For Healthcare Professionals Outside the US

EXJADE® 

Important note: Before prescribing, consult full prescribing information.

Presentation: Dispersible tablets containing 125 mg, 250 mg or 500 mg of deferasirox. Film-coated tablets containing 90 mg, 180 mg or 360 mg of deferasirox. Granules in sachet containing 90 mg, 180 mg or 360 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 pediatric 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 adult and pediatric patients with other anemias aged 2 years and older; in adult and pediatric 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 nontransfusion-dependent thalassemia syndromes aged 10 years and older.

Dosage: Transfusional iron overload

Dispersible tablets ◆ 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. 

Film-coated tablets ◆ Recommended initial daily dose is 14 mg/kg body weight; consider 21 mg/kg for patients receiving >14 ml/kg/month of packed red blood cells        (>4 units/month), and for whom the objective is reduction of iron overload; consider 7 mg/kg for patients receiving <7 ml/kg/month of packed red blood cells                        (<2 units/month), and for whom the objective is maintenance of the body iron level; for patients already well-managed on treatment with deferoxamine, consider a starting dose of EXJADE  that is numerically one third that of the deferoxamine dose. For patients who are currently on chelation therapy with the dispersible tablet and switching to the film-coated tablet, the dose should be 30% lower, rounded to the nearest whole tablet. ◆ The film-coated tablets should be swallowed whole with some water. For patients who are unable to swallow whole tablets, the tablets may be crushed and administered by sprinkling the full dose on soft food like yogurt or apple sauce (apple puree). The dose should be immediately and completely consumed, and not stored for future use. EXJADE should be taken once a day, preferably at the same time each day, and may be taken on an empty stomach or with a light meal. ◆ 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 3.5 to 7 mg/kg. ◆ Maximum daily dose is 28 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 3.5 to 7 mg/kg to maintain serum ferritin levels within the target range. ◆ Interrupt treatment if serum ferritin falls consistently below 500 micrograms/l.

Granules in sachet ◆ Recommended initial daily dose is 14 mg/kg body weight; consider 21 mg/kg for patients receiving >14 ml/kg/month of packed red blood cells        (>4 units/month), and for whom the objective is reduction of iron overload; consider 7 mg/kg for patients receiving <7 ml/kg/month of packed red blood cells                        (< 2 units/month), and for whom the objective is maintenance of the body iron level; for patients already well-managed on treatment with deferoxamine, consider a starting dose of EXJADE  that is numerically one third that of the deferoxamine dose. For patients who are currently on chelation therapy with the dispersible tablet and switching to the granules, the dose should be 30% lower, rounded to the nearest whole sachet. ◆ The granules should be administered by sprinkling the full dose onto soft food like yogurt or apple sauce (apple puree). The dose should be immediately and completely consumed, and not stored for future use. The soft food containing the granules should be taken once a day, preferably at the same time each day, and may be taken on an empty stomach or with a light meal. ◆ 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 3.5 to 7 mg/kg. ◆ Maximum daily dose is 28 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 3.5 to 7 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

Dispersible tablets ◆ Recommended initial daily dose is 10 mg/kg body weight. 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. In patients with no LIC assessment, 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.

Film-coated tablets ◆ Recommended initial daily dose is 7 mg/kg body weight. 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. In patients with no LIC assessment, caution should be taken during chelation therapy to minimize the risk of over-chelation. For patients who are currently on chelation therapy with the dispersible tablet and switching to the film-coated tablet, the dose should be 30% lower, rounded to the nearest whole tablet. ◆ Monthly monitoring of serum ferritin ◆ Dose adjustment should be considered every 3 to 6 months in steps of 3.5 to 7 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 14 mg/kg body weight.◆ In pediatric patients the dosing should not exceed 7 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.

Granules in sachet ◆ Recommended initial daily dose is 7 mg/kg body weight. 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. In patients with no LIC assessment, caution should be taken during chelation therapy to minimize the risk of over-chelation. For patients who are currently on chelation therapy with the dispersible tablet and switching to the granules, the dose should be 30% lower, rounded to the nearest whole sachet. ◆ Monthly monitoring of serum ferritin ◆ Dose adjustment should be considered every 3 to 6 months in steps of 3.5 to 7 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 14 mg/kg body weight.◆ In pediatric patients the dosing should not exceed 7 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 ◆ In moderate hepatic impairment (Child-Pugh B) dose should not exceed 50% of the normal dose. 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 prior to therapy, weekly in the first month after initiation or modification of therapy (including switch of formulation), 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 with cases of metabolic acidosis, mainly in children and adolescents with beta-thalassemia. Severe forms of renal tubulopathy (such as Fanconi syndrome) and renal failure associated with changes in consciousness in the context of hyperammonaemic encephalopathy have been reported, mainly in children. 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. Severe forms of hepatic failure associated with changes in consciousness in the context of hyperammonaemic encephalopathy may occur, particularly in children.  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 • 109/l and in patients taking anticoagulants or other drugs with known ulcerogenic potential. Acute pancreatitis has been reported, particularly in children and adolescents. ◆ Interrupt treatment if severe skin rash develops. ◆ Consider reintroduction at a lower dose followed by dose escalation.           ◆ Severe cutaneous adverse reactions (SCARs), e.g cases of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and DRESS (drug reaction with eosinophilia and systemic symptoms) have been reported. Patients should be advised of the signs and symptoms of SCARs and be closely monitored. If any SCAR is suspected EXJADE should be discontinued immediately and not reintroduced ◆ 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. If used, additional or alternative non-hormonal contraception is recommended. ◆ 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, cholestyramine) 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. ◆ Consider dose adjustment of busulfan when used concomitantly, as EXJADE may increase exposure of busulfan.

 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, cataract, maculopathy, deafness, laryngeal pain, gastrointestinal hemorrhage, gastric ulcer, duodenal ulcer, gastritis, hepatitis, cholelithiasis, pigmentation disorder, renal tubular disorder (acquired Fanconi syndrome), glycosuria, pyrexia, edema, fatigue. ◆ Rare: Esophagitis, optic neuritis, DRESS (drug reaction with eosinophilia and systemic symptoms). ◆ Not Known (cannot be estimated from data): Stevens-Johnson syndrome, pancytopenia, thrombocytopenia, neutropenia, aggravated anemia, hypersensitivity reactions (including anaphylactic reactions and angioedema), metabolic acidosis, gastrointestinal perforation, acute pancreatitis, hepatic failure, hypersensitivity vasculitis, urticaria, erythema multiforme, alopecia, toxic epidermal necrolysis (TEN), acute renal failure, tubulointerstitial nephritis, nephrolithiasis, renal tubular necrosis. ◆ Refer to the SmPC for a full list of adverse reactions.

 

Legal Category: country specific

Packs: country specific information

This medical product is subject to additional monitoring.

This will allow quick identification of new safety information.

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

BSS July 2018 based on SmPC July 2018