Perindopril + Indapamide 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 can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

  What to do: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes.

  3 sources

  1. "Product Information. Vasotec (enalapril)." Merck & Co., Inc (2002):
  2. Good CB, McDermott L "Diet and serum potassium in patients on ACE inhibitors." JAMA 274 (1995): 538
  3. Ray K, Dorman S, Watson R "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens 13 (1999): 717-20

Conditions

Conditions in which Perindopril + Indapamide needs care, as documented in this source.

• Angioedema

  Major

  The use of these agents is contraindicated in patients with hereditary angioedema or a history of idiopathic angioedema. Patients with a history of angioedema unrelated to ACE inhibitors may be at increased risk of angioedema while receiving an ACE inhibitor. 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 ACE inhibitors should be discontinued permanently if angioedema develops in association with therapy.

  34 sources

  1. Suarez M, Ho PW, Johnson ES, Perez G "Angioneurotic edema, agranulocytosis, and fatal septicemia following captopril therapy." Am J Med 81 (1986): 336-8
  2. Roberts JR, Wuerz RC "Clinical characteristics of angiotensin-converting enzyme inhibitor-induced angioedema." Ann Emerg Med 20 (1991): 555-8
  3. Jett GK "Captopril-induced angioedema ." Ann Emerg Med 13 (1984): 489-90
  4. McElligott S, Perlroth M, Raish L "Angioedema after substituting lisinopril for captopril ." Ann Intern Med 116 (1992): 426-7
  5. Hedner T, Samuelsson O, Lunde H, et al. "Angio-oedema in relation to treatment with angiotensin converting enzyme inhibitors." Br Med J 304 (1992): 941-6
  6. Wood SM, Mann RD, Rawlins MD "Angio-oedema and urticaria associated with angiotensin converting enzyme inhibitors." Br Med J 294 (1987): 91-2
  7. Seidman MD, Lewandowski CA, Sarpa JR, et al. "Angioedema related to angiotensin-converting enzyme inhibitors." Otolaryngol Head Neck Surg 102 (1990): 727-31
  8. Werber JL, Pincus RL "Oropharyngeal angioedema associated with the use of angiotensin-converting enzyme inhibitors." Otolaryngol Head Neck Surg 101 (1989): 96-8

  Show all 34 sourcesShow fewer sources

  9. Jason DR "Fatal angioedema associated with captopril." J Forensic Sci 37 (1992): 1418-21
  10. Gianos ME, Klaustermeyer WB, Kurohara M, et al. "Enalapril induced angioedema." Am J Emerg Med 8 (1990): 124-6
  11. Gonnering RS, Hirsch SR "Delayed drug-induced periorbital angioedema ." Am J Ophthalmol 110 (1990): 566-8
  12. Chin HL, Buchan DA "Severe angioedema after long-term use of an angiotensin-converting enzyme inhibitor ." Ann Intern Med 112 (1990): 312-3
  13. Abidin MR, Eisele DW "Angioedema after long-term use of angiotensin-converting enzyme inhibitor ." Arch Otolaryngol Head Neck Surg 117 (1991): 1059
  14. Orfan N, Patterson R, Dykewicz MS "Severe angioedema related to ACE inhibitors in patients with a history of idiopathic angioedema." JAMA 264 (1990): 1287-9
  15. Gannon TH, Eby TL "Angioedema from angiotensin converting enzyme inhibitors: a cause of upper airway obstruction." Laryngoscope 100 (1990): 1156-60
  16. "Product Information. Lotensin (benazepril)." Ciba-Geigy Pharmaceuticals (2002):
  17. "Product Information. Capoten (captopril)." Bristol-Myers Squibb (2002):
  18. "Product Information. Vasotec (enalapril)." Merck & Co., Inc (2002):
  19. "Product Information. Prinivil (lisinopril)." Merck & Co., Inc (2002):
  20. Soo Hoo GW, Dao HT, Klaustermeyer WB "Severe angioedema and respiratory distress associated with lisinopril use." West J Med 158 (1993): 412-7
  21. "Product Information. Accupril (quinapril)." Parke-Davis (2001):
  22. "Product Information. Monopril (fosinopril)." Bristol-Myers Squibb (2001):
  23. "Product Information. Altace (ramipril)." Hoechst Marion Roussel (2001):
  24. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc (2001):
  25. Frontera Y, Piecuch JF "Multiple episodes of angioedema associated with lisinopril, an ACE inhibitor." J Am Dent Assoc 126 (1995): 217-20
  26. Gimenez JC "Angioneurotic edema produced by enalapril." Ann Pharmacother 29 (1995): 317
  27. Gonzalo FE, Montagut LB, Vecina ST "Angioedema caused by ramipril." Ann Pharmacother 29 (1995): 431-2
  28. "Product Information. Univasc (moexipril)." Schwarz Pharma (2001):
  29. Forslund T, Tohmo H, Weckstrom G, Stenborg M, Jarvinen S "Angio-oedema induced by enalapril." J Intern Med 238 (1995): 179-81
  30. Alderman CP "Adverse effects of the angiotensin-converting enzyme inhibitors." Ann Pharmacother 30 (1996): 55-61
  31. "Product Information. Mavik (trandolapril)." Knoll Pharmaceutical Company (2001):
  32. Gunkel AR, Thurner KH, Kanonier G, Sprinzl GM, Thumfart WF "Angioneurotic edema as a reaction to angiotensin-converting enzyme inhibitors." Am J Otolaryngol 17 (1996): 87-91
  33. O'Mara NB, O'Mara EM Jr "Delayed onset of andioedema with angiotensin-converting enzyme inhibitors: case report and review of the literature." Pharmacotherapy 16 (1996): 675-9
  34. Kaplan NM "The CARE study: a postmarketing evaluation of ramipril in 11,100 patients." Clin Ther 18 (1996): 658-70

