Drug Interaction Report

MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

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MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

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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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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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ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

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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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GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

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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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H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

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