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Drug Interactions between Aldactazide and Cozaar

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

spironolactone losartan

Applies to: Aldactazide (hydrochlorothiazide / spironolactone) and Cozaar (losartan)

MONITOR CLOSELY: Concomitant use of angiotensin II receptor blockers (ARBs) and potassium-sparing diuretics may increase the risk of hyperkalemia. Inhibition of angiotensin II results in decreased aldosterone secretion, which can lead to increases in serum potassium that may be additive with that induced by potassium-sparing diuretics. Life-threatening and fatal hyperkalemia can occur, especially when the combination is used in patients with risk factors such as renal impairment, diabetes, old age, severe or worsening heart failure, dehydration, and concomitant use of other agents that block the renin-angiotensin-aldosterone system or otherwise increase serum potassium levels. Individually, both ARBs and potassium-sparing diuretics have been associated with hyperkalemia in patients with renal impairment. ARBs may also cause deterioration of renal function in patients with chronic heart failure, and the risk is increased if they are sodium-depleted or dehydrated secondary to excessive diuresis. A retrospective analysis of the incidence of hyperkalemia in the CHARM study (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) found that the addition of candesartan to standard medical therapy for heart failure was associated with a 2- to 3-fold increase in risk of hyperkalemia, which was further amplified by cotreatment with spironolactone or ACE inhibitors.

MANAGEMENT: Caution is advised if angiotensin II receptor blockers must be used concurrently with potassium-sparing diuretics, particularly in patients with renal impairment, diabetes, old age, severe or worsening heart failure, dehydration, or concomitant therapy with other agents that increase serum potassium such as nonsteroidal anti-inflammatory drugs, beta-blockers, cyclosporine, heparin, tacrolimus, and trimethoprim. Serum potassium and renal function should be checked prior to initiating therapy and regularly thereafter, and potassium supplementation as well as the use of potassium-containing salt substitutes should be avoided unless absolutely necessary and the benefits outweigh the potential risks. Patients should be given counseling on the appropriate levels of potassium and fluid intake, and advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as nausea, vomiting, weakness, listlessness, tingling of the extremities, paralysis, confusion, weak pulse, and a slow or irregular heartbeat. If spironolactone is prescribed with an ARB, some investigators recommend that its dosage not exceed 25 mg/day in high-risk patients.

References

  1. Walmsley RN, White GH, Cain M, McCarthy PJ, Booth J "Hyperkalemia in the elderly." Clin Chem 30 (1984): 1409-12
  2. McNay JL, Oran E "Possible predisposition of diabetic patients to hyperkalemia following administration of potassium-retaining diuretic, amiloride (MK 870)." Metabolism 19 (1970): 58-70
  3. Lawson DH, O'Connor PC, Jick H "Drug attributed alterations in potassium handling in congestive cardiac failure." Eur J Clin Pharmacol 23 (1982): 21-5
  4. "Product Information. Midamor (amiloride)." Merck & Co., Inc PROD (2001):
  5. "Product Information. Cozaar (losartan)." Merck & Co., Inc PROD (2001):
  6. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals PROD (2001):
  7. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals PROD (2001):
  8. Obialo CI, Ofili EO, Mirza T "Hyperkalemia in congestive heart failure patients aged 63 to 85 years with subclinical renal disease." Am J Cardiol 90 (2002): 663-5
  9. Bozkurt B, Agoston I, Knowlton AA "Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines." J Am Coll Cardiol 41 (2003): 211-4
  10. Wrenger E, Muller R, Moesenthin M, Welte T, Frolich JC, Neumann KH "Interaction of spironolactone with ACE inhibitors or angiotensin receptor blockers: analysis of 44 cases." BMJ 327 (2003): 147-9
  11. Jarman PR, Mather HM "Diabetes may be independent risk factor for hyperkalaemia." BMJ 327 (2003): 812
  12. Svensson M, Gustafsson F, Galatius S, Hildebrandt PR, Atar D "Hyperkalaemia and impaired renal function in patients taking spironolactone for congestive heart failure: retrospective study." BMJ 327 (2003): 1141-2
  13. "Spironolactone + ace inhibitor or sartan: risk of hyperkalaemia." Prescrire Int 13 (2004): 58
  14. McMurray JJ, O'Meara E "Treatment of heart failure with spironolactone--trial and tribulations." N Engl J Med 351 (2004): 526-8
  15. Tamirisa KP, Aaronson KD, Koelling TM "Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure." Am Heart J 148 (2004): 971-8
  16. Masoudi FA, Gross CP, Wang Y, et al. "Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States, 1998-2001." Circulation 112 (2005): 39-47
  17. Marcy TR, Ripley TL "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm 63 (2006): 49-58
  18. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  19. Desai AS, Swedberg K, McMurray JJ, et al. "Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program." J Am Coll Cardiol 50 (2007): 1959-66
  20. Perazella MA "Drug-induced hyperkalemia: old culprits and new offenders." Am J Med 109 (2000): 307-14
  21. Fujii H, Nakahama H, Yoshihara F, Nakamura S, Inenaga T, Kawano Y "Life-threatening hyperkalemia during a combined therapy with the angiotensin receptor blocker candesartan and spironolactone." Kobe J Med Sci 51 (2005): 1-6
  22. Jarman PR, Kehely AM, Mather HM "Hyperkalaemia in diabetes: prevalence and associations." Postgrad Med J 71 (1995): 551-2
  23. Perazella MA, Mahnensmith RL "Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis." J Gen Intern Med 12 (1997): 646-56
  24. Large DM, Carr PH, Laing I, Davies M "Hyperkalaemia in diabetes mellitus--potential hazards of coexisting hyporeninaemic hypoaldosteronism." Postgrad Med J 60 (1984): 370-3
View all 24 references

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Drug and food interactions

Moderate

losartan food

Applies to: Cozaar (losartan)

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

MANAGEMENT: 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.

MONITOR: Grapefruit juice may modestly decrease and delay the conversion of losartan to its active metabolite, E3174. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who regularly consume grapefruits and grapefruit juice should be monitored for altered efficacy of losartan. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

References

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc PROD (2001):
  2. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit 23 (2001): 369-73
  3. Ray K, Dorman S, Watson R "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens 13 (1999): 717-20

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Moderate

hydroCHLOROthiazide food

Applies to: Aldactazide (hydrochlorothiazide / spironolactone)

MONITOR: 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.

MANAGEMENT: 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.

References

  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
View all 8 references

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Moderate

spironolactone food

Applies to: Aldactazide (hydrochlorothiazide / spironolactone)

MONITOR: 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.

MANAGEMENT: 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.

References

  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
View all 8 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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