• 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.

• Bone Marrow Failure Disorders

  Major

  ACE inhibitors may cause bone marrow suppression, rarely in uncomplicated individuals but more frequently in patients with renal impairment, especially if they also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma. Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, eosinophilia and thrombocytopenia have been reported, mostly with captopril. Therapy with ACE inhibitors should be administered cautiously in patients with preexisting blood dyscrasias or complications that may increase the risk of bone marrow depression during ACE inhibitor therapy. Monitoring of blood counts, particularly white blood cells, should be considered.

  38 sources

  1. Elijovisch F, Krakoff LR "Captopril associated granulocytopenia in hypertension after renal transplantation." Lancet 1 (1980): 927-8
  2. Vidt DG, Bravo EL, Fouad FM "Captopril." N Engl J Med 306 (1982): 214-9
  3. Kim CR, Maley MB, Mohler ER "Captopril and aplastic anemia." Ann Intern Med 111 (1989): 187-8
  4. Davies RO, Irvin JD, Kramsch PK, Walker JF, Moncloa F "Enalapril worldwide experience." Am J Med 77 (1984): 23-35
  5. Chalmers D, Whitehead A, Lawson DH "Postmarketing surveillance of captopril for hypertension." Br J Clin Pharmacol 34 (1992): 215-23
  6. Suarez M, Ho PW, Johnson ES, Perez G "Angioneurotic edema, agranulocytosis, and fatal septicemia following captopril therapy." Am J Med 81 (1986): 336-8
  7. Gavras I, Graff LG, Rose BD, et al. "Fatal pancytopenia associated with the use of captopril." Ann Intern Med 94 (1981): 58-9
  8. Grosbois B, Milton D, Beneton C, Jacomy D "Thrombocytopenia induced by angiotensin converting enzyme inhibitors." Br Med J 298 (1989): 189-90

