Drug Interactions between erlotinib and Magnaprin

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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MONITOR: Coadministration of erlotinib with anti-angiogenic agents, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or taxane-based chemotherapy may increase the risk of gastrointestinal (GI) perforation. Erlotinib treatment has been associated with an increased risk of developing gastrointestinal (GI) perforation, including fatal cases. Patients with a prior history of peptic ulceration or diverticular disease may also have an increased risk. In three lung cancer studies with erlotinib monotherapy and a pancreatic cancer study with erlotinib plus gemcitabine, the incidence of gastrointestinal perforation in patients treated with erlotinib was 0.2% and 0.4%, respectively, compared to 0.1% and 0% in the control arms. Cases of GI bleeding have also been reported with concomitant administration of NSAIDs.

MANAGEMENT: Caution is recommended when using erlotinib in patients with a history of peptic ulceration or diverticular disease and in patients receiving concomitant treatment with drugs associated with an increased risk of GI perforation such as anti-angiogenic agents, corticosteroids, NSAIDs, and taxane-based chemotherapy. Patients should be advised to contact their healthcare provider if they experience signs and symptoms of GI perforation such as severe abdominal pain, fever, chills, nausea, or vomiting. The manufacturer recommends that erlotinib should be permanently discontinued in patients who develop gastrointestinal perforation.

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ADJUST DOSING INTERVAL: Concurrent administration of antacids or other agents with acid-neutralizing effects may decrease the oral bioavailability of erlotinib and reduce its concentrations in plasma. The solubility of erlotinib decreases when the pH is over 5, resulting in reduced absorption. Coadministration with the proton pump inhibitor omeprazole or the H2-receptor antagonist ranitidine has been found to significantly reduce the plasma concentrations of erlotinib. When coadministered with omeprazole, erlotinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 61% and 46%, respectively. When coadministered with ranitidine 300 mg, erlotinib Cmax and AUC decreased by 54% and 33%, respectively. The interaction has not been studied with antacids.

MANAGEMENT: If an antacid or other agent with acid-neutralizing effects is required during erlotinib therapy, it should be administered at least 4 hours before or 2 hours after the daily dose of erlotinib.

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ADJUST DOSING INTERVAL: Concurrent administration of antacids or other agents with acid-neutralizing effects may decrease the oral bioavailability of erlotinib and reduce its concentrations in plasma. The solubility of erlotinib decreases when the pH is over 5, resulting in reduced absorption. Coadministration with the proton pump inhibitor omeprazole or the H2-receptor antagonist ranitidine has been found to significantly reduce the plasma concentrations of erlotinib. When coadministered with omeprazole, erlotinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 61% and 46%, respectively. When coadministered with ranitidine 300 mg, erlotinib Cmax and AUC decreased by 54% and 33%, respectively. The interaction has not been studied with antacids.

MANAGEMENT: If an antacid or other agent with acid-neutralizing effects is required during erlotinib therapy, it should be administered at least 4 hours before or 2 hours after the daily dose of erlotinib.

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ADJUST DOSING INTERVAL: Concurrent administration of antacids or other agents with acid-neutralizing effects may decrease the oral bioavailability of erlotinib and reduce its concentrations in plasma. The solubility of erlotinib decreases when the pH is over 5, resulting in reduced absorption. Coadministration with the proton pump inhibitor omeprazole or the H2-receptor antagonist ranitidine has been found to significantly reduce the plasma concentrations of erlotinib. When coadministered with omeprazole, erlotinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 61% and 46%, respectively. When coadministered with ranitidine 300 mg, erlotinib Cmax and AUC decreased by 54% and 33%, respectively. The interaction has not been studied with antacids.

MANAGEMENT: If an antacid or other agent with acid-neutralizing effects is required during erlotinib therapy, it should be administered at least 4 hours before or 2 hours after the daily dose of erlotinib.

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