Candesartan Cilexetil + Hydrochlorothiazide 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

• Food High in Potassium

  Moderate

  Synergy

  Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

  What to do: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

  2 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):

Conditions

Conditions in which Candesartan Cilexetil + Hydrochlorothiazide needs care, as documented in this source.

• Angioedema

  Major

  The use of these agents is contraindicated in patients with a history of angioedema related to previous angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) therapy or in patients with hereditary angioedema. Patients with a history of angioedema unrelated to these agents may be at increased risk of angioedema while receiving angiotensin II receptor (AR) antagonists. Patients should be advised to immediately report any signs or symptoms suggestive of angioedema (swelling of face, extremities, eyes, lips, or tongue, or difficulty swallowing or breathing) and to stop taking the medication until otherwise directed by their physician. Emergency therapy and/or measures to prevent airway obstruction are required for angioedema involving the tongue, glottis, or larynx. Treatment with angiotensin II receptor (AR) antagonists should be discontinued permanently if angioedema develops in association with therapy.

  8 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  4. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  5. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  6. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  7. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  8. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Anuria

  Major

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

  9 sources

  1. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  2. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):
  3. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  4. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):
  5. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):
  6. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  7. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):
  8. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):

  Show all 9 sourcesShow fewer sources

  9. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.

• Diabetes Mellitus

  Major

  The coadministration of some angiotensin II receptor blocker agents with aliskiren is contraindicated in patients with diabetes.

  7 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  4. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  5. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  6. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  7. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Hypotension

  Major

  Angiotensin II receptor (AR) antagonists can cause symptomatic hypotension in patients with an activated renin-angiotensin system, such as volume- and/or sodium-depleted patients. Therapy with AR antagonists should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if high doses were used or if recently instituted; those on dietary salt restriction; renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with AR antagonists, and the patient should be hemodynamically stable. Ideally, patients at risk for excessive hypotension should initiate AR antagonist therapy under close medical supervision, preferably with a lower dose, and followed closely for the first 2 weeks of treatment and whenever the dosage of AR antagonist or diuretic is increased.

  27 sources

  1. Goldberg MR, Bradstreet TE, McWilliams EJ, Tanaka WK, Lipert S, Bjornsson TD, Waldman SA, Osborne B, Pivadori L, Lewis G, et al. "Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients." Hypertension 25 (1995): 37-46
  2. Doig JK, MacFadyen RJ, Sweet CS, Lees KR, Reid JL "Dose-ranging study of the angiotensin type I receptor antagonist losartan (DuP753/MK954), in salt-deplete normal man." J Cardiovasc Pharmacol 21 (1993): 732-8
  3. Goldberg AI, Dunlay MC, Sweet CS "Safety and tolerability of losartan potassium, and angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension." Am J Cardiol 75 (1995): 793-5
  4. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  5. Weber MA, Bryyny RL, Pratt JH, et al. "Blood pressure effects of the angiotensin II receptor blocker, losartan." Arch Intern Med 155 (1995): 405-11
  6. Mcintyre M, Macfadyen RJ, Meredith PA, Menard J, Brunner HR, Insuasty J, Reid JL "Comparison of the oral angiotensin II receptor antagonist UP 269-6 or enalapril 20 mg on blood pressure and neurohormonal effects in salt-deplete man." J Cardiovasc Pharmacol 25 (1995): 994-1000
  7. Goldberg AI, Dunlay MC, Sweet CS "Safety and tolerability of losartan compared with atenolol, felodipine and angiotensin converting enzyme inhibitors." J Hypertens 13 Suppl (1995): s77-80
  8. Tikkanen I, Omvik P, Jensen HA "Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension." J Hypertens 13 (1995): 1343-51