  Show all 38 sourcesShow fewer sources

  9. el-Makri A, Larabi MS, Kechrid C, et al. "Fatal bone-marrow suppression associated with captopril." Br Med J 283 (1981): 277-8
  10. Strair RK, Mitch WE, Faller DV, Skorecki KL "Reversible captopril-associated bone marrow aplasia ." Can Med Assoc J 132 (1985): 320-2
  11. Shindo K, Matsuya F, Ura T, et al. "Captopril-associated granulocytopenia in hypertension after renal transplantation." Clin Nephrol 22 (1984): 314-6
  12. Forslund T, Borgmastars H, Fyrquist F "Captopril-associated leucopenia confirmed by rechallenge in patient with renal failure ." Lancet 1 (1981): 166
  13. Elijovisch F, Krakoff LR "Captopril associated granulocytopenia in hypertension after renal transplantation ." Lancet 1 (1980): 927-8
  14. Pillans PI, Koopowitz A "Captopril-associated agranulocytosis: a report of 3 cases." S Afr Med J 79 (1991): 399-400
  15. Israeli A, Or R, Leitersdorf E "Captopril-associated transient aplastic anemia." Acta Haematol 73 (1985): 106-7
  16. Hirakata H, Onoyama K, Iseki K, et al. "Worsening of anemia induced by long-term use of captopril in hemodialysis patients." Am J Nephrol 4 (1984): 355-60
  17. Edwards IR, Coulter DM, Beasley DM, MacIntosh D "Captopril: 4 years of post marketing surveillance of all patients in New Zealand." Br J Clin Pharmacol 23 (1987): 529-36
  18. Torello J, Duran JA, Abadin JA "Captopril-associated aplastic anemia ." Drug Intell Clin Pharm 24 (1990): 543-4
  19. Onoyama K, Sanai T, Motomura K, Fujishima M "Worsening of anemia by angiotensin converting enzyme inhibitors and its prevention by antiestrogenic steroid in chronic hemodialysis patients." J Cardiovasc Pharmacol 13 (1989): s27-30
  20. Waeber B, Gavras I, Brunner HR, Gavras H "Safety and efficacy of chronic therapy with captopril in hypertensive patients: an update." J Clin Pharmacol 21 (1981): 508-16
  21. Beroniade V "Severe side-effects of captopril in advanced chronic kidney insufficiency." Proc Eur Dial Transplant Assoc 20 (1983): 530-7
  22. Vlahakos DV, Canzanello VJ, Madaio MP, Madias NE "Enalapril-associated anemia in renal transplant recipients treated for hypertension." Am J Kidney Dis 17 (1991): 199-205
  23. Loftus WK, Ierino F, Mathew TH "Enalapril and anaemia ." Med J Aust 148 (1988): 209-10
  24. Elis A, Lishner M, Lang R, Ravid M "Agranulocytosis associated with enalapril." Drug Intell Clin Pharm 25 (1991): 461-2
  25. Knapp LE, Frank GJ, McLain R, Rieger MM, Posvar E, Singer R "The safety and tolerability of quinapril." J Cardiovasc Pharmacol 15 (1990): s47-55
  26. Materson BJ "Adverse effects of angiotensin-converting enzyme inhibitors in antihypertensive therapy with focus on quinapril." Am J Cardiol 69 (1992): c46-53
  27. "Product Information. Lotensin (benazepril)." Ciba-Geigy Pharmaceuticals (2002):
  28. "Product Information. Capoten (captopril)." Bristol-Myers Squibb (2002):
  29. "Product Information. Vasotec (enalapril)." Merck & Co., Inc (2002):
  30. "Product Information. Prinivil (lisinopril)." Merck & Co., Inc (2002):
  31. "Product Information. Accupril (quinapril)." Parke-Davis (2001):
  32. "Product Information. Monopril (fosinopril)." Bristol-Myers Squibb (2001):
  33. "Product Information. Altace (ramipril)." Hoechst Marion Roussel (2001):
  34. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc (2001):
  35. "Product Information. Univasc (moexipril)." Schwarz Pharma (2001):
  36. Harrison BD, Laidlaw ST, Reilly JT "Fatal aplastic anaemia associated with lisinopril." Lancet 346 (1995): 247-8
  37. Alderman CP "Adverse effects of the angiotensin-converting enzyme inhibitors." Ann Pharmacother 30 (1996): 55-61
  38. "Product Information. Mavik (trandolapril)." Knoll Pharmaceutical Company (2001):

• Diseases requiring hemodialysis

  Major

  Anaphylactoid reactions have been reported in patients undergoing hemodialysis with high-flux polyacrylonitrile membranes and treated concomitantly with an ACE inhibitor. The frequency and mechanism of this interaction have not been established, and it is not known whether the interaction occurs with other membrane types. Therapy with ACE inhibitors should be administered cautiously in patients requiring hemodialysis.

  10 sources

  1. "Product Information. Lotensin (benazepril)." Ciba-Geigy Pharmaceuticals (2002):
  2. "Product Information. Capoten (captopril)." Bristol-Myers Squibb (2002):
  3. "Product Information. Vasotec (enalapril)." Merck & Co., Inc (2002):
  4. "Product Information. Prinivil (lisinopril)." Merck & Co., Inc (2002):
  5. "Product Information. Accupril (quinapril)." Parke-Davis (2001):
  6. "Product Information. Monopril (fosinopril)." Bristol-Myers Squibb (2001):
  7. "Product Information. Altace (ramipril)." Hoechst Marion Roussel (2001):
  8. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc (2001):

  Show all 10 sourcesShow fewer sources

  9. "Product Information. Univasc (moexipril)." Schwarz Pharma (2001):
  10. "Product Information. Mavik (trandolapril)." Knoll Pharmaceutical Company (2001):

