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Drug Interactions between Ache and Pain Relief to Go and Lotensin HCT

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

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Moderate

aspirin benazepril

Applies to: Ache and Pain Relief to Go (aspirin / caffeine) and Lotensin HCT (benazepril / hydrochlorothiazide)

MONITOR: Some investigators suggest that coadministration with aspirin may attenuate the vasodilator and hypotensive effects of ACE inhibitors. In addition, some have found that the benefits of ACE inhibitors on morbidity and mortality in post-acute myocardial infarction, coronary heart disease, and particularly congestive heart failure may be compromised or even nullified by aspirin. The proposed mechanism is aspirin inhibition of cyclooxygenase, resulting in suppression of prostaglandin synthesis and prostaglandin-mediated hemodynamic effects of ACE inhibitors. However, evidence of a negative interaction is largely contradictory, and interpretation of relevant data has often been complicated by multiple confounding elements as well as the retrospective or post hoc nature of most studies. Available data seem to indicate that low-dose aspirin (less than 236 mg/day, and especially less than 100 mg/day) is unlikely, or at least significantly less likely, to interfere with ACE inhibitor effects, although susceptibility to the interaction may be subject to some degree of interpatient variability.

MANAGEMENT: Based on current data, it is difficult to determine the likelihood of a negative interaction between aspirin and ACE inhibitors and its clinical relevance during long-term therapy, particularly in congestive heart failure. Current recommendations generally do not preclude combination use in patients with cardiovascular diseases or risk factors that might otherwise benefit from the drugs independently. However, patients receiving long-term therapy with the combination should undergo regular blood pressure and other appropriate clinical monitoring such as renal function assessments. The lowest therapeutic dosage of aspirin should be used.

