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EXJADE®

Important note: Before prescribing, consult full prescribing information.

Presentation: Dispersible tablets containing 125 mg, 250 mg or 500 mg of deferasirox.

Indications: For the treatment of chronic iron overload due to frequent blood transfusions (≥7 ml/kg/month of packed red blood cells) in patients with beta-thalassemia major aged 6 years and older.

  • Also indicated for the treatment of chronic iron overload due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in the following patient groups: in patients with beta-thalassemia major with iron overload due to frequent blood transfusions (≥7 ml/kg/month of packed red blood cells) aged 2 to 5 years; in patients with other anemias aged 2 years and older; in patients with beta-thalassemia major with iron overload due to infrequent blood transfusions (<7 ml/kg/month of packed red blood cells) aged 2 years and older.
  • For the treatment of chronic iron overload requiring chelation therapy when deferoxamine therapy is contraindicated or inadequate in patients with non–transfusion-dependent thalassemia syndromes aged 10 years and older.

Dosage: Transfusional iron overload

  • Recommended initial daily dose is 20 mg/kg body weight; consider 30 mg/kg for frequently transfused patients receiving >14 ml/kg/month of packed red blood cells (approximately >4 units/month) who require reduction of iron overload; consider 10 mg/kg for infrequently transfused patients receiving <7 ml/kg/month of packed red blood cells (approximately <2 units/month) who do not require reduction of body iron level; for patients already well-managed on treatment with deferoxamine, consider a starting dose of EXJADE that is numerically half that of the deferoxamine dose.
  • EXJADE must be taken once daily on an empty stomach at least 30 minutes before food.
  • Tablets to be dispersed in water or apple or orange juice (100-200ml).

Monthly monitoring of serum ferritin to assess patient's response to therapy

  • Dose to be adjusted if necessary every 3 to 6 months based on serum ferritin trends. Dose adjustments should be made in steps of 5 to 10 mg/kg. In patients not adequately controlled with doses of 30 mg/kg, doses of up to 40 mg/kg may be considered.

Maximum daily dose is 40 mg/kg body weight.

  • In patients whose serum ferritin level has reached the target (usually between 500 and 1,000 micrograms/l), consider dose reductions in steps of 5 to 10 mg/kg to maintain serum ferritin levels within the target range.
  • Interrupt treatment if serum ferritin falls consistently below 500 micrograms/l.

Dosage: Non–transfusion-dependent thalassemia syndromes and iron overload

  • Recommended initial daily dose is 10 mg/kg body weight. Chelation therapy should only be initiated when there is evidence of iron overload: liver iron concentration (LIC) ≥5 mg Fe/g dry weight (dw) or serum ferritin consistently >800 micrograms/l. LIC is the preferred method of iron overload determination and should be used whenever available. Caution should be taken during chelation therapy to minimize the risk of over-chelation.

Monthly monitoring of serum ferritin

  • Dose adjustment should be considered every 3 to 6 months in steps of 5 to 10 mg/kg if the patient's LIC is ≥7 mg Fe/g dw, or serum ferritin is consistently >2,000 micrograms/l, and not showing a downward trend, and the patient is tolerating the drug well. Once a satisfactory body iron level has been achieved (LIC <3 mg Fe/g dw or serum ferritin <300 micrograms/l), treatment should be stopped. There are no data available on the retreatment of patients who reaccumulate iron after having achieved a satisfactory body iron level and therefore retreatment cannot be recommended.

Maximum daily dose is 20 mg/kg body weight.

  • In pediatric patients the dosing should not exceed 10 mg/kg; closer monitoring of LIC and serum ferritin is essential to avoid overchelation: in addition to monthly serum ferritin assessments, LIC should be monitored every 3 months when serum ferritin is ≤800 micrograms/l.
  • Dosage: Special population
  • 50% starting dose reduction in moderate hepatic impairment (Child-Pugh B). Should not be used in severe hepatic impairment (Child-Pugh C).

Contraindications:

  • Hypersensitivity to deferasirox or to any of the excipients.
  • Combination with other iron chelator therapies.
  • Estimated creatinine clearance <60 ml/min.

