremia and hypokalemia." Ann Pharmacother 29 (1995): 1124-8
  48. Stern A "Metolazone, a diuretic agent." Am Heart J 91 (1976): 262-3
  49. Brors O, Enger E, Jacobsen S, Aakvaag A, Foss OP "Effects of hydroflumethiazide in congestive heart failure: renal electrolyte excretion related to urinary thiazide excretion and aldosterone." Acta Pharmacol Toxicol (Copenh) 49 (1981): 399-406
  50. Jensen OB, Mosdal C, Reske-Nielsen E "Hypokalemic myopathy during treatment with diuretics." Acta Neurol Scand 55 (1977): 465-82
  51. Seelig CB "Magnesium deficiency in two hypertensive patient groups." South Med J 83 (1990): 739-42
  52. Struthers AD, Whitesmith R, Reid JL "Prior thiazide diuretic treatment increases adrenaline-induced hypokalaemia." Lancet 1 (1983): 1358-61
  53. Itescu S, Haskell LP, Tannenberg AM "Thiazide-induced clinically significant hypophosphatemia ." Clin Nephrol 27 (1987): 161-2
  54. Krishna GG, Narins RG "Hemodynamic consequences of diuretic-induced hypokalemia." Am J Kidney Dis 12 (1988): 329-31
  55. Stewart DE, Ikram H, Espiner EA, Nicholls MG "Arrhythmogenic potential of diuretic induced hypokalaemia in patients with mild hypertension and ischaemic heart disease." Br Heart J 54 (1985): 290-7
  56. Winchester JF, Kellett RJ, Boddy K, Boyle P, Dargie HJ, Mahaffey ME, Ward DM, Kennedy AC "Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations." Clin Pharmacol Ther 28 (1980): 611-8
  57. Ghose RR "Letter: Hyponatraemia and diuretics." Lancet 1 (1975): 578-9
  58. Papademetriou V, Fletcher R, Khatri IM, Freis ED "Diuretic-induced hypokalemia in uncomplicated systemic hypertension: effect of plasma potassium correction on cardiac arrhythmias." Am J Cardiol 52 (1983): 1017-22
  59. Simunic M, Rumboldt Z, Ljutic D, Sardelic S "Ramipril decreases chlorthalidone-induced loss of magnesium and potassium in hypertensive patients." J Clin Pharmacol 35 (1995): 1150-5
  60. Katz FH, Eckert RC, Gebott MD "Hypokalemia caused by surreptitious self-administration of diuretics." Ann Intern Med 76 (1972): 85-90
  61. Chowdhury FR, Bleicher SJ "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res 2 (1970): 13-6
  62. Papademetriou V, Price M, Notargiacomo A, Gottdiener J, Fletcher RD, Freis ED "Effect of diuretic therapy on ventricular arrhythmias in hypertensive patients with or without left ventricular hypertrophy." Am Heart J 110 (1985): 595-9
  63. Falch DK, Schreiner AM "Changes in urinary electrolytes versus serum electrolytes during treatment of primary hypertension with chlorthalidone alone and in combination with spironolactone." Acta Med Scand 209 (1981): 111-4
  64. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  65. Toner JM, Ramsay LE "Thiazide-induced hypokalaemia; prevalence higher in women." Br J Clin Pharmacol 18 (1984): 449-52
  66. Cembrowski GS, Huntington RW, 3d "Probable fatal cardiac dysrhythmia secondary to diuretic-induced hypokalemia." Am J Forensic Med Pathol 2 (1981): 243-8
  67. Byatt CM, Millard PH, Levin GE "Diuretics and electrolyte disturbances in 1000 consecutive geriatric admissions." J R Soc Med 83 (1990): 704-8
  68. Remenchik AP, Johnston LC "Potassium depletion produced by administration of chlorthalidone to nonedematous patients with arterial hypertensin." Am J Med Sci 252 (1966): 171-6
  69. Ragnarsson J, Hardarson T, Snorrason SP "Ventricular dysrhythmias in middle-aged hypertensive men treated either with a diuretic agent or a beta-blocker." Acta Med Scand 221 (1987): 143-8
  70. Read SJ, Trenerry HM, Whiting GF "Hyponatraemia and raised creatine kinase level associated with indapamide." Med J Aust 161 (1994): 607-8
  71. Kone B, Gimenez L, Watson AJ "Thiazide-induced hyponatremia." South Med J 79 (1986): 1456-7
  72. Leigh H "Letter: Factitious hypokalemia." Ann Intern Med 80 (1974): 111-2
  73. Beling S, Vukovich RA, Neiss ES, Zisblatt M, Webb E, Losi M "Long-term experience with indapamide." Am Heart J 106 (1983): 258-62
  74. Kaur J, Wahi PL "Polythiazide as a diuretic. A clinical trial." J Indian Med Assoc 48 (1967): 13-7
  75. Papademetriou V, Fletcher R, Khatri IM, Freis ED "Diuretic-induced hypokalemia in uncomplicated systemic hypertension: effect of plasma potassium correction on cardiac arrhythmias." Am J Cardiol 52 (1983): 1017-22
  76. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.
  77. Carney SL, Morgan TO "Diuretic-induced hypokalemia and altered renal function." Int J Clin Pharmacol Ther Toxicol 24 (1986): 665-7
View all 77 references
Major