References

  1. Moore TJ, Crantz FR, Hollenberg NK "Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension." Hypertension 3 (1981): 168-73
  2. Silberbauer K, Stanek B, Templ H "Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition." Br J Clin Pharmacol 14 (1982): s87-93
  3. Pfeffer MA, Braunwald E, Moye LA, et al. "Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial." N Engl J Med 327 (1992): 669-77
  4. Hall D, Zeitler H, Rudolph W "Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure." J Am Coll Cardiol 20 (1992): 1549-55
  5. Acute Infarction Ramipril Efficacy (AIRE) Study Investigators "Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure." Lancet 342 (1993): 821-8
  6. Polonia J, Boaventura I, Gama G, Camoes I, Bernardo F, Andrade P, Nunes JP, Brandao F, Cerqueiragomes M "Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients." J Hypertens 13 (1995): 925-31
  7. Kober L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K, Videbaek J, Cole DS, Auclert L, Pauly NC, et al. "A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group." N Engl J Med 333 (1995): 1670-6
  8. Nguyen KN, Aursnes I, Kjekshus J "Interaction between enalapril and aspirin on mortality after acute myocardial infarction: subgroup analysis of the cooperative new scandinavian enalapril survival study II (CONSENSUS II)." Am J Cardiol 79 (1997): 115-9
  9. Oosterga M, Anthonio RL, deKam PJ, Kingma JH, Crijns HJGM, vanGilst WH "Effects of aspirin on angiotensin-converting enzyme inhibition and left ventricular dilation one year after acute myocardial infarction." Am J Cardiol 81 (1998): 1178-81
  10. Spaulding C, Charbonnier B, CohenSolal A, Juilliere Y, Kromer EP, Benhamda K, Cador R, Weber S "Acute hemodynamic interaction of aspirin and ticlopidine with enalapril: Results of a double-blind, randomized comparative trial." Circulation 98 (1998): 757-65
  11. Song KH, Fedyk R, Hoover R "Interaction of ACE inhibitors and aspirin in patients with congestive heart failure." Ann Pharmacother 33 (1999): 375-7
  12. Leor J, ReicherReiss H, Goldbourt U, Boyko V, Gottlieb S, Battler A, Behar S "Aspirin and mortality in patients treated with angiotensin-converting enzyme inhibitors - A cohort study of 11,575 patients with coronary artery disease." J Am Coll Cardiol 33 (1999): 1920-5
  13. The Heart Outcomes Prevention Evaluation Study Investigators "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients." N Engl J Med 342 (2000): 145-53
  14. Massie BM, Teerlink JR "Interaction between aspirin and angiotensin-converting enzyme inhibitors: Real or imagined." Am J Med 109 (2000): 431-3
  15. Meune C, Mahe I, Mourad JJ, Simoneau G, Knellwolf AL, Bergmann JF, Caulin C "Interaction between angiotensin-converting enzyme inhibitors and aspirin: a review." Eur J Clin Pharmacol 56 (2000): 609-20
  16. Mahe I, Meune C, Diemer M, Caulin C, Bergmann JF "Interaction between aspirin and ACE inhibitors in patients with heart failure." Drug Saf 24 (2001): 167-82
  17. Zanchetti A, Hansson L, Leonetti G, et al. "Low-dose aspirin does not interfere with the blood pressure-lowering effects of antihypertensive therapy." J Hypertens 20 (2002): 1015-1022
  18. Ahmed A "Interaction between aspirin and angiotensin-converting enzyme inhibitors: should they be used together in older adults with heart failure?" J Am Geriatr Soc 50 (2002): 1293-6
  19. Lapane KL, Hume AL, Barbour MM, Lipsitz LA "Does aspirin attenuate the effect of angiotensin-converting enzyme inhibitors on health outcomes of very old patients with heart failure?" J Am Geriatr Soc 50 (2002): 1198-204
  20. Nawarskas JJ, Spinler SA "Update on the interaction between aspirin and angiotensin-converting enzyme inhibitors." Pharmacotherapy 20 (2000): 698-710
  21. Nawarskas JJ, Spinler SA "Does aspirin interfere with the therapeutic efficacy of angiotensin-converting enzymen inhibitors in hypertension or congestive heart failure?" Pharmacotherapy 18 (1998): 1041-52
  22. Teo K, Yusuf S, Pfeffer M, et al. "Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review." Lancet 360 (2002): 1037
  23. Guazzi M, Brambilla R, Reina G, Tumminello G, Guazzi MD "Aspirin-angiotensin-converting enzyme inhibitor coadministration and mortality in patients with heart failure: a dose-related adverse effect of aspirin." Arch Intern Med 163 (2003): 1574-9
View all 23 references

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Moderate

hydroCHLOROthiazide benazepril

Applies to: Lotensin HCT (benazepril / hydrochlorothiazide) and Lotensin HCT (benazepril / hydrochlorothiazide)

MONITOR: Although they are frequently combined in clinical practice, diuretics and angiotensin converting enzyme (ACE) inhibitors may have additive effects. Coadministration makes hypotension and hypovolemia more likely than does either drug alone. Some ACE inhibitors may attenuate the increase in the urinary excretion of sodium caused by some loop diuretics. Some patients on diuretics, especially those on dialysis or a dietary salt restriction, may experience acute hypotension with lightheadedness and dizziness after receiving the first dose of the ACE inhibitor. In addition, ACE inhibitors may cause renal insufficiency or acute renal failure in patients with sodium depletion or renal artery stenosis.

MANAGEMENT: Monitoring of blood pressure, diuresis, electrolytes, and renal function is recommended during coadministration. The possibility of first-dose hypotensive effects may be minimized by initiating therapy with small doses of the ACE inhibitor, or either discontinuing the diuretic temporarily or increasing the salt intake approximately one week prior to initiating an ACE inhibitor. Alternatively, the patient may remain under medical supervision for at least two hours after the first dose of the ACE inhibitor, or until blood pressure has stabilized.