  Show all 27 sourcesShow fewer sources

  9. Schaefer KL, Porter JA "Angiotensin II receptor antagonists: the prototype losartan." Ann Pharmacother 30 (1996): 625-36
  10. Weir MR, Elkins M, Liss C, Vrecenak AJ, Barr E, Edelman JM "Efficacy, tolerability, and quality of life of losartan, alone or with hydrochlorothiazide, versus nifedipine GITS in patients with essential hypertension." Clin Ther 18 (1996): 411-28
  11. Waeber B, Brunner HR "Angiotensin II antagonists: a new class of antihypertensive agent." Br J Clin Pract 50 (1996): 265-8
  12. Gibbs CR, Ferner RE, Beevers DG "Angiotensin receptor antagonists - a new class of antihypertensive drug." J Clin Pharm Ther 21 (1996): 127-30
  13. Ellis ML, Patterson H "A new class of antihypertensive therapy: angiotensin II receptor antagonists." Pharmacotherapy 16 (1996): 849-60
  14. Holwerda NJ, Fogari R, Angeli P, et al. "Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril." J Hypertens 14 (1996): 1147-115
  15. Oparil S, Barr E, Elkins M, Liss C, Vrecenak A, Edelman J "Efficacy, tolerability, and effects on quality of life of losartan, alone or with hydrochlorothiazide, versus amlodipine, alone or with hydrochlorothiazide, in patients with essential hypertension." Clin Ther 18 (1996): 608-25
  16. Waeber B, Burnier M, Nussberger J, Brunner HR "Experience with angiotensin II antagonists in hypertensive patients." Clin Exp Pharmacol Physiol 23 ( Suppl (1996): s142-6
  17. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  18. van den Meiracker AH, Admiraal PJ, Janssen JA, Kroodsma JM, de Ronde WA, Boomsma F, Sissmann J, Blankestijn PJ, Mulder PG, Man In 't Veld AJ "Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension." Hypertension 25 (1995): 22-9
  19. McIntyre M, MacFadyen RJ, Meredith PA, Brouard R, Reid JL "Dose-ranging study of the angiotensin II receptor antagonist irbesartan (SR 47436/BMS-186295) on blood pressure and neurohormona effects in salt-deplete men." J Cardiovasc Pharmacol 28 (1996): 101-6
  20. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  21. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  22. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  23. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  24. Karlberg BE, Lins LE, Hermansson K "Efficacy and safety of telmisartan, a selective AT(1) receptor antagonist, compared with enalapril in elderly patients with primary hypertension." J Hypertens 17 (1999): 293-302
  25. McClellan KJ, Markham A "Telmisartan." Drugs 56 (1998): 1039-44
  26. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  27. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Kidney Failure, Chronic

  Major

  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.

  41 sources

  1. Fleuren HLJ, Verwey-van Wissen C, van Rossum JM "Dose-dependent urinary excretion of chlorthalidone." Clin Pharmacol Ther 25 (1979): 806-12
  2. Beermann B, Groschinsky-Grind M, Rosen A "Absorption, metabolism, and excretion of hydrochlorothiazide." Clin Pharmacol Ther 19 (1975): 531-7
  3. Niemeyer C, Hasenfub G, Wais U, et al. "Pharmacokinetics of hydrochlorothiazide in relation to renal function." Eur J Clin Pharmacol 24 (1983): 661-5
  4. 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
  5. Jones B, Nanra RS "Double-blind trial of antihypertensive effect of chlorothiazide in severe renal failure." Lancet 2 (1979): 1258-60
  6. Carney SL, Morgan TO "Diuretic-induced hypokalemia and altered renal function." Int J Clin Pharmacol Ther Toxicol 24 (1986): 665-7
  7. 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
  8. Magil AB "Drug-induced acute interstitial nephritis with granulomas." Hum Pathol 14 (1983): 36-41