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Liver Disease

Severe Potential Hazard, High plausibility

Applies to: Liver Disease

Patients with severe liver disease or cirrhosis are very susceptible to thiazide-induced hypokalemic hypochloremic alkalosis. Blood ammonia concentrations may be further increased in patients with previously elevated concentrations. Hepatic encephalopathy and death have occurred secondary to the electrolyte alterations accompanying diuretic use. Therapy with thiazide diuretics should be administered cautiously in patients with impaired hepatic function or progressive liver disease, and discontinued promptly if signs of impending hepatic coma appear (e.g., tremors, confusion, and increased jaundice).

References

  1. Sherlock S, Senewiratne B, Scott A, Walker JG "Complications of diuretic therapy in hepatic cirrhosis." Lancet 1 (1966): 1049-52
  2. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.
  3. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  4. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  5. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical, Abbott Park, IL.
  6. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  7. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.
  8. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.
  9. Sherlock S, Walker JG, Senewiratne B, Scott A "The complications of diuretic therapy in patients with cirrhosis." Ann N Y Acad Sci 139 (1966): 497-505
  10. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
  11. Aneckstein AG, Weingold AB "Chlorothiazide-induced hepatic coma in pregnancy." Am J Obstet Gynecol 95 (1966): 136-7
  12. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
View all 12 references
Major

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Lupus Erythematosus

Severe Potential Hazard, Moderate plausibility

Applies to: Lupus Erythematosus

The use of thiazide diuretics has been reported to possibly exacerbate or activate systemic lupus erythematosus. Reported cases have generally been associated with chlorothiazide and hydrochlorothiazide. Therapy with thiazide diuretics should be administered cautiously in patients with a history or risk of SLE.

References

  1. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.
  2. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.
  3. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  4. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
  5. Rich MW, Eckman JM "Can hydrochlorothiazide cause lupus?" J Rheumatol 22 (1995): 1001
  6. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  7. Parodi A, Romagnoli M, Rebora A "Subacute cutaneous lupus erythematosus-like eruption caused by hydrochlorothiazide." Photodermatol 6 (1989): 100-2
  8. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  9. Reed BR, Huff JC, Jones SK, Orton PW, Lee LA, Norris DA "Subacute cutaneous lupus erythematosus associated with hydrochlorothiazide therapy." Ann Intern Med 103 (1985): 49-51
  10. Goodrich AL, Kohn SR "Hydrochlorothiazide-induced lupus erythematosus: a new variant?" J Am Acad Dermatol 28 (1993): 1001-2
  11. Brown CW, Deng JS "Thiazide diuretics induce cutaneous lupus-like adverse reaction." J Toxicol Clin Toxicol 33 (1995): 729-33
  12. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  13. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.
  14. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical, Abbott Park, IL.
View all 14 references
Major

