Indapamide + Amlodipine 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

• grapefruit juice

  Minor

  Metabolism

  The consumption of grapefruit juice may slightly increase plasma concentrations of amlodipine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

  What to do: Concomitant use of Amlodipine with grapefruit or grapefruit juice should generally be avoided.

  6 sources

  1. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  2. Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93
  3. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  4. Vincent J, Harris SI, Foulds G, Dogolo LC, Willavize S, Friedman HL "Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine." Br J Clin Pharmacol 50 (2000): 455-63
  5. Josefsson M, Ahlner J "Amlodipine and grapefruit juice." Br J Clin Pharmacol 53 (2002): 405; discussion 406
  6. Kane GC, Lipsky JJ "Drug-grapefruit juice interactions." Mayo Clin Proc 75 (2000): 933-42

Conditions

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

• 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.

• Coronary Artery Disease

  Major

  Increased frequency, duration, and/or severity of angina, as well as acute myocardial infarction, have rarely developed during initiation or dosage increase of calcium channel blockers (CCBs), particularly in patients with severe obstructive coronary artery disease and those treated with immediate-release formulations. The mechanism of this effect is not established. Therapy with CCBs should be administered cautiously in patients with significant coronary artery disease.

  15 sources

  1. Schanzenbacher P, Deeg P, Liebau G, Kochsiek K "Paradoxical angina after nifedipine: angiographic documentation." Am J Cardiol 53 (1984): 345-6
  2. Manga P, Vythilingum "Unstable angina precipitated by nifedipine." S Afr Med J 66 (1984): 144
  3. Sia STB, MacDonald PS, Triester B, et al. "Aggravation of myocardial ischaemia by nifedipine." Med J Aust 142 (1985): 48-50
  4. Myrhed M, Wiholm B-E "Nifedipine: a survey of adverse effects." Acta Pharmacol Toxicol (Copenh) 58 (1986): 133-6
  5. Lambert CR, Hill JA, Feldman RL, Pepine CJ "Myocardial ischemia during intravenous nicardipine administration." Am J Cardiol 55 (1985): 844-5
  6. Thomassen AR, Bagger JP, Nielsen TT "Hemodynamic and cardiac metabolic changes during nicardipine-induced myocardial ischemia." Cathet Cardiovasc Diagn 14 (1988): 41-3
  7. "Product Information. Norvasc (amlodipine)." Pfizer U.S. Pharmaceuticals (2002):
  8. "Product Information. Cardene (nicardipine)." Syntex Laboratories Inc (2002):

  Show all 15 sourcesShow fewer sources

  9. "Product Information. Procardia (nifedipine)." Pfizer U.S. Pharmaceuticals (2002):
  10. Furberg CD, Psaty BM, Meyer JV "Nifedipine: dose-related increase in mortality in patients with coronary heart disease." Circulation 92 (1995): 1326-31
  11. Kloner RA "Nifedipine in ischemic heart disease." Circulation 92 (1995): 1074-8
  12. Yusuf S "Calcium antagonists in coronary artery disease and hypertension: time for reevaluation?" Circulation 92 (1995): 1079-82
  13. "Product Information. Sular (nisoldipine)." Astra-Zeneca Pharmaceuticals (2001):
  14. Oei SG, Oei SK, Brolmann HAM "Myocardial infarction during nifedipine therapy for preterm labor." N Engl J Med 340 (1999): 154
  15. Abernathy DR, Schwrtz JB "Calcium-antagonist drugs." N Engl J Med 341 (1999): 1447-57

• 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

  Calcium channel blockers (CCBs) are extensively metabolized by the liver. The half-lives of CCBs may be prolonged substantially in patients with severe hepatic impairment, with the potential for significant drug accumulation. In addition, the use of some CCBs has been associated with elevations in serum transaminases, both with and without concomitant elevations in alkaline phosphatase and bilirubin. While these effects may be transient and reversible, some patients have developed cholestasis or hepatocellular injury. Therapy with CCBs should be administered cautiously and often at reduced dosages in patients with significantly impaired hepatic function. Periodic monitoring of liver function is advised.

