Sign Out
General: JADENU should not be combined with other iron chelator therapies as the safety and efficacy of such combinations has not been established.
No studies on the effects of deferasirox on the ability to drive or use machines have been performed. Patients experiencing dizziness should exercise caution when driving or operating machinery.
The decision to remove accumulated iron should be individualized based on anticipated clinical benefits and risks of chelation therapy (see Dosage & Administration).
Cardiovascular: Deferasirox has not been studied in patients with acute cardiac failure due to iron overload. Therefore, the use of JADENU is not recommended in these patients.
Ear/Nose/Throat: Auditory disturbances (high-frequency hearing loss, decreased hearing) have been reported with deferasirox therapy (see Adverse Reactions). Auditory testing is recommended before the start of JADENU treatment and thereafter at regular intervals.
Gastrointestinal: Gastrointestinal irritation may occur during JADENU 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 Adverse Reactions). Physicians and patients should remain alert for signs and symptoms of GI ulceration, perforation and haemorrhage during JADENU 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 JADENU in combination with drugs that have known ulcerogenic potential, such as NSAIDs, corticosteroids, or oral bisphosphonates, and in patients receiving anticoagulants (see Interactions).
Hematologic: There have been post-marketing reports (both spontaneous and from clinical trials) of cytopenias in patients treated with deferasirox. Most of these patients had preexisting hematologic disorders that are frequently associated with bone marrow failure (see Post-Market Adverse Drug Reactions under Adverse Reactions). The relationship of these episodes to treatment with deferasirox is unknown. In line with the standard clinical management of such hematological disorders, blood counts should be monitored regularly. Dose interruption of treatment with JADENU should be considered in patients who develop unexplained cytopenia. Reintroduction of therapy with JADENU may be considered, once the cause of the cytopenia has been elucidated.
Hepatic Biliary/Pancreatic: JADENU is not recommended in patients with severe hepatic impairment (Child-Pugh C) (see Pharmacology under Actions and Dosing Considerations under Dosage & Administration). Elevations of serum transaminase levels (greater than 5 times the upper limit of normal) have been observed in 40 patients receiving deferasirox. In these patients, the transaminase levels were already >5*ULN at baseline in 6 of the 40 patients. In 25 of the 40 patients, the transaminase levels at baseline were above the upper limit of normal but less than 5*ULN. There have been post-marketing reports of hepatic failure in patients treated with deferasirox. There are a total of 24 international reports of hepatic failure - 21 post-marketing reports and 3 reports from clinical studies. Two of the 24 cases were reported in Canada. Most reports of hepatic failure involved patients with significant comorbidities including liver cirrhosis and multi-organ failure; fatal outcomes were reported in some of these patients. As of the cut-off date above, no patient with normal baseline liver function or without additional life-threatening complications of their underlying disease has developed hepatic failure.
Although uncommon (0.3%), elevations of transaminases greater than 10 times the upper limit of the normal range, suggestive of hepatitis, have been observed in clinical trials. It is recommended that serum transaminases, bilirubin and alkaline phosphatase be monitored before the initiation of treatment, every 2 weeks during the first month and monthly thereafter. If there is an unexplained, persistent and progressive increase in serum transaminase levels, JADENU treatment should be interrupted.
In the clinical trial and post-marketing settings, cases of serious acute pancreatitis were observed with and without documented underlying biliary conditions. A causal association to deferasirox could not be ruled out.
Immune: Rare cases of serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving deferasirox, with the onset of the reaction occurring in the majority of cases within the first month of treatment (see Post-Market Adverse Drug Reactions under Adverse Reactions). If hypersensitivity reactions occur, JADENU should be discontinued and appropriate medical intervention instituted. JADENU should not be reintroduced in patients who have experienced previous hypersensitivity reactions on deferasirox due to the risk of anaphylactic shock.
Ophthalmologic: Ocular disturbances (lens opacities, early cataracts, maculopathies) have been reported with deferasirox therapy (see Adverse Reactions). Ophthalmic testing (including fundoscopy) is recommended before the start of JADENU treatment and thereafter at regular intervals.
Renal: Deferasirox has not been studied in patients with renal impairment. Deferasirox treatment has been initiated only in patients with serum creatinine within the age-appropriate normal range and therefore must be used with caution in patients with elevated serum creatinine levels (see Contraindications).
Deferasirox-treated patients experienced dose-dependent increases in serum creatinine. Increases in creatinine that were > 33% at ≥ 2 consecutive post baseline visits occurred at a greater frequency in deferasirox-treated patients compared to deferoxamine-treated patients (38% vs. 14%, respectively) in study 0107. In these beta-thalassemia patients, 94% of the creatinine elevations remained within the normal range. Under the dose adjustment instructions, dose reduction was required in one third of patients showing serum creatinine increase. In most patients undergoing dose reductions serum creatinine levels did not return to baseline; in 60% of patients undergoing dose reduction, serum creatinine remained elevated at > 33% without progression (see Abnormal Hematologic and Clinical Chemistry Findings under Adverse Reactions).
