FDA label 63ac2e2f-5187-8663-e053-2a91aa0a15a8

WARNING: RENAL FAILURE, HEPATIC FAILURE, AND GASTROINTESTINAL HEMORRHAGE Renal Failure JADENU can cause acute renal failure and death, particularly in patients with comorbidities and those who are in the advanced stages of their hematologic disorders. Measure serum creatinine and determine creatinine clearance (CLcr) in duplicate prior to initiation of therapy and monitor renal function at least monthly thereafter. For patients with baseline renal impairment or increased risk of acute renal failure, monitor creatinine weekly for the first month, then at least monthly. Consider dose reduction, interruption, or discontinuation based on increases in serum creatinine [see Dosage and Administration (2.4, 2.5), Warnings and Precautions (5.1)] . Hepatic Failure JADENU can cause hepatic injury including hepatic failure and death. Measure serum transaminases and bilirubin in all patients prior to initiating treatment, every 2 weeks during the first month, and at least monthly thereafter. Avoid use of JADENU in patients with severe (Child-Pugh C) hepatic impairment and reduce the dose in patients with moderate (Child Pugh B) hepatic impairment [see Dosage and Administration (2.4), Warnings and Precautions (5.2)] . Gastrointestinal Hemorrhage JADENU can cause gastrointestinal (GI) hemorrhages, which may be fatal, especially in elderly patients who have advanced hematologic malignancies and/or low platelet counts. Monitor patients and discontinue JADENU for suspected GI ulceration or hemorrhage [see Warnings and Precautions (5.3)] . WARNING: RENAL FAILURE, HEPATIC FAILURE, AND GASTROINTESTINAL HEMORRHAGE See full prescribing information for complete boxed warning. JADENU may cause serious and fatal: renal toxicity, including failure ( 5.1 ) hepatic toxicity, including failure ( 5.2 ) gastrointestinal hemorrhage ( 5.3 ) JADENU therapy requires close patient monitoring, including laboratory tests of renal and hepatic function. ( 5 )

5 WARNINGS AND PRECAUTIONS Bone marrow suppression: Neutropenia, agranulocytosis, worsening anemia, and thrombocytopenia, including fatal events; monitor blood counts during JADENU therapy. Interrupt therapy for toxicity. ( 5.4 ) Increased Toxicity in the Elderly: Monitor closely for toxicity. ( 5.5 ) Hypersensitivity Reactions: Discontinue JADENU for severe reactions and institute medical intervention. ( 5.6 ) Severe skin reactions including Stevens-Johnson syndrome: Discontinue JADENU. ( 5.7 ) 5.1 Renal Toxicity, Renal Failure, and Proteinuria JADENU can cause acute renal failure, fatal in some patients and requiring dialysis in others. Postmarketing experience showed that most fatalities occurred in patients with multiple comorbidities and who were in advanced stages of their hematological disorders. In the clinical trials, deferasirox-treated patients experienced dose-dependent increases in serum creatinine. In patients with transfusional iron overload, these increases in creatinine occurred at a greater frequency compared to deferoxamine-treated patients (38% versus 14%, respectively, in Study 1 and 36% versus 22%, respectively, in Study 3) [see Adverse Reactions (6.1, 6.2)] . Measure serum creatinine in duplicate (due to variations in measurements) and determine the CLcr (estimated by the Cockcroft-Gault method) before initiating therapy in all patients in order to establish a reliable pretreatment baseline. Monitor serum creatinine weekly during the first month after initiation or modification of therapy and at least monthly thereafter. Monitor serum creatinine and/or CLcr more frequently if creatinine levels are increasing. Dose reduction, interruption, or discontinuation based on increases in serum creatinine may be necessary [see Dosage and Administration (2.5)] . JADENU is contraindicated in patients with CLcr less than 40 mL/minute or serum creatinine greater than 2 times the age appropriate ULN. Renal tubular damage, including Fanconi’s