• Home
  • A-B index
  • Pharmacological Index
  • Drug Classes
  • Active Ingredients
  • Companies
  • News
  • Exjade
    / Novartis


    Active Ingredient
    Deferasirox 125, 250, 500 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Dispersible Tablet

    28 X 125 mg

    partial basket chart 67378 5423

    Dispersible Tablet

    28 X 250 mg

    partial basket chart 67379 5424

    Dispersible Tablet

    28 X 500 mg

    partial basket chart 67381 5425

    Related information


    Dosage

    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 microgram/L). Caution should be taken during chelation therapy to minimise the risk of over-chelation in all patients.
    Transfusional iron overload: The recommended initial daily dose of the product is 20 mg/kg body weight. It is recommended that serum ferritin be monitored every month. Every 3 to 6 months of treatment, consider a dose increase in increments of 5 to 10 mg/kg if the patient’s LIC is ≥7 mg Fe/g dw, or serum ferritin is consistently >2,000 microgram/L and not showing a downward trend, and the patient is tolerating the drug 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 microgram/L, dosing should not exceed 10 mg/kg. For patients in whom the dose was increased to >10 mg/kg, dose reduction is recommended to 10 mg/kg or less when LIC is <7 mg Fe/g dw or serum ferritin is ≤2,000 microgram/L. Once a satisfactory body iron level has been achieved (LIC <3 mg Fe/g dw or serum ferritin <300 microgram/L), treatment should be interrupted. Treatment should be re-initiated when there is evidence from clinical monitoring that chronic iron overload is present.
    Non-transfusion-dependent thalassemia syndromes: The recommended initial daily dose of EXJADE in patients with non-transfusion-dependent thalassaemia syndromes is 10 mg/kg body weight. 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.
    Special populations
    Patients with renal impairment:
    The drug has not been studied in patients with renal impairment and is contraindicated in patients with estimated creatinine clearance <60 ml/min.
    Patients with hepatic impairment: The drug 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 the drug 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.
    Pediatric patients: The dosing recommendations for paediatric patients aged 2 to 17 years with transfusional iron overload are the same as for adult patients. Changes in weight of paediatric 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 paediatric patients with non-transfusion-dependent thalassaemia 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.
    Elderly patients: The dosing recommendations for elderly patients are the same as described above. In clinical trials, elderly patients experienced a higher frequency of adverse reactions than younger patients (in particular, diarrhoea) and should be monitored closely for adverse reactions that may require a dose adjustment.
    Method of administration: 
    For oral use. This product must be taken once daily on an empty stomach at least 30 minutes before food, preferably at the same time each day.


    Indications

    The product is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional haemosiderosis) in adult and pediatric patients (aged 2 years and over). The drug is also indicated for the treatment of chronic iron overload in patients with non-transfusion-dependent thalassemia syndromes aged 10 years and older. 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.


    Contra-Indications

    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.


