JADENU (deferasirox) is an iron-chelating agent provided as a tablet or granules for oral use. Deferasirox is designated chemically as 4-[3,5-bis(2-hydroxyphenyl)-1 H -1,2,4-triazol-1-yl]benzoic acid and has the following structural formula: Deferasirox is a white to slightly yellow powder. It has a molecular formula C 21 H 15 N 3 O 4 and molecular weight of 373.4 g/mol. It is insoluble in water with a pH of suspension of 4.1. JADENU tablets contain 90 mg, 180 mg, or 360 mg deferasirox. Inactive ingredients include colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose, poloxamer (188), and povidone (K30). The film coating contains opadry blue. JADENU Sprinkle granules contain 90 mg, 180 mg, or 360 mg deferasirox. Inactive ingredients include colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose, povidone (K30), poloxamer (188). Deferasirox structural formula.

JADENU is an iron chelator indicated for the treatment of chronic iron overload due to blood transfusions in patients 2 years of age and older. JADENU is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes, and with a liver iron (Fe) concentration (LIC) of at least 5 mg Fe per gram of dry weight (Fe/g dw) and a serum ferritin greater than 300 mcg/L. Limitations of Use: The safety and efficacy of JADENU when administered with other iron chelation therapy have not been established

Treatment of Chronic Iron Overload Due to Blood Transfusions (Transfusional Iron Overload) JADENU is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older

Treatment of Chronic Iron Overload in Non-Transfusion-Dependent Thalassemia Syndromes JADENU is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes and with a liver iron concentration (LIC) of at least 5 milligrams of iron per gram of liver dry weight (mg Fe/g dw) and a serum ferritin greater than 300 mcg/L

Limitations of Use The safety and efficacy of JADENU when administered with other iron chelation therapy have not been established.

90 mg JADENU tablets Light blue oval biconvex film-coated tablet with beveled edges, debossed with “NVR” on one side and ‘90’ on a slight upward slope in between two debossed curved lines on the other side. 180 mg JADENU tablets Medium blue oval biconvex film-coated tablet with beveled edges, debossed with “NVR” on one side and ‘180’ on a slight upward slope in between two debossed curved lines on the other side. 360 mg JADENU tablets Dark blue oval biconvex film-coated tablet with beveled edges, debossed with “NVR” on one side and ‘360’ on a slight upward slope in between two debossed curved lines on the other side. 90 mg JADENU Sprinkle granules Supplied in cartons containing 30 child resistant foil sachets. Each sachet contains 162 mg of white to almost white granules, equivalent to 90 mg deferasirox. 180 mg JADENU Sprinkle granules Supplied in cartons containing 30 child resistant foil sachets. Each sachet contains 324 mg of white to almost white granules, equivalent to 180 mg deferasirox. 360 mg JADENU Sprinkle granules Supplied in cartons containing 30 child resistant foil sachets. Each sachet contains 648 mg of white to almost white granules, equivalent to 360 mg deferasirox. Tablets: 90 mg, 180 mg, 360 mg. Granules: 90 mg, 180 mg, 360 mg.