Cases of acute renal failure (some with fatal outcome) have been reported following the post-marketing use of deferasirox. There have been rare cases of acute renal failure requiring dialysis. For the fatal cases, it is impossible to completely exclude a contributory role of deferasirox to the renal impairment, although the fatalities in these critically ill patients could be attributable to other underlying diseases. The fact that there was an improvement after stopping the treatment in most of the cases with non-fatal acute renal failure is suggestive of a contributory role of deferasirox to these cases (see Post Market Adverse Drug Reactions under Adverse Reactions).
It is recommended that serum creatinine and/or creatinine clearance be assessed twice before initiating therapy. Weekly monitoring of serum creatinine and/or creatinine clearance is recommended in the first month after initiation or modification of therapy, and monthly thereafter. Patients with pre-existing renal conditions or patients who are receiving medicinal products that may depress renal function may be more at risk of complications. Care should be taken to maintain adequate hydration in patients (see Dosing Considerations under Dosage & Administration). Dose reduction, interruption, or discontinuations should be considered for elevations in serum creatinine (see Abnormal Hematologic and Clinical Chemistry Findings under Adverse Reactions).
Renal tubulopathy has been reported in patients treated with deferasirox. The majority of these patients were children and adolescents with beta-thalassemia and serum ferritin levels <1,500 μg/L.
Tests for proteinuria should be performed monthly. As needed, additional markers of renal tubular function (e.g. 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 there is a progressive increase in serum creatinine beyond the upper limit of normal, JADENU should be interrupted (see Dosage & Administration).
Skin: Serious skin reactions: Post-marketing cases of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and hypersensitivity vasculitis, and rare cases of erythema multiforme seen in the clinical trial setting, have occurred during treatment with deferasirox. Although no cases of DRESS (drug reaction with eosinophilia and systemic symptoms) have been confirmed, in view of the association of deferasirox with severe skin reactions, the risk of DRESS cannot be excluded. Upon suspicion of a serious skin reaction, JADENU should be discontinued immediately and should not be reintroduced.
Skin rashes: skin rashes may also appear during JADENU treatment. For rashes of mild to moderate severity, JADENU may be continued without dose adjustment, since the rash often resolves spontaneously. For more severe rash, where interruption of treatment may be necessary, JADENU may be re-introduced after resolution of the rash, at a lower dose followed by gradual dose escalation.
Monitoring and Laboratory Tests: Serum ferritin should be measured monthly to assess response to therapy and to evaluate for the possibility of overchelation of iron, although the correlation coefficient between serum ferritin and liver iron content (LIC) was 0.63, and changes in serum ferritin levels may not always reliably reflect changes in LIC. If the serum ferritin falls consistently below 500 μg/L, temporary interruption of JADENU therapy should be considered (see Dosage & Adminitration).
As with other iron chelator treatment, the risk of toxicity of JADENU may be increased when inappropriately given to patients with a low iron burden or with serum ferritin levels that are only slightly elevated.
It is recommended that serum transaminases, bilirubin and alkaline phosphatase be monitored before the initiation of treatment, every 2 weeks during the first month and monthly thereafter. It is recommended that serum creatinine be assessed twice before initiating therapy and monitored weekly for the first month followed by monthly thereafter (see Hepatic/Biliary/Pancreatic and Renal sections as previously mentioned).
Tests for proteinuria should be performed monthly (see Renal section as previously mentioned).
In line with standard clinical management of hematological disorders, blood counts should be monitored regularly (see Hematologic section as previously mentioned).
Carcinogenesis and Mutagenesis: See Pharmacology: Toxicology: Mutagenicity and Carcinogenicity under Actions.
Use in children (2 to 16 years of age): There are limited data on the safety and effectiveness of deferasirox in pediatric patients aged 2 to 5 (see Pharmacology: Pharmacodynamics: Clinical trials under Actions). Deferasirox has not been associated with growth retardation in children followed for up to 5 years in clinical trials. However, as a precautionary measure, body weight and longitudinal growth in pediatric patients should be monitored at regular intervals (every 12 months).
Use in elderly (≥ 65 years of age): Four hundred and thirty-one (431) patients ≥ 65 years of age have been studied in clinical trials of deferasirox. The majority of these patients had myelodysplastic syndrome (MDS, n= 393; β-thalassemia, n= 2; other anemias, n= 36). In general, caution should be used in elderly patients due to the greater frequency of decreased hepatic, renal, or cardiac function, concomitant disease or other drug therapy. 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.