• Heart Failure

  Major

  ACE inhibitors can cause marked renal impairment in patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system. In addition, symptomatic and sometimes excessive hypotension can occur in susceptible individuals, particularly during the initiation of treatment, which may compromise renal and myocardial perfusion. In patients with severe congestive heart failure (CHF), treatment with ACE inhibitors may be associated with oliguria and/or progressive azotemia and, rarely, renal failure, myocardial ischemia and death. Therapy with ACE inhibitors should be initiated under very close medical supervision in patients with severe CHF, especially when accompanied by volume and/or sodium depletion. Patients should be monitored closely for several hours after an initial dose until blood pressure has stabilized, and followed closely for the first 2 weeks of treatment and whenever the dosage of ACE inhibitor or diuretic is increased. If feasible, the risk of severe hypotension may be minimized by reducing or temporarily withholding the dosing of diuretics and/or liberalizing dietary sodium intake for 2 to 3 days prior to starting ACE inhibitor therapy. In patients who experience a worsening of renal function, discontinuation of ACE inhibitor 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 ACE inhibitors. After blood pressure stabilizes, therapy can usually be reinstated with caution, although a lower dosage of the ACE inhibitor and/or dosage reduction or discontinuation of concomitantly administered diuretics may be necessary.

  21 sources

  1. Schwartz D, Averbuch M, Pines A, et al. "Renal toxicity of enalapril in very elderly patients with progressive, severe congestive heart failure." Chest 100 (1991): 1558-61
  2. Ljungman S, Kjekshus J, Swedberg K "Renal function in severe congestive heart failure during treatment with enalapril." Am J Cardiol 70 (1992): 479-87
  3. Heintz B, Verho M, Brockmeier D, Kirsten R, Nelson K, Maigatter S, Lefevre G, Kierdorf H, Sieberth HG "Influence of ramipril on renal function in patients with chronic congestive heart failure." J Cardiovasc Pharmacol 18 (1991): s174-9
  4. Moyses C, Higgins TJ "Safety of long-term use of lisinopril for congestive heart failure." Am J Cardiol 70 (1992): c91-7
  5. Moyses C, Higgins TJ "Safety of long-term use of lisinopril for congestive heart failure." Am J Cardiol 70 (1992): c91-7
  6. Dietz R, Nagel F, Osterziel KJ "Angiotensin-converting enzyme inhibitors and renal function in heart failure." Am J Cardiol 70 (1992): c119-25
  7. "Product Information. Lotensin (benazepril)." Ciba-Geigy Pharmaceuticals (2002):
  8. "Product Information. Capoten (captopril)." Bristol-Myers Squibb (2002):

  Show all 21 sourcesShow fewer sources

  9. "Product Information. Vasotec (enalapril)." Merck & Co., Inc (2002):
  10. "Product Information. Prinivil (lisinopril)." Merck & Co., Inc (2002):
  11. "Product Information. Accupril (quinapril)." Parke-Davis (2001):
  12. "Product Information. Monopril (fosinopril)." Bristol-Myers Squibb (2001):
  13. "Product Information. Altace (ramipril)." Hoechst Marion Roussel (2001):
  14. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc (2001):
  15. Kostis JB, Shelton BJ, Yusuf S, Weiss MB, Capone RJ, Pepine CJ, Gosselin G, Delahaye F, Probstfield JL, Cahill L, Dutton D "Tolerability of enalapril initiation by patients with left ventricular dysfunction: results of the medication challenge phase of the studies of left ventricular dysfunction." Am Heart J 128 (1994): 358-64
  16. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  17. "Product Information. Univasc (moexipril)." Schwarz Pharma (2001):
  18. Antonios TFT, Macgregor GA "Angiotensin converting enzyme inhibitors in hypertension: potential problems." J Hypertens 13 Suppl (1995): s11-6
  19. Kostis JB, Shelton B, Gosselin G, Goulet C, Hood WB, Kohn RM, Kubo SH, Schron E, Weiss MB, Willis PW, Young JB, Probstfie "Adverse effects of enalapril in the studies of left ventricular dysfunction (SOLVD)." Am Heart J 131 (1996): 350-5
  20. Kober L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K, Videbaek J, Cole DS, Auclert L, Pauly NC, et al. "A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group." N Engl J Med 333 (1995): 1670-6
  21. "Product Information. Mavik (trandolapril)." Knoll Pharmaceutical Company (2001):

• Hyperkalemia

  Major

  In patients with hyperkalemia, especially those associated with impaired renal function or congestive heart failure, ACE inhibitors may further raise serum potassium levels. Therapy with ACE inhibitors should be administered cautiously in patients with or predisposed to hyperkalemia, and serum potassium levels should be carefully monitored. Risk factors for the development of hyperkalemia during ACE inhibitor therapy include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes.