  Show all 41 sourcesShow fewer sources

  9. Delevett AF, Recalde M "Diuretic-induced renal colic." JAMA 225 (1973): 992
  10. 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
  11. 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
  12. Bennett WM, Porter GA "Efficacy and safety of metolazone in renal failure and the nephrotic syndrome." J Clin Pharmacol 13 (1973): 357-64
  13. 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
  14. Acchiardo SR, Skoutakis VA "Clinical efficacy, safety, and pharmacokinetics of indapamide in renal impairment." Am Heart J 106 (1983): 237-44
  15. Brennan L, Wu MJ, Laquer UJ "A multicenter study of indapamide in hypertensive patients with impaired renal function." Clin Ther 5 (1982): 121-8
  16. Klunk LJ, Ringel S, Neiss ES "The disposition of 14C-indapamide in man." J Clin Pharmacol 23 (1983): 377-84
  17. Newstead CG, Moore RH, Barnes AJ "Interstitial nephritis associated with indapamide." BMJ 300 (1990): 1344
  18. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  19. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):
  20. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  21. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  22. Seyffart, G "Drug Dosage in Renal Insufficiency." Dordrecht, The Netherlands: Kluwer Academic Publishers 1 (1991): 227-8
  23. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):
  24. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):
  25. Hobbs DC, Twomey TM "Kinetics of polythiazide." Clin Pharmacol Ther 23 (1978): 241-6
  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. Brors O, Jacobsen S "Distribution of elimination of hydroflumethiazide in man." Eur J Clin Pharmacol 16 (1979): 125-31
  28. Brors O, Haffner JF, Jacobsen S "Excretion of hydroflumethiazide in bile and urine of man." Eur J Clin Pharmacol 15 (1979): 287-9
  29. Yakatan GJ, Smith RB, Frome EL, Doluisio JT "Pharmacokinetics of orally administered hydroflumethiazide in man." J Clin Pharmacol 17 (1977): 37-47
  30. el-Meheiry MM, Nabih AE, Soliman MD "A clinical study of a new diuretic, Trichlormethiazide." J Trop Med Hyg 69 (1966): 209-14
  31. 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
  32. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  33. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):
  34. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):
  35. Larsson GB, Langer L, Nassberger L "Thiazide-induced kidney damage with circulating antibodies against myeloperoxidase and cardiolipin." J Intern Med 233 (1993): 493-4
  36. Beermann B, Groschinsky-Grind M, Lindstrom B "Pharmacokinetics of bendroflumethiazide." Clin Pharmacol Ther 22 (1977): 385-8
  37. Beermann B, Groschinsky-Grind M, Lindstrom B, Wikland B "Pharmacokinetics of bendroflumenthiazide in hypertensive patients." Eur J Clin Pharmacol 13 (1978): 119-24
  38. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  39. Read SJ, Trenerry HM, Whiting GF "Hyponatraemia and raised creatine kinase level associated with indapamide." Med J Aust 161 (1994): 607-8
  40. 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
  41. Brater DC "Drug therapy: Diuretic therapy." N Engl J Med 339 (1998): 387-95

• Liver Diseases

  Major

  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).

  12 sources

  1. Aneckstein AG, Weingold AB "Chlorothiazide-induced hepatic coma in pregnancy." Am J Obstet Gynecol 95 (1966): 136-7
  2. Sherlock S, Senewiratne B, Scott A, Walker JG "Complications of diuretic therapy in hepatic cirrhosis." Lancet 1 (1966): 1049-52
  3. 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
  4. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  5. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):
  6. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  7. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):
  8. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):

  Show all 12 sourcesShow fewer sources

  9. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  10. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):
  11. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):
  12. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.

• Lupus Erythematosus, Systemic

  Major

  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.

  14 sources

  1. 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
  2. Parodi A, Romagnoli M, Rebora A "Subacute cutaneous lupus erythematosus-like eruption caused by hydrochlorothiazide." Photodermatol 6 (1989): 100-2
  3. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  4. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):
  5. Goodrich AL, Kohn SR "Hydrochlorothiazide-induced lupus erythematosus: a new variant?" J Am Acad Dermatol 28 (1993): 1001-2
  6. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  7. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):
  8. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):

  Show all 14 sourcesShow fewer sources

  9. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  10. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):
  11. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):
  12. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  13. Rich MW, Eckman JM "Can hydrochlorothiazide cause lupus?" J Rheumatol 22 (1995): 1001
  14. Brown CW, Deng JS "Thiazide diuretics induce cutaneous lupus-like adverse reaction." J Toxicol Clin Toxicol 33 (1995): 729-33

• Water-Electrolyte Imbalance

  Major

  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.

  78 sources

  1. Lindy S, Tarssanen L "Serum calcium and phosphorus in patients treated with thiazides and furosemide." Acta Med Scand 194 (1973): 319-22
  2. Leigh H "Letter: Factitious hypokalemia." Ann Intern Med 80 (1974): 111-2
  3. Moore TD, Bechtel TP "Hyponatremia secondary to tolbutamide and chlorothiazide." Am J Hosp Pharm 36 (1979): 1107-10
  4. 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
  5. 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
  6. 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
  7. 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
  8. Katz FH, Eckert RC, Gebott MD "Hypokalemia caused by surreptitious self-administration of diuretics." Ann Intern Med 76 (1972): 85-90