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Renal Function Disorders

Severe Potential Hazard, High plausibility

Applies to: Renal Dysfunction

Thiazide diuretics may be ineffective when the glomerular filtration rate is low (GFR < 25 mL/min) because they are not expected to be filtered into the renal tubule, their site of action. In addition, thiazide diuretics decrease the GFR and may precipitate azotemia in renal disease. Cumulative effects may also develop because most of these drugs are excreted unchanged in the urine by glomerular filtration and active tubular secretion. Therapy with thiazide diuretics should be administered cautiously at reduced dosages in patients with renal impairment. If renal function becomes progressively worse, as indicated by rising BUN or serum creatinine levels, an interruption or discontinuation of thiazide therapy should be considered.

References

  1. Klunk LJ, Ringel S, Neiss ES "The disposition of 14C-indapamide in man." J Clin Pharmacol 23 (1983): 377-84
  2. Brennan L, Wu MJ, Laquer UJ "A multicenter study of indapamide in hypertensive patients with impaired renal function." Clin Ther 5 (1982): 121-8
  3. Craswell PW, Ezzat E, Kopstein J, Varghese Z, Moorhead JF "Use of metolazone, a new diuretic, in patients with renal disease." Nephron 12 (1974): 63-73
  4. Riess W, Dubach UC, Burckhardt D, Theobald W, Vuillard P, Zimmerli M "Pharmacokinetic studies with chlorthalidone (Hygroton) in man." Eur J Clin Pharmacol 12 (1977): 375-82
  5. el-Meheiry MM, Nabih AE, Soliman MD "A clinical study of a new diuretic, Trichlormethiazide." J Trop Med Hyg 69 (1966): 209-14
  6. Gehr TW, Sica DA, Brater DC, et al "Metolazone pharmacokinetics and pharmacodynamics in renal transplantation." Int J Clin Pharmacol Ther Toxicol 29 (1991): 116-23
  7. Magil AB "Drug-induced acute interstitial nephritis with granulomas." Hum Pathol 14 (1983): 36-41
  8. Magil AB, Ballon HS, Cameron EC, Rae A "Acute interstitial nephritis associated with thiazide diuretics. Clinical and pathologic observations in three cases." Am J Med 69 (1980): 939-43
  9. Beermann B, Groschinsky-Grind M, Lindstrom B, Wikland B "Pharmacokinetics of bendroflumenthiazide in hypertensive patients." Eur J Clin Pharmacol 13 (1978): 119-24
  10. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
  11. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical, Abbott Park, IL.
  12. Larsson GB, Langer L, Nassberger L "Thiazide-induced kidney damage with circulating antibodies against myeloperoxidase and cardiolipin." J Intern Med 233 (1993): 493-4
  13. Sketris IS, Skoutakis VA, Acchiardo SR, Meyer MC "The pharmacokinetics of trichlormethiazide in hypertensive patients with normal and compromised renal function." Eur J Clin Pharmacol 20 (1981): 453-7
  14. Hobbs DC, Twomey TM "Kinetics of polythiazide." Clin Pharmacol Ther 23 (1978): 241-6
  15. Madkour H, Gadallah M, Plante GE, Massry SG "Comparison between the effects of indapamide and hydrochlorothiazide on creatinine clearance in patients with impaired renal function and hypertension." Am J Nephrol 15 (1995): 251-5
  16. Delevett AF, Recalde M "Diuretic-induced renal colic." JAMA 225 (1973): 992
  17. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  18. Fleuren HLJ, Verwey-van Wissen C, van Rossum JM "Dose-dependent urinary excretion of chlorthalidone." Clin Pharmacol Ther 25 (1979): 806-12
  19. Acchiardo SR, Skoutakis VA "Clinical efficacy, safety, and pharmacokinetics of indapamide in renal impairment." Am Heart J 106 (1983): 237-44