Syndrome, has been reported in patients treated with deferasirox, most commonly in children and adolescents with beta-thalassemia and serum ferritin levels less than 1500 mcg/L. Intermittent proteinuria (urine protein/creatinine ratio greater than 0.6 mg/mg) occurred in 18.6% of deferasirox-treated patients compared to 7.2% of deferoxamine-treated patients in Study 1. In clinical trials in patients with transfusional iron overload, deferasirox was temporarily withheld until the urine protein/creatinine ratio fell below 0.6 mg/mg. Monthly monitoring for proteinuria is recommended. The mechanism and clinical significance of the proteinuria are uncertain [see Adverse Reactions (6.1)] . 5.2 Hepatic Toxicity and Failure Deferasirox can cause hepatic injury, fatal in some patients. In Study 1, 4 patients (1.3%) discontinued deferasirox because of hepatic toxicity (drug-induced hepatitis in 2 patients and increased serum transaminases in 2 additional patients). Hepatic toxicity appears to be more common in patients greater than 55 years of age. Hepatic failure was more common in patients with significant comorbidities, including liver cirrhosis and multiorgan failure [see Adverse Reactions (6.1)] . Measure transaminases (AST and ALT) and bilirubin in all patients before the initiation of treatment and every 2 weeks during the first month and at least monthly thereafter. Consider dose modifications or interruption of treatment for severe or persistent elevations. Avoid the use of JADENU in patients with severe (Child-Pugh C) hepatic impairment. Reduce the starting dose in patients with moderate (Child-Pugh B) hepatic impairment [see Dosage and Administration (2.4), Use in Specific Populations (8.7)] . Patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment may be at higher risk for hepatic toxicity. 5.3 Gastrointestinal (GI) Ulceration, Hemorrhage, and Perforation GI hemorrhage, including deaths, has been reported, especially in elderly patients who had advanced hematologic malignancies and/or low platelet counts. Nonfatal upper GI irritation, ulceration and hemorrhage have been reported in patients, including children and adolescents, receiving deferasirox [see Adverse Reactions (6.1)] . Monitor for signs and symptoms of GI ulceration and hemorrhage during JADENU therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. The risk of gastrointestinal hemorrhage may be increased when administering JADENU in combination with drugs that have ulcerogenic or hemorrhagic potential, such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, oral bisphosphonates, or anticoagulants. There have been reports of ulcers complicated with gastrointestinal perforation (including fatal outcome) [see Adverse Reactions (6.2)] . 5.4 Bone Marrow Suppression Neutropenia, agranulocytosis, worsening anemia, and thrombocytopenia, including fatal events, have been reported in patients treated with deferasirox. Preexisting hematologic disorders may increase this risk. Monitor blood counts in all patients. Interrupt treatment with JADENU in patients who develop cytopenias until the cause of the cytopenia has been determined. JADENU is contraindicated in patients with platelet counts below 50 x 10 9 /L. 5.5 Increased Risk of Toxicity in the Elderly Deferasirox has been associated with serious and fatal adverse reactions in the postmarketing setting, predominantly in elderly patients. Monitor elderly patients treated with JADENU more frequently for toxicity [see Use in Specific Populations (8.5)] . 5.6 Hypersensitivity JADENU may cause serious hypersensitivity reactions (such as anaphylaxis and angioedema), with the onset of the reaction usually occurring within the first month of treatment [see Adverse Reactions (6.2)]. If reactions are severe, discontinue JADENU and institute appropriate medical intervention. JADENU is contraindicated in patients with known hypersensitivity to deferasirox products and should not be reintroduced in patients who have experienced previous hypersensitivity reactions on deferasirox products due to the risk of anaphylactic shock. 