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  9. Fichman MP, Vorherr H, Kleeman CR, Telfer N "Diuretic-induced hyponatremia." Ann Intern Med 75 (1971): 853-63
  10. 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
  11. 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
  12. 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
  13. Navarro RP, O'Brien DK, Nuffort P, Spencer DL "Diuretic induced hypokalemia in the elderly." J Fam Pract 14 (1982): 685-9
  14. Oh SJ, Douglas JE, Brown RA "Hypokalemic vacuolar myopathy associated with chlorthalidone treatment." JAMA 216 (1971): 1858-9
  15. 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
  16. Jensen OB, Mosdal C, Reske-Nielsen E "Hypokalemic myopathy during treatment with diuretics." Acta Neurol Scand 55 (1977): 465-82
  17. Cembrowski GS, Huntington RW, 3d "Probable fatal cardiac dysrhythmia secondary to diuretic-induced hypokalemia." Am J Forensic Med Pathol 2 (1981): 243-8
  18. Sumiye L, Vivian AS, Frisof KB, Podany EC "Potassium loss associated with hydrochlorothiazide versus chlorthalidone." Clin Ther 4 (1981): 308-20
  19. 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
  20. Chowdhury FR, Bleicher SJ "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res 2 (1970): 13-6
  21. Carney SL, Morgan TO "Diuretic-induced hypokalemia and altered renal function." Int J Clin Pharmacol Ther Toxicol 24 (1986): 665-7
  22. 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
  23. Hollifield JW, Slaton PE "Thiazide diuretics, hypokalemia and cardiac arrhythmias." Acta Med Scand Suppl 647 (1981): 67-73
  24. 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
  25. 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
  26. Krishna GG, Narins RG "Hemodynamic consequences of diuretic-induced hypokalemia." Am J Kidney Dis 12 (1988): 329-31
  27. Polanska AI, Baron DN "Hyponatraemia associated with hydrochlorothiazide treatment ." Br Med J 1 (1978): 175-6
  28. Pinnock CA "Hyponatraemia associated with hydrochlorothiazide treatment ." Br Med J 1 (1978): 48
  29. Itescu S, Haskell LP, Tannenberg AM "Thiazide-induced clinically significant hypophosphatemia ." Clin Nephrol 27 (1987): 161-2
  30. Byatt CM, Millard PH, Levin GE "Diuretics and electrolyte disturbances in 1000 consecutive geriatric admissions." J R Soc Med 83 (1990): 704-8
  31. Bain PG, Egner W, Walker PR "Thiazide-induced dilutional hyponatraemia masquerading as subarachnoid haemorrhage ." Lancet 2 (1986): 634
  32. 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
  33. Gould L, Reddy CV, Zen B, Singh BK "Life-threatening reaction to thiazides." N Y State J Med 80 (1980): 1975-6
  34. Seelig CB "Magnesium deficiency in two hypertensive patient groups." South Med J 83 (1990): 739-42
  35. 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,
  36. Kone B, Gimenez L, Watson AJ "Thiazide-induced hyponatremia." South Med J 79 (1986): 1456-7
  37. 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
  38. Mouallem M, Friedman E, Shemesh Y, Mayan H, Pauzner R, Farfel Z "Cardiac conduction defects associated with hyponatremia." Clin Cardiol 14 (1991): 165-8
  39. Kaur J, Wahi PL "Polythiazide as a diuretic. A clinical trial." J Indian Med Assoc 48 (1967): 13-7
  40. Mroczek WJ "Indapamide: clinical pharmacology, therapeutic efficacy in hypertension, and adverse effects." Pharmacotherapy 3 (1983): 61-7
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  44. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):
  45. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  46. Stern A "Metolazone, a diuretic agent." Am Heart J 91 (1976): 262-3
  47. Black W, Shiner P, Roman J "Severe electrolyte disturbances associated with metolazone and furosemide." South Med J 71 (1978): 381
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  49. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):
  50. Ghose RR "Letter: Hyponatraemia and diuretics." Lancet 1 (1975): 578-9
  51. 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
  52. 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
  53. el-Meheiry MM, Nabih AE, Soliman MD "A clinical study of a new diuretic, Trichlormethiazide." J Trop Med Hyg 69 (1966): 209-14
  54. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  55. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):
  56. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):
  57. Husby S, Marthedal NJ "Hyponatraemia due to a thiazide diuretic. A case report." Acta Med Scand 210 (1981): 523-4
  58. Berglund G, Andersson O, Larsson O, Wilhelmsen L "Antihypertensive effect and side-effects of bendroflumethiazide and propranolol." Acta Med Scand 199 (1976): 499-506
  59. 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
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  61. Condon JR, Nassim R "Hypophosphataemia and hypokalaemia." Br Med J 1 (1970): 110
  62. 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
  63. Lee MR, Morgan DB "Familial hyperkalaemia responsive to benzothiadiazine diuretic." Lancet 1 (1980): 879
  64. Hesp R, Wilkinson PR "Potassium supplementation of thiazide therapy." Lancet 2 (1976): 1144
  65. Struthers AD, Whitesmith R, Reid JL "Prior thiazide diuretic treatment increases adrenaline-induced hypokalaemia." Lancet 1 (1983): 1358-61
  66. 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
  67. Starr JM, Whalley LJ "Hypertensive Old People in Edinburgh (HOPE) Study: electrocardiographic changes after captopril or bendrofluazide treatment." Age Ageing 22 (1993): 343-8
  68. Toner JM, Ramsay LE "Thiazide-induced hypokalaemia; prevalence higher in women." Br J Clin Pharmacol 18 (1984): 449-52
  69. 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
  70. 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
  71. 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
  72. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  73. Freis ED "The efficacy and safety of diuretics in treating hypertension." Ann Intern Med 122 (1995): 223-6
  74. Read SJ, Trenerry HM, Whiting GF "Hyponatraemia and raised creatine kinase level associated with indapamide." Med J Aust 161 (1994): 607-8
  75. Chan TY "Indapamide-induced severe hyponatremia and hypokalemia." Ann Pharmacother 29 (1995): 1124-8
  76. 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
  77. Brater DC "Drug therapy: Diuretic therapy." N Engl J Med 339 (1998): 387-95
  78. Palmer BF, Gates JR, Lader M "Causes and management of hyponatremia." Ann Pharmacother 37 (2003): 1694-702