  20. Niemeyer C, Hasenfub G, Wais U, et al "Pharmacokinetics of hydrochlorothiazide in relation to renal function." Eur J Clin Pharmacol 24 (1983): 661-5
  21. Beermann B, Groschinsky-Grind M, Lindstrom B "Pharmacokinetics of bendroflumethiazide." Clin Pharmacol Ther 22 (1977): 385-8
  22. Brors O, Jacobsen S "Distribution of elimination of hydroflumethiazide in man." Eur J Clin Pharmacol 16 (1979): 125-31
  23. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.
  24. Jones B, Nanra RS "Double-blind trial of antihypertensive effect of chlorothiazide in severe renal failure." Lancet 2 (1979): 1258-60
  25. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  26. Lant AF, Baba WI, Wilson GM "Localization of the site of action of oral diuretics in the human kidney." Clin Sci 33 (1967): 11-27
  27. Yakatan GJ, Smith RB, Frome EL, Doluisio JT "Pharmacokinetics of orally administered hydroflumethiazide in man." J Clin Pharmacol 17 (1977): 37-47
  28. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.
  29. Brors O, Haffner JF, Jacobsen S "Excretion of hydroflumethiazide in bile and urine of man." Eur J Clin Pharmacol 15 (1979): 287-9
  30. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  31. Read SJ, Trenerry HM, Whiting GF "Hyponatraemia and raised creatine kinase level associated with indapamide." Med J Aust 161 (1994): 607-8
  32. Seyffart, G "Drug Dosage in Renal Insufficiency." Dordrecht, The Netherlands: Kluwer Academic Publishers 1 (1991): 227-8
  33. Beermann B, Groschinsky-Grind M, Rosen A "Absorption, metabolism, and excretion of hydrochlorothiazide." Clin Pharmacol Ther 19 (1975): 531-7
  34. Newstead CG, Moore RH, Barnes AJ "Interstitial nephritis associated with indapamide." BMJ 300 (1990): 1344
  35. Carney SL, Morgan TO "Diuretic-induced hypokalemia and altered renal function." Int J Clin Pharmacol Ther Toxicol 24 (1986): 665-7
  36. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.
  37. Bennett WM, Porter GA "Efficacy and safety of metolazone in renal failure and the nephrotic syndrome." J Clin Pharmacol 13 (1973): 357-64
  38. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  39. Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):
  40. Brater DC "Drug therapy: Diuretic therapy." N Engl J Med 339 (1998): 387-95
  41. Tilstone WJ, Dargie H, Dargie EN, Morgan HG, Kennedy AC "Pharmacokinetics of metolazone in normal subjects and in patients with cardiac or renal failure." Clin Pharmacol Ther 16 (1974): 322-9
View all 41 references
Moderate

Potassium-Sparing Diuretics (Includes Hydrochlorothiazide/spironolactone) ↔ Hyperuricemia

Moderate Potential Hazard, Moderate plausibility

Applies to: 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

  1. "Product Information. Dyrenium (triamterene)." SmithKline Beecham, Philadelphia, PA.
Moderate

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Asthma

Moderate Potential Hazard, Moderate plausibility

Applies to: Asthma

Thiazide diuretics should be used with caution in patients with history of bronchial asthma as sensitivity reactions may occur.

Moderate

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Diabetes

Moderate Potential Hazard, Moderate plausibility

Applies to: Diabetes Mellitus, Abnormal Glucose Tolerance

Thiazide diuretics may cause hyperglycemia and glycosuria in patients with diabetes. They may also precipitate diabetes in prediabetic patients. These effects are usually reversible following discontinuation of the drugs. Therapy with thiazide 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 thiazide therapy, and their antidiabetic regimen adjusted accordingly.