5.7 Severe Skin Reactions Severe skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and erythema multiforme, have been reported during deferasirox therapy [see Adverse Reactions (6.2)] . The risk of other skin reactions including DRESS (drug reaction with eosinophilia and systemic symptoms) cannot be excluded. If severe skin reactions are suspected, discontinue JADENU immediately and do not reintroduce JADENU therapy. 5.8 Skin Rash Rashes may occur during JADENU treatment [see Adverse Reactions (6.1)] . For rashes of mild to moderate severity, JADENU may be continued without dose adjustment, since the rash often resolves spontaneously. In severe cases, interrupt treatment with JADENU. Reintroduction at a lower dose with escalation may be considered after resolution of the rash. 5.9 Auditory and Ocular Abnormalities Auditory disturbances (high frequency hearing loss, decreased hearing), and ocular disturbances (lens opacities, cataracts, elevations in intraocular pressure, and retinal disorders) were reported at a frequency of less than 1% with deferasirox therapy in the clinical studies. Perform auditory and ophthalmic testing (including slit lamp examinations and dilated fundoscopy) before starting JADENU treatment and thereafter at regular intervals (every 12 months). If disturbances are noted, monitor more frequently. Consider dose reduction or interruption. 5.10 Overchelation For patients with transfusional iron overload, measure serum ferritin monthly to assess for possible overchelation of iron. If the serum ferritin falls below 500 mcg/L, consider interrupting therapy with JADENU, since overchelation may increase JADENU toxicity [see Dosage and Administration (2.1)] . For patients with NTDT, measure LIC by liver biopsy or by using an FDA-cleared or approved method for monitoring patients receiving deferasirox therapy every 6 months on treatment. Interrupt JADENU administration when the LIC is less than 3 mg Fe/g dw. Measure serum ferritin monthly, and if the serum ferritin falls below 300 mcg/L, interrupt JADENU and obtain a confirmatory LIC [see Clinical Studies (14)] .

6 ADVERSE REACTIONS The following adverse reactions are also discussed in other sections of the labeling: Renal Toxicity, Renal Failure, and Proteinuria [see Warnings and Precautions (5.1)] Hepatic Toxicity and Failure [see Warnings and Precautions (5.2)] Gastrointestinal (GI) Hemorrhage [see Warnings and Precautions (5.3)] Bone Marrow Suppression [see Warnings and Precautions (5.4)] Hypersensitivity [see Warnings and Precautions (5.6)] Severe Skin Reactions [see Warnings and Precautions (5.7)] Skin Rash [see Warnings and Precautions (5.8)] Auditory and Ocular Abnormalities [see Warnings and Precautions (5.9)] In patients with transfusional iron overload, the most frequently occurring (greater than 5%) adverse reactions are diarrhea, vomiting, nausea, abdominal pain, skin rashes, and increases in serum creatinine. In deferasirox-treated patients with NTDT syndromes, the most frequently occurring (greater than 5%) adverse reactions are diarrhea, rash and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. JADENU was evaluated in healthy volunteer trials. Currently, there are no clinical data in patients with JADENU tablets and JADENU Sprinkle granules. JADENU contains the same active ingredient as Exjade (deferasirox) tablets for oral suspension. The following adverse reactions have been reported with Exjade tablets for oral suspension. Transfusional Iron Overload A total of 700 adult and pediatric patients were treated with deferasirox for 48 weeks in premarketing studies. These included 469 patients with beta-thalassemia, 99 with rare anemias, and 132 with sickle cell disease. Of these patients, 45% were male, 70% were Caucasian and 292 patients were less than 16 years of age. In the sickle cell disease population, 