  18 sources

  1. Kindler J, Schunkert H, Gassmann M, Lahn W, Irmisch R, Debusmann ER, Ocon-Pujadas J, Ritz E, Sieberth HG "Therapeutic efficacy and tolerance of ramipril in hypertensive patients with renal failure." J Cardiovasc Pharmacol 13 (1989): s55-8
  2. Moyses C, Higgins TJ "Safety of long-term use of lisinopril for congestive heart failure." Am J Cardiol 70 (1992): c91-7
  3. "Product Information. Lotensin (benazepril)." Ciba-Geigy Pharmaceuticals (2002):
  4. "Product Information. Capoten (captopril)." Bristol-Myers Squibb (2002):
  5. "Product Information. Vasotec (enalapril)." Merck & Co., Inc (2002):
  6. "Product Information. Prinivil (lisinopril)." Merck & Co., Inc (2002):
  7. "Product Information. Accupril (quinapril)." Parke-Davis (2001):
  8. "Product Information. Monopril (fosinopril)." Bristol-Myers Squibb (2001):

  Show all 18 sourcesShow fewer sources

  9. "Product Information. Altace (ramipril)." Hoechst Marion Roussel (2001):
  10. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc (2001):
  11. Kostis JB, Shelton BJ, Yusuf S, Weiss MB, Capone RJ, Pepine CJ, Gosselin G, Delahaye F, Probstfield JL, Cahill L, Dutton D "Tolerability of enalapril initiation by patients with left ventricular dysfunction: results of the medication challenge phase of the studies of left ventricular dysfunction." Am Heart J 128 (1994): 358-64
  12. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  13. "Product Information. Univasc (moexipril)." Schwarz Pharma (2001):
  14. Antonios TFT, Macgregor GA "Angiotensin converting enzyme inhibitors in hypertension: potential problems." J Hypertens 13 Suppl (1995): s11-6
  15. Alderman CP "Adverse effects of the angiotensin-converting enzyme inhibitors." Ann Pharmacother 30 (1996): 55-61
  16. Kostis JB, Shelton B, Gosselin G, Goulet C, Hood WB, Kohn RM, Kubo SH, Schron E, Weiss MB, Willis PW, Young JB, Probstfie "Adverse effects of enalapril in the studies of left ventricular dysfunction (SOLVD)." Am Heart J 131 (1996): 350-5
  17. "Product Information. Mavik (trandolapril)." Knoll Pharmaceutical Company (2001):
  18. Tramonti G, Donadio C, Confessore N, Bianchi C "Antihypertensive activity and renal effects of benazepril in humans." Kidney Int (suppl 5) (1996): s107-8

• Hypotension

  Major

  ACE inhibitors can cause symptomatic hypotension, most often during the initiation of therapy and in patients who are volume- and/or sodium-depleted or treated for congestive heart failure (CHF). Therapy with ACE inhibitors should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if it was recently instituted; those on dietary salt restriction; those with severe or prolonged diarrhea or vomiting; and renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with ACE inhibitors, and the patient should be hemodynamically stable. If concomitant diuretics and/or dietary sodium restriction are employed, reducing or temporarily withholding the dosing of diuretics and/or liberalizing dietary sodium intake for 2 to 3 days in advance can help minimize the risk of severe hypotension in patients who are able to tolerate such adjustments. ACE inhibitors should also be used cautiously in patients in whom excessive hypotension may have serious consequences, such as patients with coronary or cerebrovascular insufficiency. Patients at risk for excessive hypotension should initiate ACE inhibitor therapy under very close medical supervision, and followed closely for the first 2 weeks of treatment and whenever the dosage of ACE inhibitor or diuretic is increased.

