Drug Interactions between etidronate 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: Theoretical concerns exist regarding the potential for increased risk and severity of gastrointestinal toxicity during coadministration of oral bisphosphonates and nonsteroidal anti-inflammatory drugs (NSAIDs) due to additive or synergistic irritant effects on the gastrointestinal mucosa. Because NSAIDs reduce the rate of ulcer healing in the stomach and duodenum, it is also possible that NSAIDs may delay healing and exaggerate the mucosal injury caused by oral bisphosphonates. In a blinded, randomized, crossover study consisting of 26 healthy volunteers, investigators using endoscopic techniques reported a significantly higher incidence of gastric ulcers following combined treatment with alendronate 10 mg once a day and naproxen 500 mg twice a day for 14 days than after treatment with either alendronate or naproxen alone (38% vs. 8% and 12%, respectively). In contrast, a 3-year controlled clinical study found no significant difference in the incidence of upper gastrointestinal adverse events between alendronate 5 or 10 mg/day and placebo given to more than 2000 subjects, most of whom received concomitant NSAIDs. Likewise, the incidence of upper gastrointestinal adverse events was similar for risedronate (24.5%) and placebo (24.8%) among patients who were regular users (>= 3 days/week) of aspirin or NSAIDs in phase 3 osteoporosis studies, which enrolled a total of over 5700 patients. Aspirin use was reported by 31% of patients and NSAID use by 48% of patients, 24% and 21% of whom were regular users, respectively.

MONITOR: Theoretical concerns exist regarding the potential for increased risk and severity of renal impairment during coadministration of bisphosphonates with high dosages or chronic use of NSAIDs due to additive or synergistic nephrotoxic effects on the kidney. The use of bisphosphonates has been associated with nephrotoxicity manifested as deterioration of renal function and renal failure. Cases have primarily involved intravenous formulations of the drugs such as pamidronic acid and zoledronic acid, especially when they are administered too rapidly. The risk of hypocalcemia may also be increased, as drug-induced renal tubular damage can lead to renal loss of calcium and other electrolytes such as magnesium. Bisphosphonates alone often cause mild, asymptomatic hypocalcemia via inhibitive effects on bone resorption and possibly chelation of blood calcium. Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with renal toxicities including elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure.

MANAGEMENT: Caution is advised if bisphosphonates are prescribed in combination with NSAIDs. Patients receiving oral bisphosphonates should be closely monitored for the development of gastrointestinal toxicity and advised to immediately report potential signs and symptoms such as severe abdominal pain, nausea, vomiting, diarrhea, loss of appetite, dizziness, lightheadedness, and/or black, tarry stools. Patients receiving intravenous formulations of bisphosphonates should have renal function and serum electrolytes closely monitored. Serum creatinine should be assessed prior to each treatment, and treatment should be withheld in the presence of renal deterioration. In patients treated for bone metastases, treatment should not be resumed until renal function returns to baseline.

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ADJUST DOSING INTERVAL: Products containing aluminum, calcium, magnesium and other polyvalent cations such as antacids or vitamin with mineral supplements are likely to interfere with the gastrointestinal absorption of oral bisphosphonates. For example, the bioavailability of tiludronate has been shown to decrease 80% during simultaneous administration with calcium, and 60% when aluminum- or magnesium-containing antacids were administered one hour before tiludronate.

MANAGEMENT: Antacids or other oral medications containing aluminum, calcium, magnesium and other polyvalent cations should be administered at least 2 hours before or 2 hours after the bisphosphonate dose.

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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: Products containing aluminum, calcium, magnesium and other polyvalent cations such as antacids or vitamin with mineral supplements are likely to interfere with the gastrointestinal absorption of oral bisphosphonates. For example, the bioavailability of tiludronate has been shown to decrease 80% during simultaneous administration with calcium, and 60% when aluminum- or magnesium-containing antacids were administered one hour before tiludronate.

MANAGEMENT: Antacids or other oral medications containing aluminum, calcium, magnesium and other polyvalent cations should be administered at least 2 hours before or 2 hours after the bisphosphonate dose.

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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: Products containing aluminum, calcium, magnesium and other polyvalent cations such as antacids or vitamin with mineral supplements are likely to interfere with the gastrointestinal absorption of oral bisphosphonates. For example, the bioavailability of tiludronate has been shown to decrease 80% during simultaneous administration with calcium, and 60% when aluminum- or magnesium-containing antacids were administered one hour before tiludronate.

MANAGEMENT: Antacids or other oral medications containing aluminum, calcium, magnesium and other polyvalent cations should be administered at least 2 hours before or 2 hours after the bisphosphonate dose.

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