Amlodipine Besilate + Valsartan interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

  What to do: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

  8 sources

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595

• alcohol

  Moderate

  Synergy

  Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

  What to do: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

  8 sources

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595

• Food High in Potassium

  Moderate

  Synergy

  Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion.

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

  2 sources

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

• 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 Amlodipine Besilate + Valsartan needs care, as documented in this source.

• Angioedema

  Major

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

  8 sources

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

• 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

• Diabetes Mellitus

  Major

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

  7 sources

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

• Hypotension

  Major

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

  27 sources

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

  Show all 27 sourcesShow fewer sources

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

• 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):

• 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

• Heart Failure

  Moderate

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

  28 sources

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

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

• 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.

  29 sources

  1. Gillmer DJ, Kark P "Pulmonary oedema precipitated by nifedipine." Br Med J 280 (1980): 1420-1
  2. Batra AK, Segall PH, Ahmed T "Pulmonary edema with nifedipine in primary pulmonary hypertension." Respiration 47 (1985): 161-3
  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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  9. Yedinak KC, Lopez LM "Felodipine: a new dihydropyridine calcium-channel antagonist." DICP 25 (1991): 1193-206
  10. Lorimer AR, Pringle SD "The safety of felodipine." J Cardiovasc Pharmacol 15 (1990): s85-9
  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
  13. "Product Information. Norvasc (amlodipine)." Pfizer U.S. Pharmaceuticals (2002):
  14. "Product Information. Plendil (felodipine)." Merck & Co., Inc (2002):
  15. "Product Information. Cardene (nicardipine)." Syntex Laboratories Inc (2002):
  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
  25. "Product Information. Sular (nisoldipine)." Astra-Zeneca Pharmaceuticals (2001):
  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

• Hyperkalemia

  Moderate

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

  8 sources

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

• Kidney Diseases

  Moderate

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

  8 sources

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

• Liver Diseases

  Moderate

  Valsartan is primarily eliminated by biliary excretion, and a minority is excreted in the urine. Dosage adjustments are not necessary in patients with renal impairment unless they are also volume-depleted, in which case therapy should be initiated under medical supervision. Likewise, patients with mild to moderate hepatic impairment or biliary obstruction generally do not require a dosage adjustment. The manufacturer recommends administering valsartan therapy with caution in patients with impaired renal and/or liver function, particularly if these conditions are severe.

  1 source

  1. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):

• Renal Artery Obstruction

  Moderate

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

  8 sources

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

Therapeutic duplication

Drug classes that overlap with Amlodipine Besilate + Valsartan, 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