DEFERASIROX (TYPE J)

). 4 Geriatrics). The pharmacokinetics of deferasirox have not been studied in elderly patients. In clinical trials, elderly patients experienced a higher frequency of adverse reactions than younger patients and should be monitored closely for adverse reactions that may require a dose adjustment.

2 CONTRAINDICATIONS DEFERASIROX (TYPE J) is contraindicated in: • patients with estimated creatinine clearance <60 mL/min or serum creatinine >2 times the age-appropriate upper limit of normal (ULN). • high risk myelodysplastic syndrome (MDS) patients, any other MDS patient with a life expectancy < 1 year and patients with other hematological and non-hematological malignancies who are not expected to benefit from chelation therapy due to the rapid progression of their disease.

• patients with platelet counts < 50 x 109/L. • patients with hypersensitivity to the active substance, deferasirox, or to any of the excipients. For a complete listing of excipients, see the

). Auditory testing is recommended before the start of DEFERASIROX (TYPE J) treatment and thereafter at regular intervals. 5 mg/kg/day deferasirox film-coated tablets when serum ferritin was less than 1,000 mcg/L (patients received high doses despite body iron burden being in the target range or consistently below the target range which is not recommended; see 4 DOSAGE AND ADMINISTRATION).

Gastrointestinal Gastrointestinal irritation may occur during DEFERASIROX (TYPE J) treatment. Upper gastrointestinal (GI) ulceration and haemorrhage and upper and lower GI perforations have been reported uncommonly in patients, including children and adolescents, receiving deferasirox.

There have been rare reports of fatal GI haemorrhages and perforations. Fatal haemorrhages have been reported more frequently in elderly patients who had advanced hematologic malignancies and/or low platelet counts. Multiple ulcers have been observed in some patients and there have been reports of ulcers complicated with gastrointestinal perforation (see 8 ADVERSE REACTIONS).

Physicians and patients should remain alert for signs and symptoms of GI ulceration, perforation and haemorrhage during DEFERASIROX (TYPE J) therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected.

Caution should be exercised in patients who are taking DEFERASIROX (TYPE J) in combination with drugs that have known ulcerogenic potential, such as NSAIDs, corticosteroids, or oral bisphosphonates, and in patients receiving anticoagulants (see

3 Pharmacokinetics). DEFERASIROX (TYPE J) requires a different dosing regimen and method of administration compared to deferasirox dispersible tablets. To avoid dosing errors, it is important that prescriptions of deferasirox specify both the type of formulation (dispersible tablet or film- coated tablet) and the prescribed dose in mg/kg/day.

This medicine is also available as a tablet that is meant to be dissolved in liquid before drinking. The doses of these two formulations are not the same. Be sure you are taking the right type of deferasirox. Check with your doctor, nurse or pharmacist if you are not sure.

1 Dosing Considerations • Deferasirox film-coated tablets and deferasirox dispersible tablets for oral suspension are different formulations of deferasirox. Deferasirox film-coated tablets require a different dosing regimen and method of administration compared to deferasirox dispersible tablets.

If converting from deferasirox dispersible tablets for oral suspension to deferasirox film-coated tablets, see the Dosing Considerations section below. • To avoid dosing errors, it is important that prescriptions of deferasirox specify both the type of formulation (dispersible tablets for oral suspension or film-coated tablets) and the prescribed dose in mg/kg/day.

2 Recommended Dose and Dosage Adjustment A. Transfusional iron overload The goals of iron chelation therapy are to remove the amount of iron administered in PrDEFERASIROX (TYPE J) (Deferasirox Tablets) Page 6 of 51 transfusions and as required, to reduce the existing iron burden.

The decision to remove accumulated iron should be individualized based on anticipated clinical benefit and risks of chelation therapy. It is recommended that therapy with DEFERASIROX (TYPE J) (deferasirox) be started when a patient has evidence of chronic iron overload, such as the transfusion of approximately 100 mL/kg of packed red blood cells (approximately 20 units for a 40 kg patient) and a serum ferritin consistently >1000 mcg/L.

DEFERASIROX (TYPE J) is contraindicated in: • patients with estimated creatinine clearance <60 mL/min or serum creatinine >2 times the age-appropriate upper limit of normal (ULN). • high risk myelodysplastic syndrome (MDS) patients, any other MDS patient with a life expectancy < 1 year and patients with other hematological and non-hematological malignancies who are not expected to benefit from chelation therapy due to the rapid progression of their disease.

• patients with platelet counts < 50 x 109/L. • patients with hypersensitivity to the active substance, deferasirox, or to any of the excipients. For a complete listing of excipients, see the 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

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