• Asthma

  Moderate

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

  9 sources

  1. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  2. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):
  3. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  4. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):
  5. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):
  6. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  7. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):
  8. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):

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  9. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.

• Diabetes Mellitus

  Moderate

  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.

  36 sources

  1. 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
  2. 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
  3. Miller NR, Moses H "Transient oculomotor nerve palsy. Association with thiazide-induced glucose intolerance." JAMA 240 (1978): 1887-8
  4. Kansal PC, Buse J, Buse MG "Thiazide diuretics and control of diabetes mellitus." South Med J 62 (1969): 1372-9
  5. Andersen OO, Persson I "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J 2 (1968): 798-801
  6. Curtis J, Horrigan F, Ahearn D, Varney R, Sandler SG "Chlorthalidone-induced hyperosmolar hyperglycemic nonketotic coma." JAMA 220 (1972): 1592-3
  7. Chowdhury FR, Bleicher SJ "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res 2 (1970): 13-6
  8. Diamond MT "Hyperglycemic hyperosmolar coma associated with hydrochlorothiazide and pancreatitis." N Y State J Med 72 (1972): 1741-2

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  9. Jones IG, Pickens PT "Diabetes mellitus following oral diuretics." Practitioner 199 (1967): 209-10
  10. Beling S, Vukovich RA, Neiss ES, Zisblatt M, Webb E, Losi M "Long-term experience with indapamide." Am Heart J 106 (1983): 258-62
  11. Slotkoff L "Clinical efficacy and safety of indapamide in the treatment of edema." Am Heart J 106 (1983): 233-7
  12. 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
  13. Seltzer HS, Allen EW "Hyperglycemia and inhibition of insulin secretion during administration of diazoxide and trichlormethiazide in man." Diabetes 18 (1969): 19-28
  14. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  15. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):
  16. Bell DS "Insulin resistance. An often unrecognized problem accompanying chronic medical disorders." Postgrad Med 93 (1993): 99-103,
  17. Berlin I "Prazosin, diuretics, and glucose intolerance." Ann Intern Med 119 (1993): 860
  18. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  19. Rowe P, Mather H "Hyperosmolar non-ketotic diabetes mellitus associated with metolazone." Br Med J 291 (1985): 25-6
  20. Domenet JG "Diabetogenic effect of oral diuretics." Br Med J 3 (1968): 188
  21. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):
  22. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):
  23. 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
  24. 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
  25. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  26. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):
  27. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):
  28. 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
  29. 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
  30. 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
  31. 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
  32. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  33. Freis ED "The efficacy and safety of diuretics in treating hypertension." Ann Intern Med 122 (1995): 223-6
  34. 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
  35. 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
  36. 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