89% of patients were black. Median treatment duration among the sickle cell patients was 51 weeks. Of the 700 patients treated, 469 (403 beta-thalassemia and 66 rare anemias) were entered into extensions of the original clinical protocols. In ongoing extension studies, median durations of treatment were 88 to 205 weeks. Six hundred twenty-seven patients with MDS were enrolled across 5 uncontrolled trials. These studies varied in duration from 1 to 5 years. The discontinuation rate across studies in the first year was 46% (AEs 20%, withdrawal of consent 10%, death 8%, other 4%, lab abnormalities 3%, and lack of efficacy 1%). Among 47 patients enrolled in the study of 5-year duration, 10 remained on deferasirox at the completion of the study. Table 1 displays adverse reactions occurring in greater than 5% of deferasirox-treated beta-thalassemia patients (Study 1), sickle cell disease patients (Study 3), and patients with MDS (MDS pool). Abdominal pain, nausea, vomiting, diarrhea, skin rashes, and increases in serum creatinine were the most frequent adverse reactions reported with a suspected relationship to deferasirox. Gastrointestinal symptoms, increases in serum creatinine, and skin rash were dose related. Table 1. Adverse Reactions* Occurring in >5% of Deferasirox-treated Patients in Study 1, Study 3, and MDS Pool *Adverse reaction frequencies are based on adverse events reported regardless of relationship to study drug. **Includes ‘abdominal pain’, ‘abdominal pain lower’, and ‘abdominal pain upper’ which were reported as adverse events. ***Includes ‘blood creatinine increased’ and ‘blood creatinine abnormal’ which were reported as adverse events. Also see Table 2. Study 1 (Beta-thalassemia) Study 3 (Sickle Cell Disease) MDS Pool Preferred Term Deferasirox N=296 n (%) Deferoxamine N=290 n (%) Deferasirox N=132 n (%) Deferoxamine N=63 n (%) Deferasirox N=627 n (%) Abdominal Pain** 63 (21) 41 (14) 37 (28) 9 (14) 145 (23) Diarrhea 35 (12) 21 (7) 26 (20) 3 (5) 297 (47) Creatinine Increased*** 33 (11) 0 (0) 9 (7) 0 89 (14) Nausea 31 (11) 14 (5) 30 (23) 7 (11) 161 (26) Vomiting 30 (10) 28 (10) 28 (21) 10 (16) 83 (13) Rash 25 (8) 9 (3) 14 (11) 3 (5) 83 (13) In Study 1, a total of 113 (38%) patients treated with deferasirox had increases in serum creatinine greater than 33% above baseline on 2 separate occasions (Table 2) and 25 (8%) patients required dose reductions. Increases in serum creatinine appeared to be dose related [see Warnings and Precautions (5.1)] . In this study, 17 (6%) patients treated with deferasirox developed elevations in SGPT/ALT levels greater than 5 times the ULN at 2 consecutive visits. Of these, 2 patients had liver biopsy proven drug-induced hepatitis and both discontinued deferasirox therapy [see Warnings and Precautions (5.2)] . An additional 2 patients, who did not have elevations in SGPT/ALT greater than 5 times the ULN, discontinued deferasirox because of increased SGPT/ALT. Increases in transaminases did not appear to be dose related. Adverse reactions that led to discontinuations included abnormal liver function tests (2 patients) and drug-induced hepatitis (2 patients), skin rash, glycosuria/proteinuria, Henoch Schönlein purpura, hyperactivity/insomnia, drug fever, and cataract (1 patient each). In Study 3, a total of 48 (36%) patients treated with deferasirox had increases in serum creatinine greater than 33% above baseline on 2 separate occasions (Table 2) [see Warnings and Precautions (5.1)] . Of the patients who experienced creatinine increases in Study 3, 8 deferasirox-treated patients required dose reductions. In this study, 5 patients in the deferasirox group developed elevations in SGPT/ALT levels greater than 5 times the ULN at 2 consecutive visits and 1 patient subsequently had deferasirox permanently discontinued. Four additional patients discontinued due to adverse reactions with a suspected relationship to study drug, including diarrhea, pancreatitis associated with