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Drug Interactions between Percodan and ramipril

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

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Interactions between your drugs

Moderate

aspirin ramipril

Applies to: Percodan (aspirin / oxycodone) and ramipril

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

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Moderate

oxyCODONE ramipril

Applies to: Percodan (aspirin / oxycodone) and ramipril

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

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Drug and food interactions

Major

oxyCODONE food

Applies to: Percodan (aspirin / oxycodone)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including oxycodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of oxycodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of oxycodone by certain compounds present in grapefruit, resulting in decreased formation of metabolites noroxycodone and noroxymorphone and increased formation of oxymorphone due to a presumed shifting of oxycodone metabolism towards the CYP450 2D6-mediated route. In 12 healthy, nonsmoking volunteers, administration of a single 10 mg oral dose of oxycodone hydrochloride on day 4 of a grapefruit juice treatment phase (200 mL three times a day for 5 days) increased mean oxycodone peak plasma concentration (Cmax), systemic exposure (AUC) and half-life by 48%, 67% and 17% (from 3.5 to 4.1 hours), respectively, compared to administration during an equivalent water treatment phase. Grapefruit juice also decreased the metabolite-to-parent AUC ratio of noroxycodone by 44% and that of noroxymorphone by 45%. In addition, oxymorphone Cmax and AUC increased by 32% and 56%, but the metabolite-to-parent AUC ratio remained unchanged. Pharmacodynamic changes were modest and only self-reported performance was significantly impaired after grapefruit juice. Analgesic effects were not affected.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with oxycodone. Any history of alcohol or illicit drug use should be considered when prescribing oxycodone, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with oxycodone may also want to avoid or limit the consumption of grapefruit and grapefruit juice.

References

  1. Nieminen TH, Hagelberg NM, Saari TI, et al. (2010) "Grapefruit juice enhances the exposure to oral oxycodone." Basic Clin Pharmacol Toxicol, 107, p. 782-8

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Moderate

ramipril food

Applies to: ramipril

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

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Moderate

aspirin food

Applies to: Percodan (aspirin / oxycodone)

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

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Moderate

ramipril food

Applies to: ramipril

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

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Minor

aspirin food

Applies to: Percodan (aspirin / oxycodone)

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 (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 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.