Drug Interactions between Capozide 50/25 and Dual Action Complete

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.

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MONITOR: Coadministration of thiazide diuretics with high dosages of calcium and/or vitamin D has been associated with reports of hypercalcemia in some patients. Thiazide diuretics inhibit the renal excretion of calcium and may also enhance responsiveness of bone and renal tubule to parathyroid hormone, thus concurrent use of large amounts of calcium or vitamin D can lead to excessively high plasma levels of calcium. Patients who are particularly susceptible include those with hyperparathyroidism, those being treated for osteoporosis, and those receiving high dosages of vitamin D for hypoparathyroidism. Metabolic alkalosis and the milk-alkali syndrome have been reported during prolonged therapy with thiazide diuretics and calcium.

MANAGEMENT: Patients receiving thiazide diuretic therapy should be cautioned against self-treatment with calcium and vitamin D supplements without first talking to their healthcare provider. Serum calcium should be monitored if thiazide diuretics are coadministered with high dosages of calcium and/or vitamin D. Patients should be advised to seek medical attention if they experience signs and symptoms of hypercalcemia such as dizziness, weakness, lethargy, headache, myalgia, anorexia, nausea, vomiting, and seizures.

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MONITOR: The chronic use or abuse of laxatives may potentiate the pharmacologic effects of diuretics. Laxatives can cause significant losses of fluid and electrolytes, including sodium, potassium, magnesium and zinc, and these effects may be additive to those of diuretics.

MANAGEMENT: In general, laxatives should only be used on a short-term, intermittent basis in recommended dosages. During concomitant use with diuretics, patients should be advised to contact their physician if they experience signs and symptoms of fluid and electrolyte depletion such as dizziness, lightheadedness, dry mouth, thirst, fatigue, weakness, lethargy, muscle cramps, decreased urination, postural hypotension, and tachycardia. If maintenance of bowel regularity is required, patients should be advised to exercise and increase fiber in the diet and/or consider the use of bulk-forming laxatives.

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Coadministration with antacids may decrease the oral bioavailability of captopril and other angiotensin converting enzyme (ACE) inhibitors due to delayed gastric emptying and/or elevated gastric pH. In 10 healthy volunteers, 50 mL of an antacid suspension decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of captopril (50 mg single oral dose) by 50% and 42%, respectively, compared to administration after fasting. The relative bioavailability of captopril was 0.66 with antacid, although its hypotensive activity did not seem to be affected. Based on available data, the clinical significance of this interaction appears to be minor. As a precaution, patients may want to consider separating the administration times of ACE inhibitors and antacids or oral medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) by 1 to 2 hours.

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Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

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Coadministration with antacids may decrease the oral bioavailability of captopril and other angiotensin converting enzyme (ACE) inhibitors due to delayed gastric emptying and/or elevated gastric pH. In 10 healthy volunteers, 50 mL of an antacid suspension decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of captopril (50 mg single oral dose) by 50% and 42%, respectively, compared to administration after fasting. The relative bioavailability of captopril was 0.66 with antacid, although its hypotensive activity did not seem to be affected. Based on available data, the clinical significance of this interaction appears to be minor. As a precaution, patients may want to consider separating the administration times of ACE inhibitors and antacids or oral medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) by 1 to 2 hours.

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Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

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