Transfusional Iron Overload: Initial dose for patients with estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m 2 is 14 mg per kg (calculated to nearest whole tablet or nearest whole sachet content for granules) once daily. NTDT Syndromes: Initial dose for patients with eGFR greater than 60 mL/min/1.73 m 2 is 7 mg per kg (calculated to nearest whole tablet or nearest whole sachet content for granules) once daily. See full prescribing information for information regarding monitoring, administration, and dose-reductions for organ impairment. ( 2.1 , 2.2 , 2.3 , 2.4 ) 2.1 Transfusional Iron Overload JADENU therapy should only be considered when a patient has evidence of chronic transfusional iron overload. The evidence should include the transfusion of at least 100 mL/kg of packed red blood cells (e.g., at least 20 units of packed red blood cells for a 40 kg person or more in individuals weighing more than 40 kg), and a serum ferritin consistently greater than 1,000 mcg/L. Prior to starting therapy, or increasing dose, evaluate: Serum ferritin level Baseline renal function: Obtain serum creatinine in duplicate (due to variations in measurements). Calculate the estimated glomerular filtration rate (eGFR). Use a prediction equation appropriate for adult patients (e.g., CKD-EPI, MDRD method) and in pediatric patients (e.g., Schwartz equations). Obtain urinalyses and serum electrolytes to evaluate renal tubular function . Serum transaminases and bilirubin Baseline auditory and ophthalmic examinations Initiating Therapy: The recommended initial dose of JADENU for patients 2 years of age and older with eGFR greater than 60 mL/min/1.73 m 2 is 14 mg per kg body weight orally, once daily. Calculate doses (mg per kg per day) to the nearest whole tablet or nearest whole sachet content for granules. Changes in weight of pediatric patients over time must be taken into account when calculating the dose. During Therapy: Monitor serum ferritin monthly and adjust the dose of JADENU, if necessary, every 3 to 6 months based on serum ferritin trends. Use the minimum effective dose to achieve a trend of decreasing ferritin. Make dose adjustments in steps of 3.5 or 7 mg per kg and tailor adjustments to the individual patient’s response and therapeutic goals. In patients not adequately controlled with doses of 21 mg per kg (e.g., serum ferritin levels persistently above 2,500 mcg/L and not showing a decreasing trend over time), doses of up to 28 mg per kg may be considered. Doses above 28 mg per kg are not recommended . Adjust dose based on serum ferritin levels If the serum ferritin falls below 1,000 mcg/L at 2 consecutive visits, consider dose reduction especially if the JADENU dose is greater than 17.5 mg/kg/day . If the serum ferritin falls below 500 mcg/L, interrupt JADENU therapy to minimize the risk of overchelation, and continue monthly monitoring . Evaluate the need for ongoing chelation therapy for patients whose conditions no longer require regular blood transfusions. Use the minimum effective dose to maintain iron burden in the target range . Monitor blood counts, liver function, renal function and ferritin monthly . Interrupt JADENU for pediatric patients who have acute illnesses, which can cause volume depletion, such as vomiting, diarrhea, or prolonged decreased oral intake, and monitor more frequently. Resume therapy as appropriate, based on assessments of renal function, when oral intake and volume status are normal

Iron Overload in Non-Transfusion-Dependent Thalassemia Syndromes JADENU therapy should only be considered when a patient with NTDT syndrome has an LIC of at least 5 mg Fe/g dw and a serum ferritin greater than 300 mcg/L. Prior to starting therapy, obtain: LIC by liver biopsy or by an FDA-cleared or approved method for identifying patients for treatment with deferasirox therapy Serum ferritin level on at least 2 measurements 1-month apart Baseline renal function: Obtain serum creatinine in duplicate (due to variations in measurements). Calculate the estimated glomerular filtration rate (eGFR). Use a prediction equation appropriate for adult patients (e.g., CKD-EPI, MDRD method) and in pediatric patients (e.g., Schwartz equations). Obtain urinalyses and serum electrolytes to evaluate renal tubular function . Serum transaminases and bilirubin Baseline auditory and ophthalmic examinations Initiating Therapy: The recommended initial dose of JADENU for patients with eGFR greater than 60 mL/min/1.73 m 2 is 7 mg per kg body weight orally once daily. Calculate doses (mg per kg per day) to the nearest whole tablet or nearest whole sachet content for granules. If the baseline LIC is greater than 15 mg Fe/g dw, consider increasing the dose to 14 mg/kg/day after 4 weeks. During Therapy: Monitor serum ferritin monthly to assess the patient’s response to therapy and to minimize the risk of overchelation . Interrupt treatment when serum ferritin is less than 300 mcg/L and obtain an LIC to determine whether the LIC has fallen to less than 3 mg Fe/g dw. Use the minimum effective dose to achieve a trend of decreasing ferritin. Monitor LIC every 6 months. After 6 months of therapy, if the LIC remains greater than 7 mg Fe/g dw, increase the dose of deferasirox to a maximum of 14 mg/kg/day. Do not exceed a maximum of 14 mg/kg/day. If after 6 months of therapy, the LIC is 3 to 7 mg Fe/g dw, continue treatment with deferasirox at no more than 7 mg/kg/day. When the LIC is less than 3 mg Fe/g dw, interrupt treatment with deferasirox and continue to monitor the LIC. Monitor blood counts, liver function, renal function and ferritin monthly . Increase monitoring frequency for pediatric patients who have acute illness, which can cause volume depletion, such as vomiting, diarrhea, or prolonged decreased oral intake. Consider dose interruption until oral intake and volume status are normal . Restart treatment when the LIC rises again to more than 5 mg Fe/g dw