References

  1. Nielsen S, Schmitz A, Knudsen RE, Dollerup J, Mogensen CE "Enalapril versus bendroflumethiazide in type 2 diabetes complicated by hypertension." Q J Med 87 (1994): 747-54
  2. Diamond MT "Hyperglycemic hyperosmolar coma associated with hydrochlorothiazide and pancreatitis." N Y State J Med 72 (1972): 1741-2
  3. Blayac JP, Ribes G, Buys D, Puech R, Loubatieres-Mariani MM "Effects of a new benzothiadiazine derivative, LN 5330, on insulin secretion." Arch Int Pharmacodyn Ther 253 (1981): 154-63
  4. Pickkers P, Schachter M, Hughes AD, Feher MD, Sever PS "Thiazide-induced hyperglycaemia: a role for calcium-activated potassium channels?" Diabetologia 39 (1996): 861-4
  5. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  6. Jones IG, Pickens PT "Diabetes mellitus following oral diuretics." Practitioner 199 (1967): 209-10
  7. Petri M, Cumber P, Grimes L, Treby D, Bryant R, Rawlins D, Ising H "The metabolic effects of thiazide therapy in the elderly: a population study." Age Ageing 15 (1986): 151-5
  8. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.
  9. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  10. Berglund G, Andersson O, Widgren B "Low-dose antihypertensive treatment with a thiazide diuretic is not diabetogenic. A 10-year controlled trial with bendroflumethiazide." Acta Med Scand 220 (1986): 419-24
  11. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical, Abbott Park, IL.
  12. Andersen OO, Persson I "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J 2 (1968): 798-801
  13. Berlin I "Prazosin, diuretics, and glucose intolerance." Ann Intern Med 119 (1993): 860
  14. Elmfeldt D, Berglund G, Wedel H, Wilhelmsen L "Incidence and importance of metabolic side-effects during antihypertensive therapy." Acta Med Scand Suppl 672 (1983): 79-83
  15. Pollare T, Lithell H, Berne C "A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension." N Engl J Med 321 (1989): 868-73
  16. Chowdhury FR, Bleicher SJ "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res 2 (1970): 13-6
  17. Bell DS "Insulin resistance. An often unrecognized problem accompanying chronic medical disorders." Postgrad Med 93 (1993): 99-103,
  18. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.
  19. Slotkoff L "Clinical efficacy and safety of indapamide in the treatment of edema." Am Heart J 106 (1983): 233-7
  20. Goldman JA, Neri A, Ovadia J, Eckerling B, Vries A, de "Effect of chlorothiazide on intravenous glucose tolerance in pregnancy." Am J Obstet Gynecol 105 (1969): 556-60
  21. Freis ED "The efficacy and safety of diuretics in treating hypertension." Ann Intern Med 122 (1995): 223-6
  22. Schmitz O, Hermansen K, Nielsen OH, Christensen CK, Arnfred J, Hansen HE, Mogensen CE, Orskov H, Beck-Nielsen H "Insulin action in insulin-dependent diabetics after short-term thiazide therapy." Diabetes Care 9 (1986): 631-6
  23. Rowe P, Mather H "Hyperosmolar non-ketotic diabetes mellitus associated with metolazone." Br Med J 291 (1985): 25-6
  24. Domenet JG "Diabetogenic effect of oral diuretics." Br Med J 3 (1968): 188
  25. Seltzer HS, Allen EW "Hyperglycemia and inhibition of insulin secretion during administration of diazoxide and trichlormethiazide in man." Diabetes 18 (1969): 19-28
  26. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  27. Winchester JF, Kellett RJ, Boddy K, Boyle P, Dargie HJ, Mahaffey ME, Ward DM, Kennedy AC "Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations." Clin Pharmacol Ther 28 (1980): 611-8
  28. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  29. Murphy MB, Kohner E, Lewis PJ, Schumer B, Dollery CT "Glucose intolerance in hypertensive patients treated with diuretics: a fourteen-year follow-up." Lancet 2 (1982): 1293-5
  30. Harper R, Ennis CN, Heaney AP, Sheridan B, Gormley M, Atkinson AB, Johnston GD, Bell PM "A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM." Diabetologia 38 (1995): 853-9
  31. Beling S, Vukovich RA, Neiss ES, Zisblatt M, Webb E, Losi M "Long-term experience with indapamide." Am Heart J 106 (1983): 258-62
  32. Curtis J, Horrigan F, Ahearn D, Varney R, Sandler SG "Chlorthalidone-induced hyperosmolar hyperglycemic nonketotic coma." JAMA 220 (1972): 1592-3
  33. Kansal PC, Buse J, Buse MG "Thiazide diuretics and control of diabetes mellitus." South Med J 62 (1969): 1372-9
  34. Miller NR, Moses H "Transient oculomotor nerve palsy. Association with thiazide-induced glucose intolerance." JAMA 240 (1978): 1887-8
  35. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
  36. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.
View all 36 references
Moderate