gallstones, atypical tuberculosis, and skin rash. In the MDS pool, in the first year, a total of 229 (37%) patients treated with deferasirox had increases in serum creatinine greater than 33% above baseline on 2 consecutive occasions (Table 2) and 8 (3.5%) patients permanently discontinued [see Warnings and Precautions (5.1)] . A total of 5 (0.8%) patients developed SGPT/ALT levels greater than 5 times the ULN at 2 consecutive visits. The most frequent adverse reactions that led to discontinuation included increases in serum creatinine, diarrhea, nausea, rash, and vomiting. Death was reported in the first year in 52 (8%) of patients [see Clinical Studies (14)] . Table 2. Number (%) of Patients with Increases in Serum Creatinine or SGPT/ALT in Study 1, Study 3, and MDS Pool Study 1 (Beta-thalassemia) Study 3 (Sickle Cell Disease) MDS Pool Laboratory Parameter Deferasirox N=296 n (%) Deferoxamine N=290 n (%) Deferasirox N=132 n (%) Deferoxamine N=63 n (%) Deferasirox N=627 n (%) Serum Creatinine Creatinine increase >33% at 2 consecutive postbaseline visits 113 (38) 41 (14) 48 (36) 14 (22) 229 (37) Creatinine increase >33% and >ULN at 2 consecutive postbaseline visits 7 (2) 1 (0) 3 (2) 2 (3) 126 (20) SGPT/ALT SGPT/ALT >5 x ULN at 2 postbaseline visits 25 (8) 7 (2) 2 (2) 0 9 (1) SGPT/ALT >5 x ULN at 2 consecutive postbaseline visits 17 (6) 5 (2) 5 (4) 0 5 (1) Non-Transfusion-Dependent Thalassemia Syndromes In Study 4, 110 patients with NTDT received 1 year of treatment with deferasirox 5 or 10 mg/kg/day and 56 patients received placebo in a double-blind, randomized trial. In Study 5, 130 of the patients who completed Study 4 were treated with open-label deferasirox at 5, 10, or 20 mg/kg/day (depending on the baseline LIC) for 1 year [see Clinical Studies (14)] . Table 3 displays adverse reactions occurring in greater than 5% in any group. The most frequent adverse reactions with a suspected relationship to study drug were nausea, rash, and diarrhea. Table 3. Adverse Reactions Occurring in >5% in NTDT Patients Study 4 Study 5 Deferasirox Placebo Deferasirox N=110 N=56 N=130 n (%) n (%) n (%) Any adverse reaction 31 (28) 9 (16) 27 (21) Nausea 7 (6) 4 (7) 2 (2) Rash 7 (6) 1 (2) 2 (2) Diarrhea 5 (5) 1 (2) 7 (5) In Study 4, 1 patient in the placebo 10 mg/kg/day group experienced an ALT increase to greater than 5 times ULN and greater than 2 times baseline (Table 4). Three deferasirox-treated patients (all in the 10 mg/kg/day group) had 2 consecutive serum creatinine level increases greater than 33% from baseline and greater than ULN. Serum creatinine returned to normal in all 3 patients (in 1 spontaneously and in the other 2 after drug interruption). Two additional cases of ALT increase and 2 additional cases of serum creatinine increase were observed in the 1-year extension of Study 4. Table 4. Number (%) of NTDT Patients with Increases in Serum Creatinine or SGPT/ALT Study 4 Study 5 Deferasirox Placebo Deferasirox N=110 N=56 N=130 Laboratory Parameter n (%) n (%) n (%) Serum creatinine (>33% increase from baseline and >ULN at ≥2 consecutive postbaseline values) 3 (3) 0 2 (2) SGPT/ALT (>5 x ULN and >2 x baseline) 1 (1) 1 (2) 2 (2) Proteinuria In clinical studies, urine protein was measured monthly. Intermittent proteinuria (urine protein/creatinine ratio greater than 0.6 mg/mg) occurred in 18.6% of deferasirox-treated patients compared to 7.2% of deferoxamine-treated patients in Study 1 [see Warnings and Precautions (5.1)] . Other Adverse Reactions In the population of more than 5,000 patients with transfusional iron overload who have been treated with deferasirox during clinical trials, adverse reactions occurring in 0.1% to 1% of patients included gastritis, edema, sleep disorder, pigmentation disorder, dizziness, anxiety, maculopathy, cholelithiasis, pyrexia, fatigue, laryngeal pain, cataract, hearing loss, gastrointestinal hemorrhage, gastric ulcer (including multiple ulcers), duodenal ulcer, renal tubular disorder (Fanconi’s syndrome), and acute pancreatitis (with and without underlying biliary conditions). Adverse reactions occurring in 0.01% to 0.1% of patients included optic neuritis, esophagitis, and erythema multiforme. Adverse reactions which most frequently led to dose interruption or dose adjustment during clinical trials were rash, gastrointestinal disorders, infections, increased serum creatinine, and increased serum transaminases. 