Drug Interactions between Magnaprin and penicillamine

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: Oral administration of aluminum, copper, iron, zinc, magnesium, and possibly other minerals such as calcium may decrease the gastrointestinal absorption of penicillamine, and vice versa. The proposed mechanism involves chelation of penicillamine to polyvalent cations, which leads to formation of a nonabsorbable complex. In a study of six healthy volunteers, administration of penicillamine (500 mg) following a single dose of ferrous sulfate (300 mg) or antacid (Maalox Plus 30 mL) reduced the mean peak plasma concentration of penicillamine by 65% and 34%, respectively, compared to administration in the fasting state. In addition to chelation, some investigators suggest that antacids may also reduce penicillamine bioavailability by increasing gastric pH, which favors the oxidation of penicillamine to its poorly absorbed disulfide form. These changes could result in diminished therapeutic effects of penicillamine.

MANAGEMENT: Mineral supplements or other products containing polyvalent cations (e.g., antacids or preparations containing antacids such as didanosine buffered tablets or pediatric oral solution) should be administered at least two hours before or two hours after the penicillamine dose. In addition, pharmacologic response to penicillamine should be monitored more closely whenever these products are added to or withdrawn from therapy, and the penicillamine dosage adjusted as necessary. When penicillamine is coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering penicillamine at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium.

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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: Oral administration of aluminum, copper, iron, zinc, magnesium, and possibly other minerals such as calcium may decrease the gastrointestinal absorption of penicillamine, and vice versa. The proposed mechanism involves chelation of penicillamine to polyvalent cations, which leads to formation of a nonabsorbable complex. In a study of six healthy volunteers, administration of penicillamine (500 mg) following a single dose of ferrous sulfate (300 mg) or antacid (Maalox Plus 30 mL) reduced the mean peak plasma concentration of penicillamine by 65% and 34%, respectively, compared to administration in the fasting state. In addition to chelation, some investigators suggest that antacids may also reduce penicillamine bioavailability by increasing gastric pH, which favors the oxidation of penicillamine to its poorly absorbed disulfide form. These changes could result in diminished therapeutic effects of penicillamine.

MANAGEMENT: Mineral supplements or other products containing polyvalent cations (e.g., antacids or preparations containing antacids such as didanosine buffered tablets or pediatric oral solution) should be administered at least two hours before or two hours after the penicillamine dose. In addition, pharmacologic response to penicillamine should be monitored more closely whenever these products are added to or withdrawn from therapy, and the penicillamine dosage adjusted as necessary. When penicillamine is coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering penicillamine at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium.

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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: Oral administration of aluminum, copper, iron, zinc, magnesium, and possibly other minerals such as calcium may decrease the gastrointestinal absorption of penicillamine, and vice versa. The proposed mechanism involves chelation of penicillamine to polyvalent cations, which leads to formation of a nonabsorbable complex. In a study of six healthy volunteers, administration of penicillamine (500 mg) following a single dose of ferrous sulfate (300 mg) or antacid (Maalox Plus 30 mL) reduced the mean peak plasma concentration of penicillamine by 65% and 34%, respectively, compared to administration in the fasting state. In addition to chelation, some investigators suggest that antacids may also reduce penicillamine bioavailability by increasing gastric pH, which favors the oxidation of penicillamine to its poorly absorbed disulfide form. These changes could result in diminished therapeutic effects of penicillamine.

MANAGEMENT: Mineral supplements or other products containing polyvalent cations (e.g., antacids or preparations containing antacids such as didanosine buffered tablets or pediatric oral solution) should be administered at least two hours before or two hours after the penicillamine dose. In addition, pharmacologic response to penicillamine should be monitored more closely whenever these products are added to or withdrawn from therapy, and the penicillamine dosage adjusted as necessary. When penicillamine is coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering penicillamine at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium.

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