Warnings/Precautions:

  • Renal Function: Assess serum creatinine in duplicate before initiating therapy; monitor serum creatinine, creatinine clearance and/or plasma cystatin C levels weekly in the first month after initiation or modification of therapy, and monthly thereafter. Dose reduction or interruption may be required in some cases where rises in serum creatinine occur. Postmarketing cases of renal failure (some requiring dialysis) have been reported. There have been reports of renal tubulopathy, mainly in children and adolescents with beta-thalassemia. Tests for proteinuria should be performed monthly. Refer the patient to a renal specialist and consider further specialized investigations (such as renal biopsy) if serum creatinine remains significantly elevated and another marker of renal function is also persistently abnormal.
  • Hepatic Function: Monitor serum transaminases, bilirubin and alkaline phosphatase before the initiation of treatment, every 2 weeks during the first month and monthly thereafter. Interrupt treatment if persistent and progressive unattributable increase in serum transaminase levels occur. Postmarketing cases of hepatic failure (sometimes fatal) have been reported. Not recommended in patients with severe hepatic impairment (Child-Pugh C).
  • Caution in elderly patients due to a higher frequency of adverse reactions. Not recommended in patients with a short life expectancy (e.g. high-risk myelodysplastic syndromes) especially when co-morbidities could increase the risk of adverse events.
  • Gastrointestinal irritation may occur. Upper gastrointestinal ulceration and hemorrhage, including ulcers complicated with digestive perforation, have been reported in patients, including children and adolescents. There have been reports of fatal gastrointestinal hemorrhages, especially in elderly patients who had hematologic malignancies and/or low platelet counts. Caution in patients with platelet counts <50 x 109/l and in patients taking anticoagulants or other drugs with known ulcerogenic potential.
  • Cases of Stevens-Johnson syndrome (SJS) have been reported during the post-marketing period. The risk of other more severe skin reactions (TEN [toxic epidermal necrolysis], DRESS [drug reaction with eosinophilia and systemic symptoms] cannot be excluded. If SJS or any other severe skin reaction is suspected EXJADE should be discontinued.
  • Interrupt treatment if severe skin rash develops.
  • Consider reintroduction at a lower dose followed by dose escalation.
  • Discontinue if severe hypersensitivity reaction occurs.
  • Annual ophthalmological/audiological testing.
  • Annual monitoring for body weight, height and sexual development in pediatric patients.
  • Interruption of treatment should be considered in patients who develop unexplained cytopenia.
  • Cardiac function should be monitored in patients with severe iron overload during long-term EXJADE treatment.
  • Should not be used during pregnancy unless clearly necessary.
  • Not recommended when breastfeeding.
  • Product contains lactose.

Interactions:

  • Must not be combined with other iron chelator therapies.
  • Should not be taken with aluminum-containing antacids.
  • Caution when combined with drugs metabolized through CYP3A4 (e.g. cyclosporine, simvastatin, hormonal contraceptive agents, bepridil, ergotamine).
  • Concomitant use with potent UGT inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital, ritonavir, cholesteramine) may result in a decrease in EXJADE efficacy.
  • Careful monitoring of glucose levels should be performed when repaglinide (a CYP2C8 substrate) and EXJADE are used concomitantly. EXJADE may also increase levels of other CYP2C8 substrates like paclitaxel.
  • Consider monitoring of theophylline concentration and possible theophylline dose reduction. Interaction with other CYP1A2 substrates may be possible.
  • Caution when combined with drugs with ulcerogenic potential (e.g. NSAIDs, corticosteroids, oral bisphosphonates) or with anticoagulants.

Adverse reactions:

  • Very common: Blood creatinine increased.
  • Common: Headache, diarrhea, constipation, vomiting, nausea, abdominal pain, abdominal distension, dyspepsia, transaminases increased, rash, pruritus, proteinuria.
  • Uncommon: anxiety, sleep disorder, dizziness, early cataract, maculopathy, hearing loss, pharyngolaryngeal pain, gastrointestinal hemorrhage, gastric ulcer, duodenal ulcer, gastritis, hepatitis, cholelithiasis, pigmentation disorder, renal tubulopathy (acquired Fanconi's syndrome), glycosuria, pyrexia, edema, fatigue.
  • Rare: Esophagitis, optic neuritis.
  • Not Known (cannot be estimated from data): Stevens-Johnson syndrome, Pancytopenia, thrombocytopenia, neutropenia, aggravated anemia, hypersensitivity reactions (including anaphylaxis and angioedema), metabolic acidosis, gastrointestinal perforation, hepatic failure, leukocytoclastic vasculitis, urticaria, erythema multiforme, alopecia, acute renal failure, tubulointerstitial nephritis, nephrolithiasis, renal tubular necrosis.
  • Refer to the SmPC for a full list of adverse reactions.

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This medical product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.