  54 sources

  1. Echizen H, Eichelbaum M "Clinical pharmacokinetics of verapamil, nifedipine and diltiazem." Clin Pharmacokinet 11 (1986): 425-49
  2. Saracheck NS, London RL, Matulewicz TJ, et al. "Diltiazem and granulomatous hepatitis." Gastroenterology 88 (1985): 1260-2
  3. Shallcross H, Padley SP, Glynn MJ, Gibbs DD "Fatal renal and hepatic toxicity after treatment with diltiazem." Br Med J 295 (1987): 1256-7
  4. Colombo G, Zucchella G, Planca E, Grieco A "Intravenous diltiazem in the treatment of unstable angina: a study of efficacy and tolerance." Clin Ther 9 (1987): 536-47
  5. Toft E, Vyberg M, Therkelsen K "Diltiazem-induced granulomatous hepatitis." Histopathology 18 (1991): 474-5
  6. Abramson M, Littlejohn GO "Hepatic reactions to nifedipine." Med J Aust 142 (1985): 47-8
  7. Toner M, White A, Moriarty J, Clancy L "Allergic urticarial eruption, leukocytosis and abnormal liver function tests following nifedipine administration." Chest 93 (1988): 1320-1
  8. Babany G, Uzzan F, Larrey D, et al. "Alcoholic-like liver lesions induced by nifedipine." J Hepatol 9 (1989): 252-5

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  9. Brodsky SJ, Cutler SS, Weiner DA, Klein MD "Hepatotoxicity due to treatment with verapamil." Ann Intern Med 94 (1981): 490-1
  10. Somogyi A, Albrecht M, Kliems G, et al. "Pharmacokinetics, bioavailability and ECG response of verapamil in patients with liver cirrhosis." Br J Clin Pharmacol 12 (1981): 51-60
  11. Woodcock BG, Rietbrock I, Vohringer HF, Rietbrock N "Verapamil disposition in liver disease and intensive-care patients: kinetics, clearance, and apparent blood flow relationships." Clin Pharmacol Ther 29 (1981): 27-34
  12. Woodcock BG, Rietbrock N "Verapamil bioavailability and dosage in liver disease." Br J Clin Pharmacol 13 (1982): 240-1
  13. Stern EH, Pitchon R, King BD, Wiener I "Possible hepatitis from verapamil." N Engl J Med 306 (1982): 612-3
  14. Stehle G, Buss J, Eibach J, et al. "Cardiogenic shock associated with verapamil in a patient with liver cirrhosis." Lancet 336 (1990): 1079
  15. Hare DL, Horowitz JD "Verapamil hepatotoxicity: a hypersensitivity reaction." Am Heart J 111 (1986): 610-11
  16. Guarascio P, D'Amato C, Sette P, et al. "Liver damage from verapamil." Br Med J 288 (1984): 362-3
  17. Dow RJ, Graham DJM "A reveiw of the human metabolism and pharmacokinetics of nicardipine hydrochloride." Br J Clin Pharmacol 22 (1986): s195-202
  18. McAllister RG Jr, Hamann SR, Blouin RA "Pharmacokinetics of calcium-entry blockers." Am J Cardiol 55 (1985): b30-40
  19. Kates RE "Calcium antagonists: pharmacokinetic properties." Drugs 25 (1983): 113-24
  20. Finucci GF, Padrini R, Piovan D, et al. "Verapamil pharmacokinetics and liver function in patients with cirrhosis." Int J Clin Pharmacol Res 8 (1988): 123-6
  21. Giacomini KM, Massoud N, Wong FM, Giacomini JC "Decreased binding of verapamil to plasma proteins in patients with liver disease." J Cardiovasc Pharmacol 6 (1984): 924-8
  22. Razak TA, McNeil JJ, Sewell RB, Drummer OH, Smallwood RA, Conway EL, Louis WJ "The effect of hepatic cirrhosis on the pharmacokinetics and blood pressure response to nicardipine." Clin Pharmacol Ther 47 (1990): 463-9
  23. Rush WR, Alexander O, Hall DJ, Cairncross L, Dow RJ, Graham DJ "The metabolism of nicardipine hydrochloride in healthy male volunteers." Xenobiotica 16 (1986): 341-9
  24. Benet LZ "Pharmacokinetics and metabolism of bepridil." Am J Cardiol 55 (1985): c8-13
  25. Kurosawa S, Kurosawa N, Owada E, et al. "Pharmacokinetics of diltiazem in patients with liver cirrhosis." Int J Clin Pharmacol Res 10 (1990): 311-8
  26. Elliott HL, Meredith PA "The clinical consequences of the absorption, distribution, metabolism and excretion of amlodipine." Postgrad Med J 67 (1991): s20-3
  27. Stopher DA, Beresford AP, Macrae PV, Humphrey MJ "The metabolism and pharmacokinetics of amlodipine in humans and animals." J Cardiovasc Pharmacol 12 (1988): s55-9
  28. Kleinbloesem CH, van Harten J, Wilson JP, et al. "Nifedipine: kinetics and hemodynamic effects in patients with liver cirrhosis after intravenous and oral administration." Clin Pharmacol Ther 40 (1986): 21-8
  29. Raemsch KD, Sommer J "Pharmacokinetics and metabolism of nifedipine." Hypertension 5 (1983): 18-24
  30. Ramsch KD, Graefe KH, Scherling D, et al. "Pharmacokinetics and metabolism of calcium-blocking agents nifedipine, nitrendipine, and nimodipine." Am J Nephrol 6 (1986): 73-80
  31. Challenor VF, Waller DG, Renwick AG, et al. "The trans-hepatic extraction of nifedipine." Br J Clin Pharmacol 24 (1987): 473-7
  32. Dunselman PH, Edgar B "Felodipine clinical pharmacokinetics." Clin Pharmacokinet 21 (1991): 418-30
  33. Regardh CG, Edgar B, Olsson R, Kendall M, Collste P, Shansky C "Pharmacokinetics of felodipine in patients with liver disease." Eur J Clin Pharmacol 36 (1989): 473-9
  34. Cotting J, Reichen J, Kutz K, Laplanche R, Nuesch E "Pharmacokinetics of isradipine in patients with chronic liver disease." Eur J Clin Pharmacol 38 (1990): 599-603
  35. Tse FL, Jaffe JM "Pharmacokinetics of PN 200-110 (isradipine), a new calcium antagonist, after oral administration in man." Eur J Clin Pharmacol 32 (1987): 361-5
  36. Graham D, Dow R, Hall D, Alexander O, Mroszczak E, Freedman A "The metabolism and pharmacokinetics of nicardipine hydrochloride in man." Br J Clin Pharmacol 20 (1985): s23-8
  37. Gengo FM, Fagan SC, Krol G, Bernhard H "Nimodipine disposition and haemodynamic effects in patients with cirrhosis and age-matched controls." Br J Clin Pharmacol 23 (1987): 47-53
  38. Meredith P, Elliott H "Clinical pharmacokinetics of amlodipine." Clin Pharmacokinet 22 (1992): 22-31
  39. "Product Information. Norvasc (amlodipine)." Pfizer U.S. Pharmaceuticals (2002):
  40. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical (2002):
  41. "Product Information. Cardizem (diltiazem)." Hoechst Marion Roussel (2002):
  42. "Product Information. Plendil (felodipine)." Merck & Co., Inc (2002):
  43. "Product Information. Cardene (nicardipine)." Syntex Laboratories Inc (2002):
  44. "Product Information. Procardia (nifedipine)." Pfizer U.S. Pharmaceuticals (2002):
  45. "Product Information. Nimotop (nimodipine)." Bayer (2002):
  46. "Product Information. Calan (verapamil)." Searle (2001):
  47. Johnson KE, Balderston SM, Pieper JA, Mann DE, Reiter MJ "Electrophysiologic effects of verapamil metabolites in the isolated heart." J Cardiovasc Pharmacol 17 (1991): 830-7
  48. "Product Information. Dynacirc (isradipine)." Sandoz Pharmaceuticals Corporation
  49. Kumar KL, Colley CA "Verapamil-induced hepatotoxicity." West J Med 160 (1994): 485-6
  50. Traverse JH, Swenson LJ, Mcbride JW "Acute hepatic injury after treatment with diltiazem." Am Heart J 127 (1994): 1636-9
  51. Scherling D, Karl W, Ahr G, Ahr HJ, Wehinger E "Pharmacokinetics of nisoldipine. III. Biotransformation of nisoldipine in rat, dog, monkey, and man." Arzneimittelforschung 38 (1988): 1105-10
  52. "Product Information. Sular (nisoldipine)." Astra-Zeneca Pharmaceuticals (2001):
  53. Abernathy DR, Schwrtz JB "Calcium-antagonist drugs." N Engl J Med 341 (1999): 1447-57
  54. "Product Information. Conjupri (levamlodipine)." CSPC Ouyi Pharmaceutical Co, Ltd (2020):

