Drug Interaction Report

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.

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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.

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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.

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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.

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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.

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