6.2 Postmarketing Experience The following adverse reactions have been spontaneously reported during post-approval use of deferasirox in the transfusional iron overload setting. Because these reactions are reported voluntarily from a population of uncertain size, in which patients may have received concomitant medication, it is not always possible to reliably estimate frequency or establish a causal relationship to drug exposure. Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome (SJS), leukocytoclastic vasculitis, urticaria, alopecia, toxic epidermal necrolysis (TEN) Immune system disorders: hypersensitivity reactions (including anaphylactic reaction and angioedema) Renal and urinary disorders: acute renal failure, tubulointerstitial nephritis Hepatobiliary disorders: hepatic failure Gastrointestinal disorders: gastrointestinal perforation Blood and lymphatic system disorders: worsening anemia

<table> <caption>Table 1. Adverse Reactions* Occurring in &gt;5% of Deferasirox-treated Patients in Study 1, Study 3, and MDS Pool</caption> <col width="200"/> <col width="150"/> <col width="150"/> <col width="150"/> <col width="150"/> <col width="150"/> <tfoot> <tr> <td colspan="6" styleCode="Toprule Lrule Rrule Botrule ">*Adverse reaction frequencies are based on adverse events reported regardless of relationship to study drug. **Includes &#x2018;abdominal pain&#x2019;, &#x2018;abdominal pain lower&#x2019;, and &#x2018;abdominal pain upper&#x2019; which were reported as adverse events. ***Includes &#x2018;blood creatinine increased&#x2019; and &#x2018;blood creatinine abnormal&#x2019; which were reported as adverse events. Also see Table 2. </td> </tr> </tfoot> <tbody> <tr> <td styleCode="Toprule Lrule Rrule " valign="bottom"/> <td colspan="2" align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Study 1 (Beta-thalassemia) </content> </td> <td colspan="2" align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Study 3 (Sickle Cell Disease) </content> </td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">MDS Pool</content> </td> </tr> <tr> <td styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Preferred Term</content> </td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Deferasirox</content> <content styleCode="bold">N=296</content> <content styleCode="bold">n (%)</content> </td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Deferoxamine</content> <content styleCode="bold">N=290</content> <content styleCode="bold">n (%)</content> </td> <td align="center" styleCode="Toprule Lrule Rrule "> <content styleCode="bold">Deferasirox</content> <content styleCode="bold">N=132</content> <content styleCode="bold">n (%)</content> </td> <td align="center" styleCode="Toprule Lrule Rrule "> <content styleCode="bold">Deferoxamine</content> <content styleCode="bold">N=63</content> <content styleCode="bold">n (%)</content> </td> <td align="center" styleCode="Toprule Lrule Rrule "> <content styleCode="bold">Deferasirox</content> <content styleCode="bold">N=627</content> <content styleCode="bold">n (%)</content> </td> </tr> <tr> <td styleCode="Toprule Lrule Rrule " valign="bottom">Abdominal Pain**</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">63 (21)</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">41 (14)</td> <td align="center" styleCode="Toprule Lrule Rrule ">37 (28)</td> <td align="center" styleCode="Toprule Lrule Rrule ">9 (14)</td> <td align="center" styleCode="Toprule Lrule Rrule ">145 (23)</td> </tr> <tr> <td styleCode="Toprule Lrule Rrule " valign="bottom">Diarrhea</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">35 (12)</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">21 (7)</td> <td align="center" styleCode="Toprule Lrule Rrule ">26 (20)</td> <td align="center" styleCode="Toprule Lrule Rrule ">3 (5)</td> <td align="center" styleCode="Toprule Lrule Rrule ">297 (47)</td> </tr> <tr> <td styleCode="Toprule Lrule Rrule " valign="bottom">Creatinine Increased***</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">33 (11)</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">0 (0)</td> <td align="center" styleCode="Toprule Lrule Rrule ">9 (7)</td> <td align="center" styleCode="Toprule Lrule Rrule ">0</td> <td align="center" styleCode="Toprule Lrule Rrule ">89 (14)</td> </tr> <tr> <td styleCode="Toprule Lrule Rrule " valign="bottom">Nausea</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">31 (11)</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">14 (5)</td> <td align="center" styleCode="Toprule Lrule Rrule ">30 (23)</td> <td align="center" styleCode="Toprule Lrule Rrule ">7 (11)</td> <td align="center" styleCode="Toprule Lrule Rrule ">161 (26)</td> </tr> <tr> <td styleCode="Toprule Lrule Rrule " valign="bottom">Vomiting</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">30 (10)</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">28 (10)</td> <td align="center" styleCode="Toprule Lrule Rrule ">28 (21)</td> <td align="center" styleCode="Toprule Lrule Rrule ">10 (16)</td> <td align="center" styleCode="Toprule Lrule Rrule ">83 (13)</td> </tr> <tr> <td styleCode="Toprule Lrule Rrule " valign="bottom">Rash</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">25 (8)</td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom">9 (3)</td> <td align="center" styleCode="Toprule Lrule Rrule ">14 (11)</td> <td align="center" styleCode="Toprule Lrule Rrule ">3 (5)</td> <td align="center" styleCode="Toprule Lrule Rrule ">83 (13)</td> </tr> </tbody> </table>

<table> <caption>Table 2. Number (%) of Patients with Increases in Serum Creatinine or SGPT/ALT in Study 1, Study 3, and MDS Pool</caption> <col width="225"/> <col width="125"/> <col width="125"/> <col width="125"/> <col width="125"/> <col width="125"/> <tbody> <tr> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom"/> <td colspan="2" align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Study 1 (Beta-thalassemia) </content> </td> <td colspan="2" align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Study 3 (Sickle Cell Disease) </content> </td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">MDS Pool</content> </td> </tr> <tr> <td styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Laboratory Parameter</content> </td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Deferasirox</content> <content styleCode="bold">N=296</content> <content styleCode="bold">n (%)</content> </td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Deferoxamine</content> <content styleCode="bold">N=290</content> <content styleCode="bold">n (%)</content> </td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Deferasirox</content> <content styleCode="bold">N=132</content> <content styleCode="bold">n (%)</content> </td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Deferoxamine</content> <content styleCode="bold">N=63</content> <content styleCode="bold">n (%)</content> </td> <td align="center" styleCode="Toprule Lrule Rrule " valign="bottom"> <content styleCode="bold">Deferasirox</content> <content styleCode="bold">N=627</content> <content styleCode="bold">n (%)</content> </td> </tr> <tr> <td colspan="6" styleCode="Toprule Lrule Rrule "> <content styleCode="bold">Serum Creatinine</content> </td> </tr> <tr> <td align="left" styleCode="Toprule Lrule Rrule " valign="bottom">Creatinine increase &gt;33% at 2 consecutive postbaseline visits</td> <td align="center" styleCode="Toprule Lrule Rrule ">113 (38)</td> <td align="center" styleCode="Toprule Lrule Rrule ">41 (14)</td> <td align="center" styleCode="Toprule