Deferasirox

Decreased hearing and high-frequency hearing loss have been reported (rare) with use; perform auditory testing prior to initiation and regularly (every 12 months) during use; if abnormalities develop, monitor more closely and consider dose reduction or treatment interruption.

Cytopenias (including agranulocytosis, neutropenia, thrombocytopenia, and worsening anemia) have been reported (some fatal); risk may be increased in patients with preexisting hematologic disorders; monitor blood counts regularly. Interrupt treatment in patients who develop cytopenias; may reinitiate once cause of cytopenia has been determined; use contraindicated if platelet count 3.

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 (SJS), toxic epidermal necrolysis and erythema multiforme, have also been reported; the risk of other skin reactions including drug reaction with eosinophilia and systemic symptoms (DRESS) cannot be excluded. If severe skin reactions are suspected, discontinue immediately and evaluate; do not reintroduce therapy.

GI hemorrhages (including fatalities) may occur; observed more frequently in elderly patients with advanced hematologic malignancies and/or low platelet counts; discontinue treatment for suspected GI hemorrhage or ulceration. Nonfatal upper GI irritation, hemorrhage, and ulceration (sometimes complicated with GI perforation, including fatalities) have been reported. Use caution with concurrent medications that may increase risk of adverse GI effects (eg, NSAIDs, corticosteroids, anticoagulants, oral bisphosphonates). Monitor patients closely for signs/symptoms of GI ulceration/bleeding.

Hepatic injury and failure (including fatalities) may occur. Monitor transaminases and bilirubin at baseline, every 2 weeks for 1 month, then at least monthly thereafter. Hepatitis and elevated transaminases have also been reported. Hepatotoxicity is more common in patients >55 years and in patients with significant comorbidities (eg, cirrhosis, multiorgan failure). Reduce dose or temporarily interrupt treatment for severe or persistent increases in transaminases/bilirubin.

Hypersensitivity reactions, including severe reactions (anaphylaxis and angioedema) have been reported; onset is usually within the first month of treatment. Discontinue if reaction is severe and do not reintroduce patients with previous hypersensitivity reactions due to risk of anaphylactic shock.

Lens opacities, cataracts, intraocular pressure elevation, and retinal disorders have been reported (rare) with use; perform ophthalmic testing prior to initiation and regularly (every 12 months) during use; if abnormalities develop, monitor more closely and consider dose reduction or treatment interruption.

Acute renal failure (including fatalities and cases requiring dialysis) may occur; observed more frequently in patients with comorbid conditions and patients in advanced stages of hematologic disorders. Obtain serum creatinine and calculate CrCl in duplicate prior to initiation of therapy and monitor at least monthly thereafter. For patients with baseline renal impairment or at increased risk of acute renal failure, monitor creatinine weekly during the first month then at least monthly thereafter. Consider dose reduction, interruption, or discontinuation based on increases in serum creatinine. Monitor serum creatinine and/or CrCl more frequently if creatinine levels are increasing. May cause proteinuria; monitor monthly although the clinical significance of proteinuria is unknown. Renal tubular damage, including Fanconi syndrome, has also been reported, primarily in pediatric/adolescent patients with beta-thalassemia and serum ferritin levels Disease-related concerns:

Avoid use in patients with severe (Child-Pugh class C) hepatic impairment; dose reduction is required in patients with moderate (Child-Pugh class B) hepatic impairment. Monitor patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) impairment closely for efficacy and for adverse reactions requiring dosage reduction.

In patients with baseline renal impairment, monitor creatinine weekly during the first month then at least monthly thereafter. Consider dose reduction, interruption, or discontinuation based on increases in serum creatinine. Reductions in initial dose are recommended for patients with CrCl 40 to 60 mL/minute; use is contraindicated in patients with a CrCl 2 times age-appropriate ULN. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Use with caution due to the higher incidence of toxicity (eg, hepatotoxicity) and fatal events during use; monitor elderly patients closely. Dosage form specific issues:

Some formulations may contain lactose. Other warnings/precautions:

For transfusion-related iron overload, treatment should be initiated with evidence of chronic iron overload (ie, transfusion of ≥100 mL/kg of packed RBCs [eg, ≥20 units for a 40 kg individual] and serum ferritin consistently >1,000 mcg/L). For non-transfusion-dependent iron overload, initiate with liver iron concentration ≥5 mg Fe/g dry liver weight, and serum ferritin >300 mcg/L. Prior to use, consider risk versus anticipated benefit with respect to individual patient's life expectancy, prognosis, and comorbidities. An improvement in survival or disease-related symptoms due to the therapy has not been established in clinical trials. Postmarketing experience indicates serious reactions, including fatalities, have occurred with deferasirox use, particularly when used in older patients with comorbidities or advanced disease.

Deferasirox has a low affinity for binding with zinc and copper, may cause variable decreases in the serum concentration of these trace minerals.

Overchelation of iron may increase development of toxicity; monitor sodium ferritin; consider temporary interruption of treatment in transfusional iron overload when serum ferritin