Medication Labeling Change Alert

May 22, 2007

ISSUE:	Revised labeling of Exjade® (deferasorix) due to post-marketing reports of acute renal failure and cytopenias including some with fatal outcome
MEDICATIONS:	Exjade® (deferasorix) tablets for oral suspension, Novartis

The following was posted on FDA Med Watch alert website dated May 22, 2007:

"Novartis and FDA notified healthcare professionals of changes to the WARNINGS and ADVERSE REACTIONS sections of the product labeling for Exjade, a drug used to treat chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. Cases of acute renal failure, some with a fatal outcome, have been reported following the post marketing use of Exjade. Most of the fatalities occurred in patients with multiple co-morbidities and who were in advanced stages of their hematological disorders. Additionally, there were post marketing reports of cytopenias, including agranulocytosis, neutropenia and thrombocytopenia in patients treated with Exjade where some of the patients died. The relationship of these episodes to treatment with Exjade is uncertain. Most of these patients had preexisting hematologic disorders that are frequently associated with bone marrow failure. Further, cases of leukocytoclastic vasculitis, urticaria, and hypersensitivity reactions (including anaphylaxis and angioedema) were reported. Healthcare professionals should monitor serum creatinine in patients who are at increased risk of complications, having preexisting renal conditions, are elderly, have co-morbid conditions, or are receiving medicinal products that depress renal function. Blood counts should also be monitored regularly and treatment should be interrupted in patients who develop unexplained cytopenia.”

An excerpt of Novartis’ "Dear Health Care Provider" letter dated May 14, 2007 is provided below:

“Novartis is writing to summarize the December 2006 changes made to the WARNINGS and ADVERSE REACTIONS sections of the Exjade® (deferasirox) Tablets.

Renal- Cases of acute renal failure, some with a fatal outcome, have been reported following the postmarketing use of Exjade® (deferasirox). Particular attention should be given to monitoring serum creatinine in patients who: are at increased risk of complications, have preexisting renal conditions, are elderly, have co-morbid conditions, or are receiving medicinal products that depress renal function. Serum creatinine should be assessed in duplicate before initiating therapy to establish a reliable pre-treatment baseline, due to variations in measurements. Serum creatinine should be monitored monthly thereafter. Patients with additional renal risk factors should be monitored weekly during the first month after initiation or modification of therapy, and monitored monthly thereafter.

Cytopenias- There have been postmarketing reports of cytopenias, including agranulocytosis, neutropenia and thrombocytopenia, in patients treated with Exjade. Some of these patients died. The relationship of these episodes to treatment with Exjade is uncertain. Most of these patients had preexisting hematologic disorders that are frequently associated with bone marrow failure. In line with the standard clinical management of such hematological disorders, blood counts should be monitored regularly. Interruption of treatment with Exjade should be considered in patients who develop unexplained cytopenia. Reintroduction of therapy with Exjade may be considered, once the cause of the cytopenia has been elucidated.

Postmarketing Experience- There have been reports of cytopenias, including agranulocytosis, neutropenia and thrombocytopenia, in patients treated with Exjade. Although most of these patients had preexisting hematologic disorders that are frequently associated with bone marrow failure, a contributory role for Exjade cannot be excluded. Cases of acute renal failure have been reported in the context of severe complications relating to the underlying disease.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of Exjade® to Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover NJ 07936 or by phone (888-NOW NOVARTIS or 888 669 6682) or the internet at http://www.novartis.com".