Drug Interactions between Magnaprin and tacrolimus

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.

Switch to consumer interaction data

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.

Switch to consumer interaction data

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.

Switch to consumer interaction data

MONITOR: Coadministration with aluminum-magnesium hydroxide may increase tacrolimus blood concentrations in vivo. The mechanism of interaction is unknown. In a single-dose study, administration of tacrolimus with aluminum-magnesium hydroxide in healthy volunteers resulted in a 10% and 21% increase in tacrolimus peak concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration without aluminum-magnesium hydroxide. This finding contradicts the results from an in vitro study, which showed that tacrolimus incubated in 100 mL simulated gastric fluid with the equivalent of 500 mg of various antacids resulted in loss of tacrolimus, due presumably to a pH-mediated degradation of tacrolimus. Specifically, Mylanta caused a 14% loss of tacrolimus in 24 hours, magnesium oxide caused a 98% loss in 12 hours, and calcium carbonate caused a 30% loss in 24 hours. In contrast, aluminum hydroxide gel caused an immediate 35% loss of tacrolimus (within 2 minutes) and no further loss for 24 hours, suggesting adsorption of tacrolimus.

MANAGEMENT: Given the narrow therapeutic index and the large interindividual variability in the pharmacokinetics of tacrolimus, caution is advised if the drug is used in combination with aluminum and/or magnesium hydroxide. Pharmacologic response and tacrolimus blood levels should be monitored more closely whenever aluminum/magnesium hydroxide is added to or discontinued from therapy, and the immunosuppressant dosage adjusted as necessary. Patients should be advised to contact their doctor if they experience potential signs and symptoms of tacrolimus toxicity such as fever, infection, diarrhea, tremor, headache, fatigue, lethargy, and changes in motor function, mental status, or sensory function.

Switch to consumer interaction data

MONITOR: Coadministration with aluminum-magnesium hydroxide may increase tacrolimus blood concentrations in vivo. The mechanism of interaction is unknown. In a single-dose study, administration of tacrolimus with aluminum-magnesium hydroxide in healthy volunteers resulted in a 10% and 21% increase in tacrolimus peak concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration without aluminum-magnesium hydroxide. This finding contradicts the results from an in vitro study, which showed that tacrolimus incubated in 100 mL simulated gastric fluid with the equivalent of 500 mg of various antacids resulted in loss of tacrolimus, due presumably to a pH-mediated degradation of tacrolimus. Specifically, Mylanta caused a 14% loss of tacrolimus in 24 hours, magnesium oxide caused a 98% loss in 12 hours, and calcium carbonate caused a 30% loss in 24 hours. In contrast, aluminum hydroxide gel caused an immediate 35% loss of tacrolimus (within 2 minutes) and no further loss for 24 hours, suggesting adsorption of tacrolimus.

MANAGEMENT: Given the narrow therapeutic index and the large interindividual variability in the pharmacokinetics of tacrolimus, caution is advised if the drug is used in combination with aluminum and/or magnesium hydroxide. Pharmacologic response and tacrolimus blood levels should be monitored more closely whenever aluminum/magnesium hydroxide is added to or discontinued from therapy, and the immunosuppressant dosage adjusted as necessary. Patients should be advised to contact their doctor if they experience potential signs and symptoms of tacrolimus toxicity such as fever, infection, diarrhea, tremor, headache, fatigue, lethargy, and changes in motor function, mental status, or sensory function.

Switch to consumer interaction data

In vitro data suggest that the presence of antacids may reduce the bioavailability of tacrolimus. An in vitro study showed that tacrolimus incubated in 100 mL simulated gastric fluid with the equivalent of 500 mg of various antacids resulted in loss of tacrolimus, due presumably to a pH-mediated degradation of tacrolimus. Specifically, aluminum-magnesium hydroxide caused a 14% loss of tacrolimus in 24 hours, magnesium oxide caused a 98% loss in 12 hours, and calcium carbonate caused a 30% loss in 24 hours. In contrast, aluminum hydroxide gel caused an immediate 35% loss of tacrolimus (within 2 minutes) and no further loss for 24 hours, suggesting adsorption of tacrolimus. Whether these effects occur in vivo, and to what extent, are unknown. Sodium bicarbonate has been reported to cause widely variable trough plasma levels and reduced blood concentrations of tacrolimus when given close to the time of administration of tacrolimus. No other details were available in the report. However, in a single-dose study, administration of tacrolimus with aluminum-magnesium hydroxide in healthy volunteers resulted in a 10% and 21% increase (not decrease) in tacrolimus peak concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration without aluminum-magnesium hydroxide.

Switch to consumer interaction data