• Heart Failure

  Moderate

  Angiotensin II receptor (AR) antagonists can cause renal impairment in patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system. In addition, symptomatic hypotension can occur in susceptible individuals, which may compromise renal and myocardial perfusion. In patients with severe congestive heart failure (CHF), treatment with AR antagonists has been associated with oliguria and/or progressive azotemia and, rarely, renal failure, myocardial ischemia, and death. Therapy with AR antagonists should be initiated cautiously in patients with severe CHF, especially when accompanied by volume and/or sodium depletion. In patients who experience a decline in renal function, discontinuation of AR antagonist therapy is usually not required provided there is symptomatic improvement of the heart failure and renal deterioration is well-tolerated. Transient hypotension is also not a contraindication to further treatment with AR antagonists, since therapy can usually be reinstated without difficulty after blood pressure stabilizes.

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  1. Weber MA, Byyny RL, Pratt JH, Faison EP, Snavely DB, Goldberg AI, Nelson EB "Blood pressure effects of the angiotensin II receptor blocker, losartan." Arch Intern Med 155 (1995): 405-11
  2. Crozier I, Ikram H, Awan N, Cleland J, Stephen N, Dickstein K, Frey M, Young J, Klinger G, Makris L, et al. "Losartan in heart failure. Hemodynamic effects and tolerability. Losartan Hemodynamic Study Group." Circulation 91 (1995): 691-7
  3. Gottlieb SS, Dickstein K, Fleck E, Kostis J, Levine TB, LeJemtel T, DeKock M "Hemodynamic and neurohormonal effects of the angiotensin II antagonist losartan in patients with congestive heart failure." Circulation 88 (1993): 1602-9
  4. Goldberg MR, Bradstreet TE, McWilliams EJ, Tanaka WK, Lipert S, Bjornsson TD, Waldman SA, Osborne B, Pivadori L, Lewis G, et al. "Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients." Hypertension 25 (1995): 37-46
  5. Goldberg MR, Tanaka W, Barchowsky A, Bradstreet TE, McCrea J, Lo MW, McWilliams EJ Jr, Bjornsson TD "Effects of losartan on blood pressure, plasma renin activity, and angiotensin II in volunteers." Hypertension 21 (1993): 704-13
  6. Doig JK, MacFadyen RJ, Sweet CS, Lees KR, Reid JL "Dose-ranging study of the angiotensin type I receptor antagonist losartan (DuP753/MK954), in salt-deplete normal man." J Cardiovasc Pharmacol 21 (1993): 732-8
  7. Dickstein K, Gottlieb S, Fleck E, Kostis J, Levine B, DeKock M, LeJemtel T "Hemodynamic and neurohumoral effects of the angiotensin II antagonist losartan in patients with heart failure." J Hypertens Suppl 12 (1994): s31-5
  8. Abdelrahman AM, Burrell LM, Johnston CI "Blockade of the renin-angiotensin system at different sites: effect on renin, angiotensin and aldosterone." J Hypertens 11 Suppl 3 (1993): s23-6

