Frequently asked questions about EXJADE®

EXJADE is a chelation therapy promoting the excretion of iron, primarily through the feces.

To learn more about EXJADE, choose one of the following links.

This information is based on the EU Summary of Product Characteristics that is not country-specific. Please consult your local prescribing information and/or contact your local Novartis representative. You can also consult www.novartisoncology.com.

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General Questions

EXJADE is a tridentate ligand that binds iron with high affinity, forming a 2:1 complex that is excreted in bile and eliminated primarily via the feces.

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EXJADE is administered orally, once daily on an empty stomach at least 30 minutes before food, preferably at the same time each day. The tablets are dispersed by stirring in a glass of water or orange or apple juice (100 to 200 mL) until a fine suspension is obtained. After the suspension has been swallowed, any residue must be resuspended in a small volume of water or juice and swallowed. The tablets must not be chewed or swallowed whole. Learn more about dosing.

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EXJADE is available in 3 tablet sizes: 125 mg, 250 mg, and 500 mg although not all sizes may be available in all countries. Learn more about dosing.

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Deferasirox and its metabolites are primarily excreted in the feces (84% of the dose). Renal excretion of deferasirox and its metabolites is minimal (8% of the dose). The mean elimination half-life (t½) ranged from 8 to 16 hours.

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Check your local prescribing information, which can be found via www.novartisoncology.com, or ask your local sales representative.

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Taking EXJADE

EXJADE is indicated 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.

EXJADE is 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 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
  • in patients with other anemias aged 2 years and older

EXJADE is also indicated 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.

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In patients with chronic iron overload due to blood transfusions, it is recommended that therapy with EXJADE be started after the transfusion of approximately 20 units (about 100 ml/kg) of packed red blood cells, or when there is evidence from clinical monitoring that chronic iron overload is present (eg, serum ferritin >1000 µg/l).

In non–transfusion-dependent thalassemia syndromes, 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 µg/l). LIC is the preferred method of iron overload determination and should be used wherever available. Caution should be taken during chelation therapy to minimise the risk of over-chelation in all patients.Learn more about EXJADE.

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In patients with chronic iron overload due to blood transfusions, the recommended initial daily dose of EXJADE is 20 mg/kg body weight. An initial daily dose of 30 mg/kg may be considered for patients receiving more than 14 ml/kg/month of packed red blood cells (corresponding to approximately >4 units/month for an adult), and for whom the objective is reduction of iron toxicity.

An initial daily dose of 10 mg/kg may be considered for patients receiving less than 7 ml/kg/month of packed red blood cells (corresponding to approximately <2 units/month for an adult), and for whom the objective is maintenance of the body iron level.

For non–transfusion-dependent thalassemia, the 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.

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In patients with chronic iron overload due to blood transfusions already well managed on treatment with deferoxamine, a starting dose of EXJADE that is numerically half that of the deferoxamine dose could be considered (eg, a patient receiving 40 mg/kg/day of deferoxamine for 5 days per week [or equivalent] could be transferred to a starting daily dose of 20 mg/kg of EXJADE).

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In patients with chronic iron overload due to blood transfusions, it is recommended that serum ferritin be monitored every month, and that the dose of EXJADE be adjusted if necessary every 3 to 6 months based on the trends in serum ferritin. Dose adjustments may be made in steps of 5 to 10 mg/kg, and are to be tailored to the individual patient's response and therapeutic goals (maintenance or reduction of iron burden).

In non–transfusion-dependent thalassemia syndromes, it is recommended that serum ferritin be monitored every month. After every 3 to 6 months of treatment, a dose increase in increments of 5 to 10 mg/kg should be considered if the patient's LIC is ≥7 mg Fe/g dw, or if serum ferritin is consistently >2,000 µg/l and not showing a downward trend, and the patient is tolerating the medicinal product well. Doses above 20 mg/kg are not recommended because there is no experience with doses above this level in patients with non–transfusion-dependent thalassemia syndromes.

In patients in whom LIC was not assessed and serum ferritin is ≤2,000 µg/l, dosing should not exceed 10 mg/kg.

For patients in whom the dose was increased to >10 mg/kg, dose reduction to 10 mg/kg or less is recommended when LIC is <7 mg Fe/g dw or serum ferritin is ≤2,000 µg/l.

Treatment cessation

Once a satisfactory body iron level has been achieved (LIC <3 mg Fe/g dw or serum ferritin <300 µg/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.

