Drug Interactions between Aspir-Mox IB and Di-Phen

ADJUST DOSING INTERVAL: Concurrent administration of antacids may decrease the bioavailability of phenytoin. The mechanism of interaction is unknown. In eight healthy volunteers, coadministration of a single 600 mg dose of phenytoin and an antacid containing either aluminum-magnesium hydroxide or calcium carbonate (dose equal to 160 mEq of neutralizing capacity) given one and three hours after meals and at bedtime on the same day resulted in an approximately 25% reduction in the total area under the concentration-time curve (AUC) of phenytoin compared to administration alone. An antacid containing aluminum hydroxide-magnesium trisilicate given in an equivalent dose also reduced the AUC of phenytoin, but the difference was not statistically significant. In another study, aluminum hydroxide-magnesium trisilicate caused a 12% reduction in steady-state serum phenytoin levels in six epileptic patients, but seizure frequency was not affected. There have also been isolated case reports of patients with low serum phenytoin levels or inadequate seizure control attributed to concurrent antacid administration. In a few of the patients, serum phenytoin levels rose two to threefold when antacid administration was delayed by 2 to 3 hours. However, some studies have failed to find a significant interaction with these antacids.

MANAGEMENT: Given the narrow therapeutic index and the large interindividual variability in the pharmacokinetics of phenytoin, patients requiring concomitant antacid therapy should consider separating the times of administration by at least two to three hours if possible. Serum phenytoin levels and seizure activity should be monitored.

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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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ADJUST DOSING INTERVAL: Concurrent administration of antacids may decrease the bioavailability of phenytoin. The mechanism of interaction is unknown. In eight healthy volunteers, coadministration of a single 600 mg dose of phenytoin and an antacid containing either aluminum-magnesium hydroxide or calcium carbonate (dose equal to 160 mEq of neutralizing capacity) given one and three hours after meals and at bedtime on the same day resulted in an approximately 25% reduction in the total area under the concentration-time curve (AUC) of phenytoin compared to administration alone. An antacid containing aluminum hydroxide-magnesium trisilicate given in an equivalent dose also reduced the AUC of phenytoin, but the difference was not statistically significant. In another study, aluminum hydroxide-magnesium trisilicate caused a 12% reduction in steady-state serum phenytoin levels in six epileptic patients, but seizure frequency was not affected. There have also been isolated case reports of patients with low serum phenytoin levels or inadequate seizure control attributed to concurrent antacid administration. In a few of the patients, serum phenytoin levels rose two to threefold when antacid administration was delayed by 2 to 3 hours. However, some studies have failed to find a significant interaction with these antacids.

MANAGEMENT: Given the narrow therapeutic index and the large interindividual variability in the pharmacokinetics of phenytoin, patients requiring concomitant antacid therapy should consider separating the times of administration by at least two to three hours if possible. Serum phenytoin levels and seizure activity should be monitored.

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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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ADJUST DOSING INTERVAL: Concurrent administration of antacids may decrease the bioavailability of phenytoin. The mechanism of interaction is unknown. In eight healthy volunteers, coadministration of a single 600 mg dose of phenytoin and an antacid containing either aluminum-magnesium hydroxide or calcium carbonate (dose equal to 160 mEq of neutralizing capacity) given one and three hours after meals and at bedtime on the same day resulted in an approximately 25% reduction in the total area under the concentration-time curve (AUC) of phenytoin compared to administration alone. An antacid containing aluminum hydroxide-magnesium trisilicate given in an equivalent dose also reduced the AUC of phenytoin, but the difference was not statistically significant. In another study, aluminum hydroxide-magnesium trisilicate caused a 12% reduction in steady-state serum phenytoin levels in six epileptic patients, but seizure frequency was not affected. There have also been isolated case reports of patients with low serum phenytoin levels or inadequate seizure control attributed to concurrent antacid administration. In a few of the patients, serum phenytoin levels rose two to threefold when antacid administration was delayed by 2 to 3 hours. However, some studies have failed to find a significant interaction with these antacids.

MANAGEMENT: Given the narrow therapeutic index and the large interindividual variability in the pharmacokinetics of phenytoin, patients requiring concomitant antacid therapy should consider separating the times of administration by at least two to three hours if possible. Serum phenytoin levels and seizure activity should be monitored.

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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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In vitro studies suggest that salicylates may displace phenytoin from plasma protein-binding sites. The potential for phenytoin toxicity exists. The clinical significance is unknown. One case of phenytoin toxicity has been reported in a patient taking aspirin. However, clinical studies in healthy subjects and epileptic patients (taking phenytoin and 1500 mg aspirin/day) have not reported significant pharmacokinetic changes, adverse effects, or loss of seizure control.

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