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Hyperlipidemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Hyperlipidemia

Thiazide diuretics may increase serum triglyceride and cholesterol levels, primarily LDL and VLDL. Whether these effects are dose-related and sustained during chronic therapy are unknown. Patients with preexisting hyperlipidemia may require closer monitoring during thiazide therapy, and adjustments made accordingly in their lipid-lowering regimen

References

  1. Ames RP "A comparison of blood lipid and blood pressure responses during the treatment of systemic hypertension with indapamide and with thiazides." Am J Cardiol 77 (1996): b12-6
  2. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
  3. Freis ED "The efficacy and safety of diuretics in treating hypertension." Ann Intern Med 122 (1995): 223-6
  4. Winchester JF, Kellett RJ, Boddy K, Boyle P, Dargie HJ, Mahaffey ME, Ward DM, Kennedy AC "Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations." Clin Pharmacol Ther 28 (1980): 611-8
  5. Slotkoff L "Clinical efficacy and safety of indapamide in the treatment of edema." Am Heart J 106 (1983): 233-7
  6. Ames RP, Hill P "Increase in serum-lipids during treatment of hypertension with chlorthalidone." Lancet 1 (1976): 721-3
  7. Smith WM "Diuretics and cholesterol elevation." JAMA 242 (1979): 1612
  8. Elmfeldt D, Berglund G, Wedel H, Wilhelmsen L "Incidence and importance of metabolic side-effects during antihypertensive therapy." Acta Med Scand Suppl 672 (1983): 79-83
  9. Pollare T, Lithell H, Berne C "A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension." N Engl J Med 321 (1989): 868-73
  10. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical, Abbott Park, IL.
  11. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.
  12. Petri M, Cumber P, Grimes L, Treby D, Bryant R, Rawlins D, Ising H "The metabolic effects of thiazide therapy in the elderly: a population study." Age Ageing 15 (1986): 151-5
  13. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  14. Luther RR, Glassman HN, Estep CB, Maurath CJ, Jordan DC "The effects of terazosin and methyclothiazide on blood pressure and serum lipids." Am Heart J 117 (1989): 842-7
  15. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.
  16. Pollare T, Lithell H, Berne C "A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension." N Engl J Med 321 (1989): 868-73
  17. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  18. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.
  19. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  20. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  21. Kasiske BL, Ma JZ, Kalil RS, Louis TA "Effects of antihypertensive therapy on serum lipids." Ann Intern Med 122 (1995): 133-41
  22. Beling S, Vukovich RA, Neiss ES, Zisblatt M, Webb E, Losi M "Long-term experience with indapamide." Am Heart J 106 (1983): 258-62
  23. Fager G, Berglund G, Bondjers G, Elmfeldt D, Lager I, Olofsson SO, Smith U, Wiklund O "Effects of anti-hypertensive therapy on serum lipoproteins. Treatment with metoprolol, propranolol and hydrochlorothiazide." Artery 11 (1983): 283-96
View all 23 references
Moderate