  32 sources

  1. Forette B, Koen R, Vivaut E "Efficacy and safety of quinapril in the elderly hypertensive patient." Am Heart J 123 (1992): 1426-32
  2. Chalmers D, Whitehead A, Lawson DH "Postmarketing surveillance of captopril for hypertension." Br J Clin Pharmacol 34 (1992): 215-23
  3. Schnaper HW "Comparison of the efficacy and safety of quinapril vs. captopril in treatment of moderate to severe hypertension." Angiology 40 (1989): 389-95
  4. Schoenberger JA, Testa M, Ross AD, et al. "Efficacy, safety, and quality-of-life assessment of captopril antihypertensive therapy in clinical practice." Arch Intern Med 150 (1990): 301-6
  5. Edwards IR, Coulter DM, Beasley DM, MacIntosh D "Captopril: 4 years of post marketing surveillance of all patients in New Zealand." Br J Clin Pharmacol 23 (1987): 529-36
  6. Black J, Hunt TL, Godley PJ "Initiation of captopril therapy: the first-dose effect." J Clin Pharmacol 26 (1986): 539-40
  7. Russell RM, Jones RM "Postoperative hypotension associated with enalapril." Anaesthesia 44 (1989): 837-8
  8. Inman WH, Rawson NS, Wilton LV, et al. "Postmarketing surveillance of enalapril. I: results of prescription-event monitoring." Br Med J 297 (1988): 826-9

  Show all 32 sourcesShow fewer sources

  9. Cooper WD, Sheldon D, Brown D, et al. "Post-marketing surveillance of enalapril: experience in 11,710 hypertensive patients in general practice." J R Coll Gen Pract 37 (1987): 346-9
  10. Osterziel KJ, Karr M, Busch C, Dietz R "Comparison of the first-dose effect of captopril and lisinopril in heart failure." Am J Cardiol 70 (1992): c137-9
  11. MacNab M, Mallows S "Safety profile of benazepril in essential hypertension." Clin Cardiol 14 Suppl I (1991): iv33-7
  12. Balfour J, Goa K "Benazepril: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension and congestive heart failure." Drugs 42 (1991): 511-39
  13. "Product Information. Lotensin (benazepril)." Ciba-Geigy Pharmaceuticals (2002):
  14. "Product Information. Capoten (captopril)." Bristol-Myers Squibb (2002):
  15. "Product Information. Vasotec (enalapril)." Merck & Co., Inc (2002):
  16. "Product Information. Prinivil (lisinopril)." Merck & Co., Inc (2002):
  17. Young BA "ACE inhibitor first dose effect." Med J Aust 158 (1993): 577
  18. "Product Information. Accupril (quinapril)." Parke-Davis (2001):
  19. "Product Information. Monopril (fosinopril)." Bristol-Myers Squibb (2001):
  20. "Product Information. Altace (ramipril)." Hoechst Marion Roussel (2001):
  21. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc (2001):
  22. Kostis JB, Shelton BJ, Yusuf S, Weiss MB, Capone RJ, Pepine CJ, Gosselin G, Delahaye F, Probstfield JL, Cahill L, Dutton D "Tolerability of enalapril initiation by patients with left ventricular dysfunction: results of the medication challenge phase of the studies of left ventricular dysfunction." Am Heart J 128 (1994): 358-64
  23. Lang RM, Dibianco R, Broderick GT, Gottlieb SS, Kostis J, Lyle PA, Makris L, Rajfer SI, Rucinska EJ "First-dose effects of enalapril 2.5 mg and captopril 6.25 mg in patients with heart failure: a double-blind, randomized, multicenter study." Am Heart J 128 (1994): 551-6
  24. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  25. Larochelle P, Haynes B, Maron N, Dugas S "A postmarketing surveillance evaluation of quinapril in 3742 canadian hypertensive patients - the ACCEPT study." Clin Ther 16 (1994): 838-53
  26. Schmitt JK, Koch KS, Midha M "Profound hypotension in a tetraplegic patient following angiotensin-converting enzyme inhibitor lisinopril. case report." Paraplegia 32 (1994): 871-4
  27. "Product Information. Univasc (moexipril)." Schwarz Pharma (2001):
  28. Antonios TFT, Macgregor GA "Angiotensin converting enzyme inhibitors in hypertension: potential problems." J Hypertens 13 Suppl (1995): s11-6
  29. Alderman CP "Adverse effects of the angiotensin-converting enzyme inhibitors." Ann Pharmacother 30 (1996): 55-61
  30. "Product Information. Mavik (trandolapril)." Knoll Pharmaceutical Company (2001):
  31. Kaplan NM "The CARE study: a postmarketing evaluation of ramipril in 11,100 patients." Clin Ther 18 (1996): 658-70
  32. Howes LG, Nguyen T, Jackson B "Safety and efficacy of quinapril in hypertensive geriatric patients." J Am Geriatr Soc 44 (1996): 1135

• 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

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  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
  41. Beling S, Vukovich RA, Neiss ES, Zisblatt M, Webb E, Losi M "Long-term experience with indapamide." Am Heart J 106 (1983): 258-62
  42. Slotkoff L "Clinical efficacy and safety of indapamide in the treatment of edema." Am Heart J 106 (1983): 233-7
  43. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc (2002):
  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
  48. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc (2001):
  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
  60. 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
  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):

  Show all 9 sourcesShow fewer sources

  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

  Show all 36 sourcesShow fewer sources

  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

• Hepatic Insufficiency

  Moderate

  The bioavailability of perindoprilat, the active moiety of perindopril is increased in patients with impaired hepatic function. Plasma concentrations of perindoprilat in patients with impaired liver function were about 50% higher than those observed in healthy subjects or hypertensive patients with normal liver function. Caution should be exercised when using perindopril in these patients.