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  9. Rush JE, Rajfer SI "Theoretical basis for the use of angiotensin II antagonists in the treatment of heart failure." J Hypertens 11 Suppl 3 (1993): s69-71
  10. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  11. Crozier I, Ikram H "The acute and chronic effects of losartan in heart failure." J Hypertens 13 Suppl (1995): s59-61
  12. Saine DR, Ahrens ER "Renal impairment associated with losartan." Ann Intern Med 124 (1996): 775
  13. Schaefer KL, Porter JA "Angiotensin II receptor antagonists: the prototype losartan." Ann Pharmacother 30 (1996): 625-36
  14. Waeber B, Brunner HR "Angiotensin II antagonists: a new class of antihypertensive agent." Br J Clin Pract 50 (1996): 265-8
  15. Gibbs CR, Ferner RE, Beevers DG "Angiotensin receptor antagonists - a new class of antihypertensive drug." J Clin Pharm Ther 21 (1996): 127-30
  16. Ellis ML, Patterson H "A new class of antihypertensive therapy: angiotensin II receptor antagonists." Pharmacotherapy 16 (1996): 849-60
  17. Holwerda NJ, Fogari R, Angeli P, et al. "Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril." J Hypertens 14 (1996): 1147-115
  18. Waeber B, Burnier M, Nussberger J, Brunner HR "Experience with angiotensin II antagonists in hypertensive patients." Clin Exp Pharmacol Physiol 23 ( Suppl (1996): s142-6
  19. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  20. Pitt B, Segal R, Martinez FA, et al. "Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE)." Lancet 349 (1997): 747-52
  21. van den Meiracker AH, Admiraal PJ, Janssen JA, Kroodsma JM, de Ronde WA, Boomsma F, Sissmann J, Blankestijn PJ, Mulder PG, Man In 't Veld AJ "Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension." Hypertension 25 (1995): 22-9
  22. McIntyre M, MacFadyen RJ, Meredith PA, Brouard R, Reid JL "Dose-ranging study of the angiotensin II receptor antagonist irbesartan (SR 47436/BMS-186295) on blood pressure and neurohormona effects in salt-deplete men." J Cardiovasc Pharmacol 28 (1996): 101-6
  23. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  24. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  25. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  26. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  27. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  28. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Hyperkalemia

  Moderate

  Drugs that inhibit the renin-angiotensin, such as angiotensin II receptor antagonist system can cause hyperkalemia. Concomitant use of these agents with drugs that increase potassium levels may increase the risk of hyperkalemia. Use caution when using these agents together and monitor serum potassium periodically.

  8 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  4. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  5. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  6. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  7. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  8. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Hyperlipidemias

  Moderate

  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

  23 sources

  1. 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
  2. Ames RP, Hill P "Increase in serum-lipids during treatment of hypertension with chlorthalidone." Lancet 1 (1976): 721-3
  3. 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
  4. 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
  5. Beling S, Vukovich RA, Neiss ES, Zisblatt M, Webb E, Losi M "Long-term experience with indapamide." Am Heart J 106 (1983): 258-62
  6. Slotkoff L "Clinical efficacy and safety of indapamide in the treatment of edema." Am Heart J 106 (1983): 233-7
  7. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  8. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):

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  9. 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
  10. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  11. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):
  12. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):
  13. Smith WM "Diuretics and cholesterol elevation." JAMA 242 (1979): 1612
  14. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  15. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):
  16. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):
  17. 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
  18. 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
  19. 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
  20. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  21. Kasiske BL, Ma JZ, Kalil RS, Louis TA "Effects of antihypertensive therapy on serum lipids." Ann Intern Med 122 (1995): 133-41
  22. Freis ED "The efficacy and safety of diuretics in treating hypertension." Ann Intern Med 122 (1995): 223-6
  23. 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

• Hyperparathyroidism

  Moderate

  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.

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  1. Anderson PE, Ellis GG, Austin SM "Case report: metolazone-associated hypercalcemia and acute pancreatitis." Am J Med Sci 302 (1991): 235-7
  2. Lindy S, Tarssanen L "Serum calcium and phosphorus in patients treated with thiazides and furosemide." Acta Med Scand 194 (1973): 319-22
  3. Gammon GD, Docherty JP "Thiazide-induced hypercalcemia in a manic-depressive patient." Am J Psychiatry 137 (1980): 1453-5
  4. Parfitt AM "Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism." Ann Intern Med 77 (1972): 557-63
  5. 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
  6. Paloyan E, Farland M, Pickleman JR "Hyperparathyroidism coexisting with hypertension and prolonged thiazide administration." JAMA 210 (1969): 1243-5
  7. Parfitt AM "Chlorothiazide-induced hypercalcemia in juvenile osteoporosis and hyperparathyroidism." N Engl J Med 281 (1969): 55-9
  8. Palmer FJ "Letter: Chlorthalidone-induced hypercalcemia." JAMA 229 (1974): 267

