Drug Interactions between Magnaprin and valproic acid

MONITOR: Salicylates, particularly aspirin, may displace valproate from protein binding sites and inhibit its clearance. Four-fold increases in the free fraction of valproate have been reported in children. Increased therapeutic and toxic effects may be expected to occur. This interaction is more likely with large or prolonged doses of salicylates.

MANAGEMENT: Small single doses of salicylates are unlikely to cause significant effects. However, patients who take large doses of salicylates or over a prolonged period of time should be closely monitored for clinical and laboratory evidence of valproate toxicity and hepatotoxicity. Free fraction of valproate may be particularly helpful in detecting this interaction. Patients should be advised to notify their physician if they experience possible symptoms of toxicity (e.g., malaise, weakness, lethargy, drowsiness, nausea, vomiting, or abdominal pain).

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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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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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Limited data suggest that concurrent administration of antacids may increase the bioavailability of valproic acid. The mechanism of interaction is unknown. In seven healthy volunteers, coadministration of a single 500 mg dose of valproic acid one hour after breakfast and an antacid containing aluminum-magnesium hydroxide (dose equal to 160 mEq of neutralizing capacity) one and three hours after meals and at bedtime on the same day resulted in a mean 12% increase (range 3% to 28%) in the total area under the concentration-time curve (AUC) of valproic acid compared to administration alone. These changes are unlikely to be of clinical importance, and no special precautions appear to be necessary. Equivalent doses of antacids containing either aluminum hydroxide-magnesium trisilicate or calcium carbonate also increased the AUC of valproic acid, but the differences were not statistically significant.

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Limited data suggest that concurrent administration of antacids may increase the bioavailability of valproic acid. The mechanism of interaction is unknown. In seven healthy volunteers, coadministration of a single 500 mg dose of valproic acid one hour after breakfast and an antacid containing aluminum-magnesium hydroxide (dose equal to 160 mEq of neutralizing capacity) one and three hours after meals and at bedtime on the same day resulted in a mean 12% increase (range 3% to 28%) in the total area under the concentration-time curve (AUC) of valproic acid compared to administration alone. These changes are unlikely to be of clinical importance, and no special precautions appear to be necessary. Equivalent doses of antacids containing either aluminum hydroxide-magnesium trisilicate or calcium carbonate also increased the AUC of valproic acid, but the differences were not statistically significant.

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Limited data suggest that concurrent administration of antacids may increase the bioavailability of valproic acid. The mechanism of interaction is unknown. In seven healthy volunteers, coadministration of a single 500 mg dose of valproic acid one hour after breakfast and an antacid containing aluminum-magnesium hydroxide (dose equal to 160 mEq of neutralizing capacity) one and three hours after meals and at bedtime on the same day resulted in a mean 12% increase (range 3% to 28%) in the total area under the concentration-time curve (AUC) of valproic acid compared to administration alone. These changes are unlikely to be of clinical importance, and no special precautions appear to be necessary. Equivalent doses of antacids containing either aluminum hydroxide-magnesium trisilicate or calcium carbonate also increased the AUC of valproic acid, but the differences were not statistically significant.

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