  1 source

  1. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc (2001):

• 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):

  Show all 23 sourcesShow fewer sources

  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.

  27 sources

  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

  With the exception of fosinopril, ACE inhibitors (and/or their active metabolites in some cases) are primarily eliminated by the kidney and may accumulate in patients with renal impairment. ACE inhibitors can also worsen renal function in some patients by blocking the effect of angiotensin II-mediated efferent arteriolar vasoconstriction, thereby decreasing glomerular filtration. Therapy with ACE inhibitors should be administered cautiously in patients with preexisting renal dysfunction, particularly those with renovascular disease. Patients with moderate to severe renal impairment usually require lower or less frequent doses and smaller increments in dose. In addition, a dosage reduction or discontinuation of any concomitantly administered diuretics may be helpful. Fosinopril probably does not require dosage adjustments unless hepatic function is also significantly impaired. In patients with bilateral renal artery stenosis or renal artery stenosis in a solitary kidney, ACE inhibitors may reduce renal perfusion to a critically low level. Renal function should be monitored closely for the first few weeks of therapy.

  32 sources

  1. Schwartz D, Averbuch M, Pines A, et al. "Renal toxicity of enalapril in very elderly patients with progressive, severe congestive heart failure." Chest 100 (1991): 1558-61
  2. Forette B, Koen R, Vivaut E "Efficacy and safety of quinapril in the elderly hypertensive patient." Am Heart J 123 (1992): 1426-32
  3. Ljungman S, Kjekshus J, Swedberg K "Renal function in severe congestive heart failure during treatment with enalapril." Am J Cardiol 70 (1992): 479-87
  4. Thind GS "Renal insufficiency during angiotensin-converting enzyme inhibitor therapy in hypertensive patients with no renal artery stenosis." J Clin Hypertens 1 (1985): 337-43
  5. Champ JD "Case report: azotemia secondary to enalapril and diuretic use and the diagnosis of renovascular hypertension." Am J Med Sci 305 (1993): 25-7
  6. Inman WH, Rawson NS, Wilton LV, et al. "Postmarketing surveillance of enalapril. I: results of prescription-event monitoring." Br Med J 297 (1988): 826-9
  7. O'Donnell D "Renal failure due to enalapril and captopril in bilateral renal artery stenosis: greater awareness needed." Med J Aust 148 (1988): 525-7
  8. Heeg JE, de Jong PE, de Zeeuw D "Lisinopril and renal failure ." Lancet 1 (1989): 846