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EXJADE must be taken orally, once daily on an empty stomach at least 30 minutes before food, preferably at the same time each day. The tablets are dispersed by stirring in a glass of water or orange or apple juice (100 to 200 ml) until a fine suspension is obtained. After the suspension has been swallowed, any residue must be resuspended in a small volume of water or juice and swallowed. The tablets must not be chewed or swallowed whole.

Dispersion in carbonated drinks or milk is not recommended due to foaming and slow dispersion, respectively.Learn more about dosing.

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The dosing recommendations for elderly and pediatric patients are the same as for adults. Changes in weight of pediatric patients over time must be taken into account when calculating the dose.

The dosing recommendations for pediatric patients aged 2 to 17 years with transfusional iron overload are the same as for adult patients. Changes in weight of pediatric patients over time must be taken into account when calculating the dose. In children with transfusional iron overload aged between 2 and 5 years, exposure is lower than in adults. This age group may therefore require higher doses than are necessary in adults. However, the initial dose should be the same as in adults, followed by individual titration.

In pediatric patients with non–transfusion-dependent thalassemia syndromes, dosing should not exceed 10 mg/kg. In these patients, closer monitoring of LIC and serum ferritin is essential to avoid overchelation: in addition to monthly serum ferritin assessments, LIC should be monitored every three months when serum ferritin is ≤800 µg/l.

The safety and efficacy of EXJADE in children from birth to 23 months of age have not been established. No data are available.

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It is recommended that serum creatinine be assessed in duplicate before initiating therapy. Serum creatinine, creatinine clearance (estimated with the Cockcroft-Gault or MDRD formula in adults and with the Schwartz formula in children) and/or plasma cystatin C levels should be monitored weekly in the first month after initiation or modification of therapy with EXJADE, and monthly thereafter.

Tests for proteinuria should be performed monthly.

It is recommended that serum transaminases, bilirubin, and alkaline phosphatase be checked before the initiation of treatment, every 2 weeks during the first month and monthly thereafter.

Auditory and ophthalmic testing (including fundoscopy) is recommended before the start of treatment and at regular intervals thereafter (every 12 months).

As a general precautionary measure in the management of pediatric patients with transfusional iron overload, body weight, height and sexual development should be monitored at regular intervals (every 12 months).

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EXJADE is contraindicated with the combination of other iron chelator therapies as the safety of such combinations has not been established.

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Special considerations

EXJADE has not been studied in patients with renal impairment and is contraindicated in patients with creatinine clearance <60 mL/min.

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EXJADE has been studied only in patients with baseline serum creatinine within the age-appropriate normal range.

It is recommended that serum creatinine be assessed in duplicate before initiating therapy. Serum creatinine, creatinine clearance (estimated with the Cockcroft-Gault or MDRD formula in adults and with the Schwartz formula in children) and/or plasma cystatin C levels should be monitored weekly in the first month after initiation or modification of therapy with EXJADE, and monthly thereafter. Patients with pre-existing renal conditions and patients who are receiving medicinal products that depress renal function may be more at risk of complications. Care should be taken to maintain adequate hydration in patients who develop diarrhea or vomiting.

There have been post-marketing reports of metabolic acidosis occurring during treatment with EXJADE. The majority of these patients had renal impairment, renal tubulopathy (Fanconi's syndrome) or diarrhoea, or conditions where acid-base imbalance is a known complication. Acid-base balance should be monitored as clinically indicated in these populations. Interruption of EXJADE therapy should be considered in patients who develop metabolic acidosis.

For adult patients, the daily dose may be reduced by 10 mg/kg if a rise in serum creatinine by >33% above the average of the pre-treatment measurements and estimated creatinine clearance decreases below the lower limit of the normal range (<90 mL/min) are seen at two consecutive visits, and cannot be attributed to other causes. For pediatric patients, the dose may be reduced by 10 mg/kg if estimated creatinine clearance decreases below the lower limit of the normal range (<90 mL/min) and/or serum creatinine levels rise above the age-appropriate upper limit of normal at two consecutive visits.

After a dose reduction, for adult and pediatric patients, treatment should be interrupted if a rise in serum creatinine >33% above the average of the pre-treatment measurements is observed and/or the calculated creatinine clearance falls below the lower limit of the normal range. Treatment may be reinitiated depending on the individual clinical circumstances.

Renal tubulopathy has been mainly reported in children and adolescents with β-thalassemia treated with EXJADE. Tests for proteinuria should be performed monthly. As needed, additional markers of renal tubular function (eg, glycosuria in non-diabetics and low levels of serum potassium, phosphate, magnesium or urate, phosphaturia, aminoaciduria) may also be monitored. Dose reduction or interruption may be considered if there are abnormalities in levels of tubular markers and/or if clinically indicated.

