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Deferasirox (Exjade) - New Boxed Warning about Potentially Fatal Renal, Hepatic, Hematologic, and Allergic Events

February 23, 2010

FDA and Novartis have notified healthcare professionals of potentially fatal renal, hepatic, hematologic, gastrointestinal (GI), and allergic adverse events reported with deferasirox (Exjade) during post-marketing surveillance. Acute renal failure has been reported, including fatalities, primarily in patients with comorbidities and advanced hematologic disease. Hepatic failure, some fatal, has been reported primarily in patients over the age of 55 years, and in patients with comorbidities such as multi-organ failure and liver cirrhosis. Gastrointestinal adverse events reported include ulceration, GI irritation, and GI hemorrhage, with fatal GI hemorrhage reported primarily in elderly patients with hematologic malignancies or low platelet counts. Agranulocytosis, neutropenia, thrombocytopenia, and other potentially fatal cytopenias have occurred, primarily in patients with preexisting hematologic disorders. Reports of allergic reactions include leukocytoclastic vasculitis, urticaria, anaphylaxis, and angioedema. Most severe allergic reactions were reported during the first month of therapy. A boxed warning was added to the product package insert to reflect this information.

Monitor renal function (eg, serum creatinine, creatinine clearance) at baseline and periodically during therapy. In patients with preexisting renal dysfunction or risk factors for renal dysfunction, monitor renal function weekly for 1 month after starting therapy or dosage adjustment, then monthly thereafter. Monitor renal function at least monthly during therapy in all other patients. Consider reducing the dose or temporarily discontinuing therapy if serum creatinine persists above the pretreatment baseline for 2 consecutive measurements (more than 33% above baseline for adults, or above the age-appropriate upper limit of normal for children). If deferasirox is discontinued, therapy may be resumed at a lower dose once serum creatinine returns to the normal range.

Monitor liver function (eg, serum transaminases, bilirubin) at baseline, every 2 weeks for the first month, then monthly thereafter. Reduce the dose or temporarily discontinue deferasirox for severe or persistent increases in liver function tests. Monitor complete blood counts at baseline and periodically during therapy; temporarily discontinue deferasirox if unexplained blood dyscrasias occur.

Monitor patients for signs and symptoms of GI hemorrhage, and evaluate promptly if these occur. Use caution when administering deferasirox in combination with other agents known to cause GI ulceration or hemorrhage. Monitor patients for rashes and other signs of hypersensitivity. Although mild to moderate skin rashes typically resolve without dosage reduction, discontinue deferasirox in patients who develop serious hypersensitivity reactions.

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Updated
February 23, 2010; December 14, 2007; May 23, 2007; University of Utah, Drug Information Service. Copyright 2010, Drug Information Service, University of Utah, Salt Lake City, UT.