  Show all 27 sourcesShow fewer sources

  9. 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
  10. Itescu S, Haskell LP, Tannenberg AM "Thiazide-induced clinically significant hypophosphatemia ." Clin Nephrol 27 (1987): 161-2
  11. Byatt CM, Millard PH, Levin GE "Diuretics and electrolyte disturbances in 1000 consecutive geriatric admissions." J R Soc Med 83 (1990): 704-8
  12. Balizet L "Recurrent parathyroid adenoma. Association with prolonged thiazide administration." JAMA 225 (1973): 1238-9
  13. Paloyan E, Farland M, Pickleman JR "Hyperparathyroidism coexisting with hypertension and prolonged thiazide administration." JAMA 210 (1969): 1243-5
  14. Duarte CG, Winnacker JL, Becker KL, Pace A "Thiazide-induced hypercalcemia." N Engl J Med 284 (1971): 828-30
  15. Klimiuk PS, Davies M, Adams PH "Primary hyperparathyroidism and thiazide diuretics." Postgrad Med J 57 (1981): 80-3
  16. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  17. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):
  18. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  19. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):
  20. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):
  21. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  22. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):
  23. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):
  24. Hilker RR "Reversible hypercalcemia associated with prolonged thiazide administration to control hypertension." J Occup Med 12 (1970): 444-5
  25. 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
  26. 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
  27. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.

• Hyperuricemia

  Moderate

  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.

  20 sources

  1. Lapidus PW, Guidotti FP "Gout in orthopaedic practice: review of 232 cases." Clin Orthop 28 (1963): 97-110
  2. 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
  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. Slotkoff L "Clinical efficacy and safety of indapamide in the treatment of edema." Am Heart J 106 (1983): 233-7
  5. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  6. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):
  7. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  8. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):

  Show all 20 sourcesShow fewer sources

  9. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):
  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. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  12. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):
  13. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.
  20. Freis ED "The efficacy and safety of diuretics in treating hypertension." Ann Intern Med 122 (1995): 223-6

• Kidney Diseases

  Moderate

  Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure with these agents. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function with these agents.

  8 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  4. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  5. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  6. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  7. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  8. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Liver Diseases

  Moderate

  Candesartan is eliminated by the kidney as well as by biliary excretion. Dosage adjustments are not necessary in patients with mild renal impairment unless they are also volume-depleted, in which case therapy should be initiated under medical supervision. Likewise, patients with mild hepatic impairment or biliary obstruction generally do not require a dosage adjustment. However, reduced dosages may be appropriate in patients with severe renal, liver, and/or biliary disease.

  2 sources

  1. Meineke I, Feltkamp H, Hogemann A, Gundert-Remy U "Pharmacokinetics and pharmacodynamics of candesartan after administration of its pro-drug candesartan cilexetil in patients wit mild to moderate essential hypertension--a population analysis." Eur J Clin Pharmacol 53 (1997): 221-8
  2. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):

• Renal Artery Obstruction

  Moderate

  In patients with bilateral renal artery stenosis or renal artery stenosis in a solitary kidney, angiotensin II receptor (AR) antagonists may reduce renal perfusion to a critically low level. Increases in serum creatinine or blood urea nitrogen have been reported with ACE inhibitors, a class of drugs that also block the renin-angiotensin-aldosterone system. Although there are no long-term data on the use of AR antagonists in patients with renal artery stenosis, a similar effect should be anticipated. Renal function should be monitored closely for the first few weeks of therapy.

  8 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  4. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  5. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  6. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  7. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  8. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Thyroid Diseases

  Moderate

  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.

  10 sources

  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. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  3. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer (2002):
  4. "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer (2001):
  5. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):
  6. "Product Information. Diuril (chlorothiazide)." Merck & Co., Inc (2001):
  7. "Product Information. Enduron (methyclothiazide)." Abbott Pharmaceutical (2001):
  8. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion Roussel (2001):

  Show all 10 sourcesShow fewer sources

  9. "Product Information. Diucardin (hydroflumethiazide)." Wyeth-Ayerst Laboratories (2001):
  10. "Product Information. Renese-R (reserpine-polythiazide)." Pfizer US Pharmaceuticals, New York, NY.

Therapeutic duplication

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

• angiotensin ii inhibitors

  The recommended maximum number of medicines in the 'angiotensin II inhibitors' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'angiotensin II inhibitors' category.

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

• thiazide and thiazide-like diure

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

  Example product in the source data (US market): Tenoretic 50

• thiazide and thiazide-like diure

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

  Example product in the source data (US market): Bendroflumethiazide/nadolol