IMPORTANT SAFETY INFORMATION for EXJADE (deferasirox)

EXJADE can cause acute renal failure and death, particularly in patients with comorbidities and those who are in the advanced stages of their hematologic disorders.

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INDICATIONS

Treatment of Chronic Iron Overload Due to Blood Transfusions (Transfusional Iron Overload)

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

  • This indication is based on a reduction of liver iron concentrations (LIC) and serum ferritin (SF) levels. An improvement in survival or disease-related symptoms has not been established

Treatment of Chronic Iron Overload in Non-Transfusion-Dependent Thalassemia Syndromes

EXJADE is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes and with an LIC of at least 5 milligrams of iron per gram of liver dry weight (mg Fe/g dw) and an SF >300 mcg/L.

  • This indication is based on achievement of an LIC <5 mg Fe/g dw. An improvement in survival or disease-related symptoms has not been established

Limitations of Use

  • Controlled clinical trials of EXJADE with myelodysplastic syndromes (MDS) and chronic iron overload due to blood transfusions have not been performed
  • The safety and efficacy of EXJADE when administered with other iron chelation therapy have not been established

 Find out about another treatment option for lowering iron levels

INDICATIONS

Treatment of Chronic Iron Overload Due to Blood Transfusions (Transfusional Iron Overload)

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

  • This indication is based on a reduction of liver iron concentrations (LIC) and serum ferritin (SF) levels. An improvement in survival or disease-related symptoms has not been established

Treatment of Chronic Iron Overload in Non-Transfusion-Dependent Thalassemia Syndromes

EXJADE is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes and with an LIC of at least 5 milligrams of iron per gram of liver dry weight (mg Fe/g dw) and an SF >300 mcg/L.

  • This indication is based on achievement of an LIC <5 mg Fe/g dw. An improvement in survival or disease-related symptoms has not been established

Limitations of Use

  • Controlled clinical trials of EXJADE with myelodysplastic syndromes (MDS) and chronic iron overload due to blood transfusions have not been performed
  • The safety and efficacy of EXJADE when administered with other iron chelation therapy have not been established

IMPORTANT SAFETY INFORMATION for EXJADE® (deferasirox)

WARNING: RENAL FAILURE, HEPATIC FAILURE, AND GASTROINTESTINAL HEMORRHAGE

Renal Failure

  • EXJADE can cause acute renal failure and death, particularly in patients with comorbidities and those who are in the advanced stages of their hematologic disorders
  • Measure serum creatinine and determine creatinine clearance in duplicate prior to initiation of therapy, and monitor renal function at least monthly thereafter. For patients with baseline renal impairment or increased risk of acute renal failure, monitor creatinine weekly for the first month, then at least monthly.  Consider dose reduction, interruption, or discontinuation based on increases in serum creatinine

Hepatic Failure

  • EXJADE 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 EXJADE in patients with severe (Child-Pugh C) hepatic impairment, and reduce the dose in patients with moderate (Child-Pugh B) hepatic impairment

Gastrointestinal Hemorrhage

  • EXJADE can cause gastrointestinal (GI) hemorrhages, which may be fatal, especially in elderly patients who have advanced hematologic malignancies and/or low platelet counts
  • Monitor patients, and discontinue EXJADE for suspected GI ulceration or hemorrhage

CONTRAINDICATIONS

EXJADE is contraindicated in patients with:

  • Serum creatinine >2 times the age-appropriate upper limit of normal or creatinine clearance <40 mL/min;
  • Poor performance status;
  • High-risk MDS;
  • Advanced malignancies;
  • Platelet counts less than 50 x 109/L;
  • Known hypersensitivity to deferasirox or any component of EXJADE

WARNINGS AND PRECAUTIONS

Renal Toxicity, Renal Failure, and Proteinuria

  • EXJADE can cause acute renal failure, fatal in some patients and requiring dialysis in others. Postmarketing experience showed that most fatalities occurred in patients with multiple comorbidities and who were in advanced stages of their hematologic disorders. In the clinical trials, EXJADE‑treated patients experienced dose‑dependent increases in serum creatinine. In patients with transfusional iron overload, these increases occurred at a greater frequency compared to deferoxamine‑treated patients (38% vs 14%, respectively, in Study 1 [patients with β‑thalassemia] and 36% vs 22%, respectively, in Study 3 [patients with sickle cell disease])
  • Measure serum creatinine in duplicate (due to variations in measurements) and determine the creatinine clearance (estimated by the Cockcroft-Gault method) before initiating therapy in all patients in order to establish a reliable pretreatment baseline. Monitor serum creatinine weekly during the first month after initiation or modification of therapy and at least monthly thereafter. Monitor serum creatinine and/or creatinine clearance more frequently if creatinine levels are increasing. Dose reduction, interruption, or discontinuation based on increases in serum creatinine may be necessary
  • EXJADE is contraindicated in patients with creatinine clearance <40 mL/min or serum creatinine >2 times the age-appropriate upper limit of normal
  • Renal tubular damage, including Fanconi Syndrome, has been reported in patients treated with EXJADE, most commonly in children and adolescents with β-thalassemia and serum ferritin (SF) levels <1500 mcg/L
  • 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 (patients with β‑thalassemia). In clinical trials in patients with transfusional iron overload, EXJADE was temporarily withheld until the urine protein/creatinine ratio fell below 0.6 mg/mg. Monthly monitoring for proteinuria is recommended. The mechanism and clinical significance of the proteinuria are uncertain

