Drug Interactions between Demi-Cof and Zestril

MONITOR CLOSELY: Concomitant use of angiotensin converting enzyme (ACE) inhibitors and potassium salts may increase the risk of hyperkalemia. Inhibition of ACE results in decreased aldosterone secretion, which in turn causes potassium retention. In one report, a significant increase in serum potassium level (3.88 +/- 0.41 to 4.84 +/- 0.45 mEq/L) was observed within one or two days following the addition of captopril in five patients who were treated with regimens that included potassium supplements or potassium-sparing diuretics. Three patients had laboratory-diagnosed hyperkalemia, including one patient receiving potassium supplementation who had a 66% increase in serum potassium. Levels remained elevated until potassium supplementation or captopril therapy was reduced or discontinued. In a postmarketing survey of patients who were prescribed enalapril in England between April and December 1985, researchers identified ten cases where enalapril appeared to have contributed to a deterioration in renal function and subsequent death. All ten patients had hyperkalemia, and seven were also receiving moderate to high dosages of potassium-sparing diuretics and/or potassium supplements. Hyperkalemia was felt to be the immediate cause of death in two of them. Risk factors for developing severe or life-threatening hyperkalemia may include 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.

MANAGEMENT: Caution is advised if ACE inhibitors must be used concurrently with potassium salts, 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, trimethoprim, and licorice. The combination should generally be avoided in these patients unless absolutely necessary and the benefits outweigh the potential risks. Serum potassium and renal function should be checked prior to initiating therapy and regularly thereafter. 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.

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MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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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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