• 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

• Shock, Cardiogenic

  Major

  In general, calcium channel blockers (CCBs) should not be used in patients with hypotension (systolic pressure < 90 mm Hg) or cardiogenic shock. Due to potential negative inotropic and peripheral vasodilating effects, the use of CCBs may further depress cardiac output and blood pressure, which can be detrimental in these patients. The use of verapamil and diltiazem is specifically contraindicated under these circumstances.

  6 sources

  1. Stehle G, Buss J, Eibach J, et al. "Cardiogenic shock associated with verapamil in a patient with liver cirrhosis." Lancet 336 (1990): 1079
  2. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical (2002):
  3. "Product Information. Cardizem (diltiazem)." Hoechst Marion Roussel (2002):
  4. "Product Information. Calan (verapamil)." Searle (2001):
  5. Kubota K, Pearce GL, Inman WHW "Vasodilation-related adverse events in diltiazem and dihydropyridine calcium antagonists studied by prescription-event monitoring." Eur J Clin Pharmacol 48 (1995): 1-7
  6. Pahor M, Manto A, Pedone C, Carosella L, Guralnik JM, Carbonin P "Age and severe adverse drug reactions caused by nifedipine and verapamil." J Clin Epidemiol 49 (1996): 921-8

• 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

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  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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  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):

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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.

