Renal failure: Deferasirox can cause acute renal failure and death, particularly in patient with comorbidities and those who are in the advanced stages of their hematologic disorders. Measure serum creatinine and determine CrCl in duplicate prior to initiation of therapy and monitor renal function at least monthly thereafter. For patients with baseline renal impairment or at increased risk of acute renal failure, monitor creatinine weekly for the first month, then at least monthly thereafter. Consider dose reduction, interruption, or discontinuation based on increases in serum creatinine.
Hepatic failure: Deferasirox can cause hepatic injury, including hepatic failure and death. Measure serum transaminases and bilirubin in all patients prior to initiating treatment, every 2 weeks during the first month, and at least monthly thereafter. Avoid use of deferasirox in patients with severe (Child-Pugh class C) hepatic impairment and reduce the dose in patients with moderate (Child-Pugh class B) hepatic impairment.
Gastrointestinal (GI) hemorrhage: Deferasirox can cause GI hemorrhage, which may be fatal, especially in elderly patients who have advanced hematologic malignancies and/or low platelet counts. Monitor patients and discontinue deferasirox for suspected GI ulceration or hemorrhage.
Renal effects: Deferasirox can cause acute renal failure, fatal in some patients and requiring dialysis in others. Most fatalities occurred in patients with multiple comorbidities and who were in advanced stages of their hematologic disorders.
Measure serum creatinine in duplicate (because of variations in measurements) and determine the CrCl before initiating therapy in all patients to establish a reliable pretreatment baseline. Monitor serum creatinine and/or CrCl at least monthly thereafter or more frequently for increases. Monitor serum creatinine weekly during the first month after initiation or modification of therapy, and at least monthly thereafter. Dose reduction, interruption, or discontinuation based on increases in serum creatinine may be necessary.
Renal tubular damage, including Fanconi syndrome, has been reported in patients treated with deferasirox, most commonly in children and adolescents with beta-thalassemia and serum ferritin levels less than 1,500 mcg/L.
Hepatic effects: Deferasirox can cause hepatic injury, which is fatal in some patients. Hepatic toxicity appears to be more common in patients older than 55 years. Hepatic failure was more common in patients with significant comorbidities, including liver cirrhosis and multiorgan failure. Monitor serum transaminases (ALT and AST) and bilirubin in all patients before the initiation of treatment, every 2 weeks during the first month, and at least monthly thereafter. Consider dosage modifications or interruption of treatment for severe or persistent elevations.
Gastrointestinal (GI) effects: Fatal GI hemorrhages, especially in elderly patients who had advanced hematologic malignancies and/or low platelet counts, have been reported. Nonfatal upper GI irritation, ulceration, and hemorrhage have been reported in patients, including children and adolescents, receiving deferasirox. Monitor signs and symptoms of GI ulceration and hemorrhage during deferasirox therapy, and promptly initiate additional evaluation and treatment if a serious GI adverse reaction is suspected. The risk of GI hemorrhage may be increased when administering deferasirox in combination with drugs that have ulcerogenic or hemorrhagic potential, such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, oral bisphosphonates, or anticoagulants.
Bone marrow suppression: Agranulocytosis, neutropenia, thrombocytopenia, and worsening anemia, including fatal events, have been reported in patients treated with deferasirox. Preexisting hematologic disorders may increase this risk. Monitor blood cell counts in all patients. Interrupt treatment with deferasirox in patients who develop cytopenias until the cause of cytopenia has been determined.
Dermatologic toxicity: May cause skin rash (dose related); mild-to-moderate rashes may resolve without treatment interruption; for severe rash, interrupt and consider restarting at a lower dose with dose escalation and oral steroids. Severe skin reactions, including Stevens-Johnson syndrome and erythema multiforme, have also been reported; discontinue and evaluate if suspected.
Special senses: Auditory disturbances (eg, high-frequency hearing loss, decreased hearing) and ocular disturbances (eg, lens opacities, cataracts, elevations in intraocular pressure, retinal disorders) have been reported. Perform auditory and ophthalmic testing before starting deferasirox and thereafter at regular intervals (every 12 months). If disturbances are noted, monitor more closely and consider dose reduction or interruption of therapy.
Hypersensitivity reactions: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients receiving deferasirox, with the onset of the reaction usually occurring within the first month of treatment. If reactions are severe, discontinue deferasirox and institute appropriate medical intervention.
Effect on ability to drive and use machine: Data is not available.
Use in Children: Safety and effectiveness have not been established in pediatric patients with chronic iron overload due to blood transfusions who are younger than 2 years or pediatric patients with chronic iron overload and nontransfusion-dependent thalassemia who are younger than 10 years.
Use in Elderly: Elderly patients experienced a higher frequency of adverse reactions than younger patients. Closely monitor elderly patients for early signs or symptoms of adverse reactions that may require a dose adjustment. Elderly patients are at an increased risk for deferasirox toxicity because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Deferasirox has been associated with serious and fatal adverse reactions in elderly patients. Monitor elderly patients more frequently for toxicity.