  Show all 32 sourcesShow fewer sources

  9. Thomson AH, Kelly JG, Whiting B "Lisinopril population pharmacokinetics in elderly and renal disease patients with hypertension." Br J Clin Pharmacol 27 (1989): 57-65
  10. Sica DA, Cutler RE, Parmer RJ, Ford NF "Comparison of the steady-state pharmacokinetics of fosinopril, lisinopril and enalapril in patients with chronic renal insufficiency." Clin Pharmacokinet 20 (1991): 420-7
  11. Knapp LE, Frank GJ, McLain R, Rieger MM, Posvar E, Singer R "The safety and tolerability of quinapril." J Cardiovasc Pharmacol 15 (1990): s47-55
  12. Heintz B, Verho M, Brockmeier D, Kirsten R, Nelson K, Maigatter S, Lefevre G, Kierdorf H, Sieberth HG "Influence of ramipril on renal function in patients with chronic congestive heart failure." J Cardiovasc Pharmacol 18 (1991): s174-9
  13. Dietz R, Nagel F, Osterziel KJ "Angiotensin-converting enzyme inhibitors and renal function in heart failure." Am J Cardiol 70 (1992): c119-25
  14. Frank GJ, Knapp LE, McLain RW "Overall tolerance and safety of quinapril in clinical trials." Angiology 40 (1989): 405-15
  15. Cetnarowski-Cropp AB "Quinapril: a new second-generation ACE inhibitor." DICP 25 (1991): 499-504
  16. Frank GJ, Knapp LE, Olson SC, Phelps MC, Quade MM, Rieger MM, Sedman AJ "Overview of quinapril, a new ACE inhibitor." J Cardiovasc Pharmacol 15 (1990): s14-23
  17. Murray BM, Venuto RC, Kohli R, Cunningham EE "Enalapril-associated acute renal failure in renal transplants: possible role of cyclosporine." Am J Kidney Dis 16 (1990): 66-9
  18. "Product Information. Lotensin (benazepril)." Ciba-Geigy Pharmaceuticals (2002):
  19. "Product Information. Vasotec (enalapril)." Merck & Co., Inc (2002):
  20. "Product Information. Prinivil (lisinopril)." Merck & Co., Inc (2002):
  21. "Product Information. Accupril (quinapril)." Parke-Davis (2001):
  22. "Product Information. Monopril (fosinopril)." Bristol-Myers Squibb (2001):
  23. "Product Information. Altace (ramipril)." Hoechst Marion Roussel (2001):
  24. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc (2001):
  25. "Product Information. Univasc (moexipril)." Schwarz Pharma (2001):
  26. "Moexipril: another ace inhibitor for hypertension." Med Lett Drugs Ther 37 (1995): 75-6
  27. Antonios TFT, Macgregor GA "Angiotensin converting enzyme inhibitors in hypertension: potential problems." J Hypertens 13 Suppl (1995): s11-6
  28. Alderman CP "Adverse effects of the angiotensin-converting enzyme inhibitors." Ann Pharmacother 30 (1996): 55-61
  29. "Product Information. Mavik (trandolapril)." Knoll Pharmaceutical Company (2001):
  30. Persson B, Stimpel M "Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients." Eur J Clin Pharmacol 50 (1996): 259-64
  31. Howes LG, Nguyen T, Jackson B "Safety and efficacy of quinapril in hypertensive geriatric patients." J Am Geriatr Soc 44 (1996): 1135
  32. Olivier PB, German ML, Carette BD, Millart HG, Trenque TC "Elevation of serum creatinine following fosinopril therapy." Ann Pharmacother 33 (1999): 382-3

• Liver Diseases

  Moderate

  Rarely, elevations of liver enzymes and/or serum bilirubin have occurred with the use of ACE inhibitors. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

  10 sources

  1. "Product Information. Lotensin (benazepril)." Ciba-Geigy Pharmaceuticals (2002):
  2. "Product Information. Capoten (captopril)." Bristol-Myers Squibb (2002):
  3. "Product Information. Vasotec (enalapril)." Merck & Co., Inc (2002):
  4. "Product Information. Prinivil (lisinopril)." Merck & Co., Inc (2002):
  5. "Product Information. Accupril (quinapril)." Parke-Davis (2001):
  6. "Product Information. Monopril (fosinopril)." Bristol-Myers Squibb (2001):
  7. "Product Information. Altace (ramipril)." Hoechst Marion Roussel (2001):
  8. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc (2001):

  Show all 10 sourcesShow fewer sources

  9. "Product Information. Univasc (moexipril)." Schwarz Pharma (2001):
  10. "Product Information. Mavik (trandolapril)." Knoll Pharmaceutical Company (2001):

• 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 Perindopril + Indapamide, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.

• angiotensin converting enzyme in

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

  Example product in the source data (US market): Captopril/hydrochlorothiazide

• angiotensin converting enzyme in

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

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

• angiotensin converting enzyme in

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

  Example product in the source data (US market): Trandolapril/verapamil

• angiotensin converting enzyme in

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

  Example product in the source data (US market): Monopril hct

• angiotensin converting enzyme in

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

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

• angiotensin converting enzyme in

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

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

• angiotensin converting enzyme in

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

  Example product in the source data (US market): Lotensin hct

• angiotensin converting enzyme in

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

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

• angiotensin converting enzyme in

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

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

• 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): Ziac

• 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): Captopril/hydrochlorothiazide

• 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): Hydrochlorothiazide/quinapril

• 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): Amturnide

• 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): Amlodipine/hydrochlorothiazide/olmesartan

• 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): Hydrochlorothiazide/metoprolol

• 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): Exforge hct

• 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): Hydrochlorothiazide/propranolol

• 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): Monopril hct

• 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): Hydrochlorothiazide/timolol

• 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): Vaseretic

• 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): Uniretic

• 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): Lotensin hct

• 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

• 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): Hydralazine/hydrochlorothiazide/reserpine

• 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): Prinzide

• 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): Hydralazine/hydrochlorothiazide