EXJADE is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older.

Further studies are being performed to determine the long-term benefits and risks of EXJADE.

Important Safety Information

EXJADE is contraindicated in patients with hypersensitivity to deferasirox or to any other component of EXJADE.

Cases of acute renal failure, some with a fatal outcome, have been reported following the postmarketing use of EXJADE. Most of the fatalities occurred in patients with multiple comorbidities and who were in advanced stages of their hematologic disorders. Particular attention should be given to monitoring serum creatinine in patients who are at increased risk of complications, have pre-existing renal conditions, are elderly, have comorbid conditions, or are receiving medicinal products that depress renal function.

Serum creatinine should be assessed in duplicate before initiating therapy to establish a reliable pretreatment baseline, due to variations in measurements. Serum creatinine should be monitored monthly thereafter. Patients with additional renal risk factors (those who are at increased risk of complications, have pre-existing renal conditions, are elderly, have comorbid conditions, or are receiving medicinal products that depress renal function) should have serum creatinine monitored weekly during the first month after initiation or modification of therapy, and monthly thereafter. Nonprogressive increases in serum creatinine have been noted in 38% of EXJADE-treated patients, compared to 14% of deferoxamine-treated patients, and appear to be dose related. These increases were within the normal range in 94% of patients. EXJADE dosages were adjusted when serum creatinine elevations were detected during the study.

Dose reduction, interruption, or discontinuation should be considered for elevations in serum creatinine. If there is a progressive increase in serum creatinine beyond the age-appropriate upper limit of normal, EXJADE should be interrupted. Once the creatinine has returned to within the normal range, therapy with EXJADE may be reinitiated at a lower dose followed by gradual dose escalation, if the clinical benefit is expected to outweigh potential risks.

Intermittent proteinuria (urine protein/creatinine ratio >0.6 mg/mg) occurred in 18.6% of EXJADE-treated patients, compared to 7.2% of deferoxamine-treated patients in Study 1, and monthly monitoring is recommended.

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 pre-existing hematologic disorders that are frequently associated with bone marrow failure. In line with standard clinical management, blood counts should be monitored regularly and dose interruption considered in patients who develop unexplained cytopenia. Reintroduction of therapy with EXJADE may be considered once the cause of the cytopenia has been elucidated.

There have been postmarketing reports of hepatic failure, some with a fatal outcome, in patients treated with EXJADE. Most of these events occurred in patients greater than 55 years of age. Most reports of hepatic failure involved patients with significant comorbidities, including liver cirrhosis and multi-organ failure. Liver function tests should be monitored monthly, and if there is an unexplained, persistent, or progressive increase in serum transaminase levels, treatment with EXJADE should be modified or interrupted. In Study 1, seventeen (5.7%) patients treated with EXJADE developed elevations in SGPT/ALT levels >5 times the upper limit of normal at 2 consecutive visits versus five (1.7%) patients treated with deferoxamine.

Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving EXJADE, with the onset of the reaction occurring in the majority of cases within the first month of treatment. If reactions are severe, EXJADE should be discontinued and appropriate medical intervention instituted.

Auditory (high-frequency hearing loss, decreased hearing) and ocular (lens opacities, cataracts, elevations in intraocular pressure, and retinal disorders) disturbances have been reported with EXJADE therapy in less than 1% of patients in clinical trials. Auditory and ophthalmic testing (including slit lamp examinations and dilated fundoscopy) are recommended before the start of EXJADE treatment and thereafter at regular intervals (every 12 months). If disturbances are noted, dose reduction or interruption should be considered.

Skin rashes may occur during treatment with EXJADE. For rashes of mild to moderate severity, EXJADE may be continued without dose adjustment, since the rash often resolves spontaneously. For more severe rashes where interruption of treatment may be necessary, EXJADE may be reintroduced at a lower dose and gradually escalated after resolution of the rash. Reintroduction of EXJADE at a lower dose with escalation may be considered in combination with a short period of oral steroid administration.

The most frequently occurring adverse events with EXJADE included diarrhea, vomiting, nausea, headache, abdominal pain, pyrexia, cough, and increases in serum creatinine. Maintenance of adequate hydration for patients experiencing diarrhea or vomiting is recommended. Gastrointestinal symptoms, increases in serum creatinine, and skin rash were dose related. These commonly reported adverse events were predominantly mild to moderate in severity with serious adverse events reported in 9.1% of patients in the EXJADE arm and 8.6% of patients in the deferoxamine arm.

Please see the full prescribing information.