Drug Interactions between Aspirin Buffered and deferasirox

MONITOR CLOSELY: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal bleeding associated with the use of deferasirox. Fatal gastrointestinal hemorrhages have been reported during deferasirox therapy, especially in elderly patients with advanced hematologic malignancies and/or low platelet counts. Non-fatal upper gastrointestinal irritation, ulceration, and hemorrhage have also been reported, including in children and adolescents.

MONITOR CLOSELY: Theoretical concerns exist regarding the potential for increased risk of renal impairment during coadministration of deferasirox with other nephrotoxic agents, including NSAIDs when used chronically or in high dosages. The use of deferasirox has been associated with postmarketing reports of acute renal failure, in some cases resulting in dialysis or even fatality. Most fatalities occurred in patients with multiple comorbidities and who were in advanced stages of their haematological disorders. In clinical studies, patients treated with deferasirox experienced dose-dependent increases in serum creatinine. These increases occurred at a greater frequency than in deferoxamine-treated patients (38% vs. 14%, respectively, in one study and 36% vs. 22%, respectively, in another study). Most of the creatinine elevations remained within the normal range. There have also been reports of renal tubulopathy in patients treated with deferasirox. The majority of these patients were children and adolescents with beta-thalassemia and serum ferritin levels below 1500 mcg/L. Deferasirox has not been studied for use in patients with baseline serum creatinine above the upper limit of normal.

MANAGEMENT: Caution is advised if deferasirox is used in combination with NSAIDs. Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, bloating, dizziness, lightheadedness, vomiting blood, anorexia, or black, tarry stools. Serum creatinine and/or creatinine clearance should be closely monitored (e.g., prior to initiation of deferasirox therapy, then weekly during the first month after initiation or modification of therapy and monthly thereafter), especially in the elderly and patients with preexisting renal impairment, comorbid conditions, dehydration, or severe infections. Dosage reduction, interruption, or discontinuation should be considered in the presence of creatinine elevations. A progressive increase in serum creatinine beyond the age-appropriate upper limit of normal may warrant an interruption of therapy. Once the creatinine has returned to within the normal range, therapy may be reinitiated at a lower dose followed by a gradual dose escalation according to the product labeling, provided the clinical benefit is expected to outweigh potential risks. In clinical studies, the daily dosage of deferasirox was reduced by 10 mg/kg for increases of serum creatinine on two consecutive measures (i.e., >33% in patients older than 15 years of age, or >33% and greater than the age-appropriate upper limit of normal in patients younger than 15 years of age). Care should be taken to maintain adequate hydration in patients who develop diarrhea or vomiting.

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.

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.

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.

GENERALLY AVOID: Although deferasirox has a lower affinity for aluminum than for iron, it can theoretically bind aluminum in the gastrointestinal tract.

MANAGEMENT: Deferasirox should not be taken with aluminum-containing preparations.