References

  1. Reader C, Peyregne EA, Suarez LD "Amrinone therapy in congestive cardiomyopathy." Am Heart J 105 (1983): 1045
  2. Fujimura A, Shimokawa Y, Ebihara A "Influence of captopril on urinary excretion of furosemide in hypertensive subjects." J Clin Pharmacol 30 (1990): 538-42
  3. Funck-Brentano C, Chatellier G, Alexandre JM "Reversible renal failure after combined treatment with enalapril and furosemide in a patient with congestive heart failure." Br Heart J 55 (1986): 596-8
  4. Weisser K, Schloos J, Jakob S, et al. "The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients." Eur J Clin Pharmacol 43 (1992): 173-7
  5. Motwani JG, Fenwick MK, Morton JJ, Struthers AD "Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure." Circulation 86 (1992): 439-45
  6. Burnakis TG, Mioduch HJ "Combined therapy with captopril and potassium supplementation: a potential for hyperkalemia." Arch Intern Med 144 (1984): 2371-2
  7. Murphy BF, Whitworth JA, Kincaid-Smith P "Renal insufficiency with combinations of angiotensin converting enzyme inhibitors and diuretics." Br Med J 288 (1984): 844-5
  8. Thind GS "Renal insufficiency during angiotensin-converting enzyme inhibitor therapy in hypertensive patients with no renal artery stenosis." J Clin Hypertens 1 (1985): 337-43
  9. Radley AS, Fitzpatrick RW "An evaluation of the potential interaction between enalapril and amiloride." J Clin Pharm Ther 12 (1987): 319-23
  10. Champ JD "Case report: azotemia secondary to enalapril and diuretic use and the diagnosis of renovascular hypertension." Am J Med Sci 305 (1993): 25-7
  11. Hume AL, Murphy JL, Lauerman SE "Angiotensin-converting enzyme inhibitor-induced cough." Pharmacotherapy 9 (1989): 88-90
  12. Lee HB, Blaufox MD "Renal functional response to captopril during diuretic therapy." J Nucl Med 33 (1992): 739-43
  13. DeQuattro V "Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide." Clin Cardiol 14 (1991): iv28-32;
  14. "Product Information. Vasotec (enalapril)." Merck & Co., Inc PROD (2002):
  15. McLay JS, McMurray JJ, Bridges AB, Fraser CG, Struthers AD "Acute effects of captopril on the renal actions of furosemide in patients with chronic heart failure." Am Heart J 126 (1993): 879-86
  16. Sudoh T, Fujimura A, Shiga T, et al. "Influence of lisinopril on urinary electrolytes excretion after furosemide in healthy subjects." J Clin Pharmacol 33 (1993): 640-3
  17. Lederle RM "Captopril and hydrochlorothiazide in the fixed combination multicenter trial." J Cardiovasc Pharmacol 7 (1985): S63-9
  18. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc PROD (2001):
  19. Good JM, Brady AJ, Noormohamed FH, Oakley CM, Cleland JG "Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition." Circulation 90 (1994): 220-4
  20. "Product Information. Capoten (captopril)." Bristol-Myers Squibb PROD (2001):
  21. "Product Information. Lexxel (enalapril-felodipine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  22. "Product Information. Zestril (lisinopril)." Astra-Zeneca Pharmaceuticals PROD
  23. Cerner Multum, Inc. "Australian Product Information." O 0
View all 23 references

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Minor

aspirin caffeine

Applies to: Ache and Pain Relief to Go (aspirin / caffeine) and Ache and Pain Relief to Go (aspirin / caffeine)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 71-6

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Drug and food interactions

Moderate

benazepril food

Applies to: Lotensin HCT (benazepril / hydrochlorothiazide)

GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

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

References

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

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Moderate

aspirin food

Applies to: Ache and Pain Relief to Go (aspirin / caffeine)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):

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Moderate

hydroCHLOROthiazide food

Applies to: Lotensin HCT (benazepril / hydrochlorothiazide)

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

benazepril food

Applies to: Lotensin HCT (benazepril / hydrochlorothiazide)

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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Minor

caffeine food

Applies to: Ache and Pain Relief to Go (aspirin / caffeine)

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy 16 (1996): 1046-52

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Minor

aspirin food

Applies to: Ache and Pain Relief to Go (aspirin / caffeine)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 71-6

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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