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  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
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  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

  Calcium channel blockers (CCBs) may have varying degrees of negative inotropic effect. Congestive heart failure (CHF), worsening of CHF, and pulmonary edema have occurred in some patients treated with a CCB, primarily verapamil. Some CCBs have also caused mild to moderate peripheral edema due to localized vasodilation of dependent arterioles and small blood vessels, which can be confused with the effects of increasing left ventricular dysfunction. Although some CCBs have been used in the treatment of CHF, therapy with CCBs should be administered cautiously in patients with severe left ventricular dysfunction (e.g., ejection fraction < 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker. Likewise, caution is advised in patients with acute myocardial infarction and pulmonary congestion documented by X-ray on admission, since associated heart failure may be acutely worsened by administration of a CCB.

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  3. Myrhed M, Wiholm B-E "Nifedipine: a survey of adverse effects." Acta Pharmacol Toxicol (Copenh) 58 (1986): 133-6
  4. Prigogine T, Waterlot Y, Gottignies P, et al. "Acute nonhemodynamic pulmonary edema with nifedipine in primary pulmonary hypertension." Chest 100 (1991): 563-4
  5. Batlouni M, Armaganijan D, Ghorayeb N, Magliano MF "Clinical efficacy and tolerability of isradipine in the treatment of mild-to-moderate hypertension in young and elderly patients." J Cardiovasc Pharmacol 19 (1992): s53-7
  6. Scheidt S, LeWinter MM, Hermanovich J, Venkataraman K, Freedman D "Efficacy and safety of nicardipine for chronic, stable angina pectoris: a multicenter randomized trial." Am J Cardiol 58 (1986): 715-21
  7. Taylor SH, Frais MA, Lee P, Verma SP, Jackson N, Reynolds G, Silke B "A study of the long-term efficacy and tolerability of oral nicardipine in hypertensive patients." Br J Clin Pharmacol 20 (1985): s139-42
  8. Dubois C, Blanchard D "Efficacy and safety of nicardipine in 29,104 patients with hypertension." Clin Ther 11 (1989): 452-60

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  11. Sundstedt CD, Ruegg PC, Keller A, Waite R "A multicenter evaluation of the safety, tolerability, and efficacy of isradipine in the treatment of essential hypertension." Am J Med 86 (1989): 98-102
  12. Ruegg PC, Nelson DJ "Safety and efficacy of isradipine, alone and in combination, in the treatment of angina pectoris." Am J Med 86 (1989): 70-4
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  16. "Product Information. Procardia (nifedipine)." Pfizer U.S. Pharmaceuticals (2002):
  17. "Product Information. Nimotop (nimodipine)." Bayer (2002):
  18. "Product Information. Dynacirc (isradipine)." Sandoz Pharmaceuticals Corporation
  19. Walton T, Symes LR "Felodipine and isradipine: new calcium-channel-blocking agents for the treatment of hypertension." Clin Pharm 12 (1993): 261-75
  20. Fagan TC, Haggert BE, Liss C "Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension." Clin Ther 16 (1994): 634-46
  21. Blecker D "Antihypertensive therapy with isradipine in patients with special safety concerns." Angiology 45 (1994): 997-1008
  22. Brogden RN, Sorkin EM "Isradipine: an update of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of mild to moderate hypertension." Drugs 49 (1995): 618-49
  23. Kubota K, Pearce GL, Inman WHW "Vasodilation-related adverse events in diltiazem and dihydropyridine calcium antagonists studied by prescription-event monitoring." Eur J Clin Pharmacol 48 (1995): 1-7
  24. Johnson BF, Eisner GM, Mcmahon FG, Jain AK, Rudd P, Sowers JR "A multicenter comparison of adverse reaction profiles of isradipine and enalapril at equipotent doses in patients with essential hypertension." J Clin Pharmacol 35 (1995): 484-92
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  26. Sleight P "Calcium antagonists during and after myocardial infarction." Drugs 51 (1996): 216-25
  27. Elkayam U "Calcium channel blockers in heart failure." Cardiology 89 (1998): 38-46
  28. Schaefer RM, Aldons PM, Burgess ED, Tilvis R, Singh GP, Rehn L, Morgan TO "Improved tolerability of felodipine compared with amlodipine in elderly hypertensives: A randomised, double-blind study in 535 patients, focusing on vasodilatory adverse events." Int J Clin Pract 52 (1998): 381
  29. Abernathy DR, Schwrtz JB "Calcium-antagonist drugs." N Engl J Med 341 (1999): 1447-57

• 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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  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

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

• calcium channel blockers

  The recommended maximum number of medicines in the 'calcium channel blockers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'calcium channel blockers' category.

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

• 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