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Hyperparathyroidism

Moderate Potential Hazard, Moderate plausibility

Applies to: Hyperparathyroidism

Urinary calcium excretion is decreased by thiazide diuretics during chronic administration. Pathologic changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been reported during prolonged therapy. However, the common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and peptic ulceration have not been seen. Clinicians should be cognizant of these effects when prescribing or administering thiazide therapy to patients with hyperparathyroidism. These drugs should be discontinued before carrying out tests for parathyroid function.

References

  1. Lindy S, Tarssanen L "Serum calcium and phosphorus in patients treated with thiazides and furosemide." Acta Med Scand 194 (1973): 319-22
  2. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
  3. Jorgensen FS, Brunner S "The long-term effect of bendroflumethiazide on renal calcium and magnesium excretion and stone formation in patients with recurring renal stones." Scand J Urol Nephrol 8 (1974): 128-31
  4. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.
  5. Paloyan E, Farland M, Pickleman JR "Hyperparathyroidism coexisting with hypertension and prolonged thiazide administration." JAMA 210 (1969): 1243-5
  6. Gammon GD, Docherty JP "Thiazide-induced hypercalcemia in a manic-depressive patient." Am J Psychiatry 137 (1980): 1453-5
  7. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.
  8. Klimiuk PS, Davies M, Adams PH "Primary hyperparathyroidism and thiazide diuretics." Postgrad Med J 57 (1981): 80-3
  9. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  10. Itescu S, Haskell LP, Tannenberg AM "Thiazide-induced clinically significant hypophosphatemia ." Clin Nephrol 27 (1987): 161-2
  11. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  12. Parfitt AM "Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism." Ann Intern Med 77 (1972): 557-63
  13. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.
  14. Paloyan E, Farland M, Pickleman JR "Hyperparathyroidism coexisting with hypertension and prolonged thiazide administration." JAMA 210 (1969): 1243-5
  15. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  16. Ljunghall S, Backman U, Danielson BG, Fellstrom B, Johansson G, Wikstrom B "Calcium and magnesium metabolism during long-term treatment with thiazides." Scand J Urol Nephrol 15 (1981): 257-62
  17. Anderson PE, Ellis GG, Austin SM "Case report: metolazone-associated hypercalcemia and acute pancreatitis." Am J Med Sci 302 (1991): 235-7
  18. Duarte CG, Winnacker JL, Becker KL, Pace A "Thiazide-induced hypercalcemia." N Engl J Med 284 (1971): 828-30
  19. Palmer FJ "Letter: Chlorthalidone-induced hypercalcemia." JAMA 229 (1974): 267
  20. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical, Abbott Park, IL.
  21. Balizet L "Recurrent parathyroid adenoma. Association with prolonged thiazide administration." JAMA 225 (1973): 1238-9
  22. Hakim R, Tolis G, Goltzman D, Meltzer S, Friedman R "Severe hypercalcemia associated with hydrochlorothiazide and calcium carbonate therapy." Can Med Assoc J 121 (1979): 591-4
  23. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  24. Parfitt AM "Chlorothiazide-induced hypercalcemia in juvenile osteoporosis and hyperparathyroidism." N Engl J Med 281 (1969): 55-9
  25. Popovtzer MM, Subryan VL, Alfrey AC, Reeve EB, Schrier RW "The acute effect of chlorothiazide on serum-ionized calcium. Evidence for a parathyroid hormone-dependent mechanism." J Clin Invest 55 (1975): 1295-302
  26. Byatt CM, Millard PH, Levin GE "Diuretics and electrolyte disturbances in 1000 consecutive geriatric admissions." J R Soc Med 83 (1990): 704-8
  27. Hilker RR "Reversible hypercalcemia associated with prolonged thiazide administration to control hypertension." J Occup Med 12 (1970): 444-5
View all 27 references
Moderate