    Special Precautions

    The goals of iron chelation therapy are to remove the amount of iron administered in transfusions and, as required, to reduce the existing iron burden. The decision to administer iron chelation therapy should take into account the risk-benefit ratio for the individual patient. Caution should be used in elderly patients due to a higher frequency of adverse reactions.
    Kidneys: During clinical studies, dose-dependent increases in serum creatinine were observed in some patients treated with Exjade. In one such clinical study, serum creatinine increases of > 33% were noted at two consecutive measurements in 38% of patients taking deferasirox (Exjade) and 14% of patients taking deferoxamine. Cases of acute renal failure, some with fatal outcome, have been reported during postmarketing use of Exjade. While it is true that a connection between Exjade and renal impairment cannot be fully ruled out in the cases with a fatal outcome, the fatal outcome is probably a consequence of the underlying condition of these severely ill patients. The fact that there was an improvement in renal function in most of the non-fatal cases following withdrawal of treatment indicates an involvement of Exjade in the acute renal failure. There have been rare cases of acute renal failure requiring dialysis. Non-progressive rises in serum creatinine, have been noted in patients treated with Exjade, usually within the normal range. It is recommended that serum creatinine and/or creatinine clearance be measured twice before initiating therapy.
    For full detail see prescribing information.
    Liver: Liver function test elevations have been observed in patients treated with EXJADE. Post-marketing cases of hepatic failure, sometimes fatal, have been reported in patients treated with EXJADE. Most reports of hepatic failure involved patients with significant morbidities including pre-existing liver cirrhosis. However, the role of EXJADE as a contributing or aggravating factor cannot be excluded. 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. If there is a persistent and progressive increase in serum transaminase levels that cannot be attributed to other causes, should be interrupted.
    For full detail see prescribing information.
    Gastrointestinal effects: Gastrointestinal irritation may occur during treatment. Upper gastrointestinal ulcers and hemorrhage have been reported in patients, including children and adolescents. There have been rare reports of fatal GI hemorrhages, especially in elderly patients who had advanced hematologic malignancies and/or low platelet counts. Multiple ulcers have been observed in some patients. Physicians and patients should remain alert for signs and symptoms of gastrointestinal ulcers and hemorrhage during therapy. Further evaluation and appropriate treatment should be initiated immediately if a serious gastrointestinal adverse event is suspected. Caution is required in patients taking this drug in combination with medicinal products that have known ulcerogenic potential (such as NSAIDs, corticosteroids, or oral bisphosphonates), in patients using anticoagulants, and in patients with platelet counts <50 x 109/L.
    Skin: Skin rashes may appear. For rashes of mild to moderate severity, may be continued without dose adjustment, since the rash often resolves spontaneously. For more severe rash, where interruption of treatment may be necessary, this drug may be reintroduced after resolution of the rash at a lower dose, followed by gradual dose escalation. In severe cases, this reintroduction may be conducted in combination with a short course of oral corticosteroids. Rare cases of erythema multiforme have been reported.
    Hypersensitivity reactions: Rare cases of serious hypersensitivity reactions (such as anaphylaxis and angioedema), occurring in most cases within the first month of treatment, have been reported in patients. In the event of severe reactions, the usual appropriate medical measures must be taken and treatment with  must be discontinued.
    Eyes and Ears: Disturbances of hearing (decreased hearing) and vision (lens opacities) have been reported. Auditory and ophthalmic testing (including fundoscopy) are recommended before the start of Exjade treatment and at regular intervals thereafter (every 12 months). If disturbances are noted, dose reduction or withdrawal of the drug may be considered.
    Haematological disorders: There have been post-marketing reports (both spontaneous and from clinical trials) of cytopenias in patients treated with Exjade. Most of these patients had pre-existing haematologic disorders that are potentially associated with bone marrow failure. The relationship of these episodes to treatment with Exjade is uncertain. In line with the standard clinical management of such hematological disorders, peripheral blood counts should be regularly performed. Interruption of treatment should be considered in patients who develop unexplained cytopenia. Re-introduction of therapy may be considered, once the cause of the cytopenia has been elucidated and an association excluded with adequate certainty.
    General precautions: As with other iron chelator treatment, the risk of toxicity may be increased when excessively high doses are given in patients with a low iron burden or with serum ferritin levels that are only slightly elevated. Exjade has not been associated with growth retardation in children followed for up to 5 years in clinical trials. However, as a general precautionary measure, bodyweight and longitudinal growth should be monitored at regular intervals (every 12 months) in paediatric patients. No data are available at present on the frequency of sickle cell crises, as compared with the frequency of such crises in patients not receiving chelator therapy. Exjade has not been studied in patients with aluminium overload and should not be used in this indication. Exjade must not be combined with other iron chelator therapies as the safety of such combinations has not been established. The tablets contain lactose (1.1 mg lactose for each mg of deferasirox). This medicine is not recommended in patients with rare hereditary problems of galactose intolerance, of severe lactase deficiency or of glucose-galactose malabsorption.
    For full details see prescribing information.


    Side Effects

    Headache, diarrhea, constipation, vomiting, nausea, abdominal pain, abdominal distension, dyspepsia. Elevated transaminases. Rash, pruritus. Proteinuria, serum creatinine increased.
    For full details see prescribing information.


    Drug interactions

    Decreasing drug systemic exposure-rifampicin, phenytoin, phenobarbital, ritonavir, Agents metabolized by CYP3A4-ciclosporin, simvastatin, hormonal contraceptive agents, midazolam, Agents metabolized by CYP2C8- repaglinide, Agents metabolized by CYP1A2- theophylline, clozapine, izanidine.
    See prescribing information for full details.  


    Pregnancy and Lactation

    Pregnancy: The potential risk for humans is unknown. It is therefore recommended that the drug should not be used during pregnancy unless absolutely necessary.
    Lactation: Breastfeeding is not recommended during treatment with the drug.
    See prescribing information for full details.   


    Overdose

    Cases of overdose (2-3 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 thalassaemic patients have been tolerated, with only mild nausea and diarrhoea noted .Single doses up to 40 mg/kg in normal subjects have been well tolerated. Possible acute signs of overdose are nausea, vomiting, headache and diarrhoea. Overdose may be treated by induction of emesis or by gastric lavage, and by symptomatic treatment.
    See prescribing information for full details.


    Important notes

    The bioavailability of deferasirox was increased to a variable extent when taken along with food.
    No interaction was observed between the product and digoxin. An interval of 2 hours should be observed between ingestion of the drug tablets and of aluminium-containing antacid preparations.
    Bodyweight and longitudinal growth should be monitored at regular intervals (every 12 months) in paediatric patients.
    Storage: Do not store above 30°C. Store in the original package in order to protect from moisture.


    Manufacturer
    Novartis Pharma Stein AG Switzerland
    Licence holder
    CLOSE