Lrule Rrule ">48 (36)</td> <td align="center" styleCode="Toprule Lrule Rrule ">14 (22)</td> <td align="center" styleCode="Toprule Lrule Rrule ">229 (37)</td> </tr> <tr> <td align="left" styleCode="Toprule Lrule Rrule " valign="bottom">Creatinine increase &gt;33% and &gt;ULN at 2 consecutive postbaseline visits</td> <td align="center" styleCode="Toprule Lrule Rrule ">7 (2)</td> <td align="center" styleCode="Toprule Lrule Rrule ">1 (0)</td> <td align="center" styleCode="Toprule Lrule Rrule ">3 (2)</td> <td align="center" styleCode="Toprule Lrule Rrule ">2 (3)</td> <td align="center" styleCode="Toprule Lrule Rrule ">126 (20)</td> </tr> <tr> <td colspan="6" styleCode="Toprule Lrule Rrule "> <content styleCode="bold">SGPT/ALT</content> </td> </tr> <tr> <td align="left" styleCode="Toprule Lrule Rrule " valign="bottom">SGPT/ALT &gt;5 x ULN at 2 postbaseline visits</td> <td align="center" styleCode="Toprule Lrule Rrule ">25 (8) </td> <td align="center" styleCode="Toprule Lrule Rrule ">7 (2) </td> <td align="center" styleCode="Toprule Lrule Rrule ">2 (2)</td> <td align="center" styleCode="Toprule Lrule Rrule ">0</td> <td align="center" styleCode="Toprule Lrule Rrule ">9 (1)</td> </tr> <tr> <td align="left" styleCode="Toprule Lrule Rrule " valign="bottom">SGPT/ALT &gt;5 x ULN at 2 consecutive postbaseline visits</td> <td align="center" styleCode="Toprule Lrule Rrule ">17 (6)</td> <td align="center" styleCode="Toprule Lrule Rrule ">5 (2)</td> <td align="center" styleCode="Toprule Lrule Rrule ">5 (4)</td> <td align="center" styleCode="Toprule Lrule Rrule ">0</td> <td align="center" styleCode="Toprule Lrule Rrule ">5 (1)</td> </tr> </tbody> </table>

<table> <caption>Table 3. Adverse Reactions Occurring in &gt;5% in NTDT Patients</caption> <col width="200"/> <col width="130"/> <col width="130"/> <col width="130"/> <tbody> <tr> <td styleCode="Toprule Lrule "/> <td colspan="2" align="center" styleCode="Toprule Rrule Lrule "> <content styleCode="bold">Study 4</content> </td> <td align="center" styleCode="Toprule Rrule Lrule "> <content styleCode="bold">Study 5</content> </td> </tr> <tr> <td styleCode="Lrule Rrule "/> <td align="center" styleCode="Toprule "> <content styleCode="bold">Deferasirox</content> </td> <td align="center" styleCode="Toprule Rrule "> <content styleCode="bold">Placebo</content> </td> <td align="center" styleCode="Toprule Rrule "> <content styleCode="bold">Deferasirox</content> </td> </tr> <tr> <td styleCode="Lrule Rrule "/> <td align="center"> <content styleCode="bold">N=110</content> </td> <td align="center" styleCode="Rrule "> <content styleCode="bold">N=56</content> </td> <td align="center" styleCode="Rrule "> <content styleCode="bold">N=130</content> </td> </tr> <tr> <td styleCode="Lrule "/> <td align="center" styleCode="Lrule "> <content styleCode="bold">n (%)</content> </td> <td align="center" styleCode="Rrule "> <content styleCode="bold">n (%)</content> </td> <td align="center" styleCode="Rrule "> <content styleCode="bold">n (%)</content> </td> </tr> <tr> <td styleCode="Toprule Rrule Lrule "> <content styleCode="bold">Any adverse reaction</content> </td> <td align="center" styleCode="Toprule "> <content styleCode="bold">31 (28)</content> </td> <td align="center" styleCode="Toprule Rrule "> <content styleCode="bold">9 (16)</content> </td> <td align="center" styleCode="Toprule Rrule "> <content styleCode="bold">27 (21)</content> </td> </tr> <tr> <td styleCode="Rrule Lrule ">Nausea</td> <td align="center">7 (6)</td> <td align="center" styleCode="Rrule ">4 (7)</td> <td align="center" styleCode="Rrule ">2 (2)</td> </tr> <tr> <td styleCode="Rrule Lrule ">Rash</td> <td align="center">7 (6)</td> <td align="center" styleCode="Rrule ">1 (2)</td> <td align="center" styleCode="Rrule ">2 (2)</td> </tr> <tr> <td styleCode="Rrule Lrule ">Diarrhea</td> <td align="center">5 (5)</td> <td align="center" styleCode="Rrule ">1 (2)</td> <td align="center" styleCode="Rrule ">7 (5)</td> </tr> </tbody> </table>