Hepatic Toxicity and Failure

  • EXJADE can cause hepatic injury, fatal in some patients. In Study 1 (patients with β‑thalassemia), 4 patients (1.3%) discontinued EXJADE because of hepatic toxicity (drug-induced hepatitis in 2 patients and increased serum transaminases in 2 additional patients). Hepatic toxicity appears to be more common in patients >55 years of age. Hepatic failure was more common in patients with significant comorbidities, including liver cirrhosis and multiorgan failure
  • Measure transaminases (AST and ALT) and bilirubin in all patients before the initiation of treatment and every 2 weeks during the first month, and at least monthly thereafter. Consider dose modifications or interruption of treatment for severe or persistent elevations
  • Avoid the use of EXJADE in patients with severe (Child-Pugh C) hepatic impairment. Reduce the starting dose in patients with moderate (Child-Pugh B) hepatic impairment. Patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment may be at higher risk for hepatic toxicity

Gastrointestinal (GI) Ulceration, Hemorrhage, and Perforation

  • GI hemorrhages, including deaths, have been reported, especially in elderly patients who had advanced hematologic malignancies and/or low platelet counts. Nonfatal upper GI irritation, ulceration, and hemorrhage have been reported in patients, including children and adolescents, receiving EXJADE
  • Monitor for signs and symptoms of GI ulceration and hemorrhage during EXJADE therapy, and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected
  • The risk of GI hemorrhage may be increased when administering EXJADE in combination with drugs that have ulcerogenic or hemorrhagic potential, such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, oral bisphosphonates, or anticoagulants. There have been reports of ulcers complicated with GI perforation (including fatal outcome)

Bone Marrow Suppression

  • Neutropenia, agranulocytosis, worsening anemia, and thrombocytopenia, including fatal events, have been reported in patients treated with EXJADE. Pre-existing hematologic disorders may increase this risk
  • Monitor blood counts in all patients. Interrupt treatment with EXJADE in patients who develop cytopenias until the cause of the cytopenia has been determined 
  • EXJADE is contraindicated in patients with platelet counts below 50 x 109/L

Increased Risk of Toxicity in the Elderly

  • EXJADE has been associated with serious and fatal adverse reactions in the postmarketing setting, predominantly in elderly patients. Monitor elderly patients treated with EXJADE more frequently for toxicity

Hypersensitivity

  • EXJADE may cause serious hypersensitivity reactions (such as anaphylaxis and angioedema), with the onset of the reaction usually occurring within the first month of treatment. If reactions are severe, discontinue EXJADE and institute appropriate medical intervention
  • EXJADE is contraindicated in patients with known hypersensitivity to deferasirox products and should not be reintroduced in patients who have experienced previous hypersensitivity reactions on deferasirox products due to the risk of anaphylactic shock

Severe Skin Reactions

  • Severe skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and erythema multiforme, have been reported during EXJADE therapy. The risk of other skin reactions including DRESS (drug reaction with eosinophilia and systemic symptoms) cannot be excluded. If severe skin reactions are suspected, discontinue EXJADE immediately and do not reintroduce EXJADE therapy

Skin Rash

  • Rashes may occur during EXJADE treatment. For rashes of mild to moderate severity, EXJADE may be continued without dose adjustment, since the rash often resolves spontaneously. In severe cases, interrupt treatment with EXJADE. Reintroduction at a lower dose with escalation may be considered after resolution of the rash

Auditory and Ocular Abnormalities

  • Auditory disturbances (high-frequency hearing loss, decreased hearing), and ocular disturbances (lens opacities, cataracts, elevations in intraocular pressure, and retinal disorders) were reported at a frequency of <1% with EXJADE therapy in the clinical studies
  • Perform auditory and ophthalmic testing (including slit lamp examinations and dilated fundoscopy) before starting EXJADE treatment and thereafter at regular intervals (every 12 months). If disturbances are noted, monitor more frequently. Consider dose reduction or interruption

Overchelation

  • For patients with transfusional iron overload, measure SF monthly to assess for possible overchelation of iron. If the SF falls below 500 mcg/L, consider temporarily interrupting therapy with EXJADE since this result may increase EXJADE toxicity
  • For patients with NTDT, measure LIC by liver biopsy or by using an FDA-cleared or approved method for monitoring patients receiving deferasirox therapy every 6 months on treatment. Interrupt EXJADE administration when the LIC is <3 mg Fe/g dw. Measure SF monthly, and if the SF falls below 300 mcg/L, interrupt EXJADE and obtain a confirmatory LIC

ADVERSE REACTIONS

  • For patients with transfusional iron overload, the most common adverse reactions occurring in >5% of EXJADE-treated patients with β‑thalassemia, patients with sickle cell disease, and patients with MDS were abdominal pain, nausea, vomiting, diarrhea, skin rashes, and increases in serum creatinine. Gastrointestinal symptoms, increases in serum creatinine, and skin rash were dose related
  • For patients with NTDT, the most common adverse reactions occurring in >5% of EXJADE-treated patients were nausea, rash, and diarrhea

Please see full Prescribing Information, including Boxed WARNING, for EXJADE (deferasirox).