If, despite dose reduction and interruption, the serum creatinine remains significantly elevated and there is also persistent abnormality in another marker of renal function (eg, proteinuria, Fanconi's Syndrome), the patient should be referred to a renal specialist, and further specialized investigations(such as renal biopsy) may be considered.

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EXJADE is not recommended in patients with severe hepatic impairment (Child-Pugh Class C). In patients with moderate hepatic impairment (Child-Pugh Class B), the dose should be considerably reduced followed by progressive increase up to a limit of 50%, and must be used with caution in such patients. Hepatic function in all patients should be monitored before treatment, every 2 weeks during the first month and then every month. If there is a persistent and progressive increase in serum transaminase levels that cannot be attributed to other causes, EXJADE should be interrupted. Once the cause of the liver function test abnormalities has been clarified or after return to normal levels, cautious re-initiation of treatment at a lower dose followed by gradual dose escalation may be considered.

The pharmacokinetics of EXJADE were not influenced by liver transminase levels up to 5 times the upper limit of the normal range.

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Hypersensitivity to the active substance or to any of the excipients.

Combination with other iron chelator therapies as the safety of such combinations has not been established.
Patients with estimated creatinine clearance <60 mL/min.

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Each tablet contains 136 mg lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, or severe lactase deficiency should not take this medicine.

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The concomitant administration of EXJADE and aluminum-containing antacid preparations has not been formally studied. Although EXJADE has a lower affinity for aluminum than for iron, EXJADE tablets must not be taken with aluminum-containing antacid preparations.

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No clinical data on exposed pregnancies are available for deferasirox. Studies in animals have shown some reproductive toxicity at maternally toxic doses. The potential risk for humans is unknown. As a precaution, it is recommended that EXJADE not be used during pregnancy unless clearly necessary.

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Side effects

No studies on the effects of EXJADE on the ability to drive and use machines have been performed. Patients experiencing the uncommon adverse reaction of dizziness should exercise caution when driving or operating machinery.

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The most frequent reactions reported during chronic treatment with EXJADE in adult and pediatric patients include gastrointestinal disturbances in about 26% of patients (mainly nausea, vomiting, diarrhea, or abdominal pain) and skin rash in about 7% of patients. Diarrhea is reported more commonly in pediatric patients aged 2 to 5 years and in the elderly. These reactions are dose-dependent, mostly mild to moderate, generally transient, and mostly resolve even if treatment is continued.

Click here to review the full list of adverse reactions

During clinical trials, increases in serum creatinine of >33% on ≥2 consecutive occasions, sometimes above the upper limit of the normal range, occurred in about 36% of patients. These were dose-dependent. About two-thirds of the patients showing serum creatinine increase returned below the 33% level without dose adjustment. In the remaining third the serum creatinine increase did not always respond to a dose reduction or a dose interruption. Indeed, in some cases, only a stabilization of the serum creatinine values has been observed after dose reduction.

Gallstones and related biliary disorders were reported in about 2% of patients. Elevations of liver transaminases were reported as an adverse drug reaction in 2% of patients. Elevations of transaminases greater than 10 times the upper limit of the normal range, suggestive of hepatitis, were uncommon (0.3%). During postmarketing experience, hepatic failure, sometimes fatal, has been reported with EXJADE, especially in patients with pre-existing liver cirrhosis. There have been post-marketing reports of metabolic acidosis. The majority of these patients had renal impairment, renal tubulopathy (Fanconi's syndrome) or diarrhoea, or conditions where acid-base imbalance is a known complication. Serious acute pancreatitis may potentially occur as a complication of gallstones (and related biliary disorders). As with other iron chelator treatment, high-frequency hearing loss and lenticular opacities (early cataracts) have been uncommonly observed in patients treated with EXJADE. See your local prescribing information for further details.

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Cases of overdose (2 to 3 times the prescribed dose for several weeks) have been reported. In one case, this resulted in subclinical hepatitis, which resolved without long-term consequences after a dose interruption. Single doses of 80 mg/kg in iron overloaded thalassemic patients caused mild nausea and diarrhea noted. Acute signs of overdose may include nausea, vomiting, headache, and diarrhea. Overdose may be treated by induction of emesis or by gastric lavage, and by symptomatic treatment.

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In one clinical study, growth and sexual development of pediatric patients treated with EXJADE for up to 5 years were not affected. However, as a general precautionary measure in the management of pediatric patients with transfusional iron overload, body weight, height and sexual development should be monitored at regular intervals (every 12 months).

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