Drug Interactions between Magnaprin and selpercatinib

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of selpercatinib and reduce its concentrations in plasma. According to the product labeling, the aqueous solubility of selpercatinib is pH-dependent, from freely soluble at low pH to slightly soluble at neutral pH. When selpercatinib was administered under fasted conditions with multiple daily doses of the proton pump inhibitor omeprazole, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 88% and 69%, respectively, compared to selpercatinib administered alone while fasting. The interaction may also occur with other acid reducing or neutralizing agents and may result in diminished anti-tumor activity of selpercatinib.

MANAGEMENT: Concomitant use of selpercatinib with locally-acting antacids or other agents with acid neutralizing or reducing effects should generally be avoided. If coadministration is required, the manufacturer recommends taking selpercatinib 2 hours before or 2 hours after the antacid.

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GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of selpercatinib and reduce its concentrations in plasma. According to the product labeling, the aqueous solubility of selpercatinib is pH-dependent, from freely soluble at low pH to slightly soluble at neutral pH. When selpercatinib was administered under fasted conditions with multiple daily doses of the proton pump inhibitor omeprazole, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 88% and 69%, respectively, compared to selpercatinib administered alone while fasting. The interaction may also occur with other acid reducing or neutralizing agents and may result in diminished anti-tumor activity of selpercatinib.

MANAGEMENT: Concomitant use of selpercatinib with locally-acting antacids or other agents with acid neutralizing or reducing effects should generally be avoided. If coadministration is required, the manufacturer recommends taking selpercatinib 2 hours before or 2 hours after the antacid.

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GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of selpercatinib and reduce its concentrations in plasma. According to the product labeling, the aqueous solubility of selpercatinib is pH-dependent, from freely soluble at low pH to slightly soluble at neutral pH. When selpercatinib was administered under fasted conditions with multiple daily doses of the proton pump inhibitor omeprazole, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 88% and 69%, respectively, compared to selpercatinib administered alone while fasting. The interaction may also occur with other acid reducing or neutralizing agents and may result in diminished anti-tumor activity of selpercatinib.

MANAGEMENT: Concomitant use of selpercatinib with locally-acting antacids or other agents with acid neutralizing or reducing effects should generally be avoided. If coadministration is required, the manufacturer recommends taking selpercatinib 2 hours before or 2 hours after the antacid.

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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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