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Hyperuricemia

Moderate Potential Hazard, High plausibility

Applies to: Gout

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

References

  1. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.
  2. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  3. Beling S, Vukovich RA, Neiss ES, Zisblatt M, Webb E, Losi M "Long-term experience with indapamide." Am Heart J 106 (1983): 258-62
  4. Labeeuw M, Pozet N, Aissa AH, Zech PY, Sassard J, Laville M "Uric acid renal handling: spontaneous changes and influence of a thiazide alone or associated with triamterene." Int J Clin Pharmacol Ther Toxicol 26 (1988): 79-83
  5. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical, Abbott Park, IL.
  6. Gudbrandsson T, Hansson L "Combination therapy with saluretics and atenolol in essential hypertension. Effects on blood pressure, electrolytes and uric acid." Acta Med Scand Suppl 625 (1979): 86-91
  7. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
  8. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.
  9. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.
  10. Brors O, Jacobsen S, Foss OP, Aakvaag A "Effect of repeated doses of hydroflumethiazide on renal excretion of electrolytes and uric acid in healthy subjects." Acta Pharmacol Toxicol (Copenh) 48 (1981): 145-50
  11. Elmfeldt D, Berglund G, Wedel H, Wilhelmsen L "Incidence and importance of metabolic side-effects during antihypertensive therapy." Acta Med Scand Suppl 672 (1983): 79-83
  12. Lapidus PW, Guidotti FP "Gout in orthopaedic practice: review of 232 cases." Clin Orthop 28 (1963): 97-110
  13. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  14. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  15. Petri M, Cumber P, Grimes L, Treby D, Bryant R, Rawlins D, Ising H "The metabolic effects of thiazide therapy in the elderly: a population study." Age Ageing 15 (1986): 151-5
  16. Freis ED "The efficacy and safety of diuretics in treating hypertension." Ann Intern Med 122 (1995): 223-6
  17. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  18. Slotkoff L "Clinical efficacy and safety of indapamide in the treatment of edema." Am Heart J 106 (1983): 233-7
  19. Ljunghall S, Backman U, Danielson BG, Fellstrom B, Johansson G, Odlind B, Wikstrom B "Effects of bendroflumethiazide on urate metabolism during treatment of patients with renal stones." J Urol 127 (1982): 1207-10
  20. Winchester JF, Kellett RJ, Boddy K, Boyle P, Dargie HJ, Mahaffey ME, Ward DM, Kennedy AC "Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations." Clin Pharmacol Ther 28 (1980): 611-8
View all 20 references
Moderate

Thiazides (Includes Hydrochlorothiazide/spironolactone) ↔ Thyroid Function Tests

Moderate Potential Hazard, Moderate plausibility

Applies to: Thyroid Disease

Thiazide diuretics may decrease serum PBI (protein-bound iodine) levels without associated thyroid disturbance. Clinicians should be cognizant of this effect when prescribing or administering thiazide therapy to patients with thyroid disorders.

References

  1. Bech K, Skovsted L, Siersbaek-Nielsen K, Hansen JM "Influence of thiazides on thyroid parameters in man." Acta Endocrinol (Copenh) 89 (1978): 673-8
  2. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.
  3. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.
  4. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  5. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  6. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  7. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.
  8. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  9. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
  10. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical, Abbott Park, IL.
View all 10 references

hydrochlorothiazide / spironolactone drug Interactions

There are 883 drug interactions with hydrochlorothiazide / spironolactone

hydrochlorothiazide / spironolactone alcohol/food Interactions

There are 2 alcohol/food interactions with hydrochlorothiazide / spironolactone

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.
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 information available.

Do not stop taking any medications without consulting your healthcare provider.

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