Administration Swallow JADENU tablets once daily with water or other liquids, preferably at the same time each day. Take JADENU tablets on an empty stomach or with a light meal (contains less than 7% fat content and approximately 250 calories). Examples of light meals include 1 whole wheat English muffin, 1 packet jelly (0.5 ounces), and skim milk (8 fluid ounces) or a turkey sandwich (2 oz. turkey on whole wheat bread w/ lettuce, tomato, and 1 packet mustard). Do not take JADENU tablets with aluminum-containing antacid products . For patients who have difficulty swallowing whole tablets, JADENU tablets may be crushed and mixed with soft foods (e.g., yogurt or applesauce) immediately prior to use and administered orally. Commercial crushers with serrated surfaces should be avoided for crushing a single 90 mg tablet. The dose should be immediately and completely consumed and not stored for future use. Take JADENU Sprinkle granules on an empty stomach or with a light meal . Administer JADENU Sprinkle granules by sprinkling the full dose on soft food (e.g., yogurt or applesauce) immediately prior to use and administered orally. JADENU Sprinkle granules should be taken once a day, preferably at the same time each day. Do not take JADENU Sprinkle granules with aluminum-containing antacid products . For patients who are currently on chelation therapy with Exjade tablets for oral suspension and converting to JADENU, the dose should be about 30% lower, rounded to the nearest whole tablet or nearest whole sachet content for granules. The table below provides additional information on dosing conversion to JADENU. EXJADE Tablets for oral suspension (white round tablet) JADENU Tablets (film coated blue oval tablet) JADENU Sprinkle Granules (white to almost white granules) Transfusion-Dependent Iron Overload Starting Dose 20 mg/kg/day 14 mg/kg/day Titration Increments 5–10 mg/kg 3.5–7 mg/kg Maximum Dose 40 mg/kg/day 28 mg/kg/day Non-Transfusion-Dependent Thalassemia Syndromes Starting Dose 10 mg/kg/day 7 mg/kg/day Titration Increments 5–10 mg/kg 3.5–7 mg/kg Maximum Dose 20 mg/kg/day 14 mg/kg/day 2.4 Use in Patients With Baseline Hepatic or Renal Impairment Patients with Baseline Hepatic Impairment Mild (Child-Pugh A) Hepatic Impairment: No dose adjustment is necessary. Moderate (Child-Pugh B) Hepatic Impairment: Reduce the starting dose by 50%. Severe (Child-Pugh C) Hepatic Impairment: Avoid JADENU tablets or JADENU Sprinkle granules . Patients with Baseline Renal Impairment Do not use JADENU in adult or pediatric patients with eGFR less than 40 mL/min/1.73 m 2 . For patients with renal impairment (eGFR 40-60 mL/min/1.73 m 2 ), reduce the starting dose by 50% . Exercise caution in pediatric patients with eGFR between 40 and 60 mL/minute/1.73 m 2 . If treatment is needed, use the minimum effective dose and monitor renal function frequently. Individualize dose titration based on improvement in renal injury

Dose Modifications for Decreases in Renal Function While on JADENU JADENU is contraindicated in patients with eGFR less than 40 mL/min/1.73 m 2 . For decreases in renal function while receiving JADENU , modify the dose as follows: Transfusional Iron Overload Adults: If the serum creatinine increases by 33% or more above the average baseline measurement, repeat the serum creatinine within 1 week, and if still elevated by 33% or more, reduce the dose by 7 mg per kg. Pediatric Patients (ages 2 years–17 years): Reduce the dose by 7 mg per kg if eGFR decreases by greater than 33% below the average baseline measurement and repeat eGFR within 1 week. Interrupt JADENU for acute illnesses, which can cause volume depletion, such as vomiting, diarrhea, or prolonged decreased oral intake, and monitor more frequently. Resume therapy as appropriate, based on assessments of renal function, when oral intake and volume status are normal. Avoid use of other nephrotoxic drugs . In the setting of decreased renal function, evaluate the risk benefit profile of continued JADENU use. Use the minimum effective JADENU dose and monitor renal function more frequently, by evaluating tubular and glomerular function. Titrate dosing based on renal injury. Consider dose reduction or interruption and less nephrotoxic therapies until improvement of renal function. If signs of renal tubular or glomerular injury occur in the presence of other risk factors such as volume depletion, reduce or interrupt JADENU to prevent severe and irreversible renal injury . All Patients (regardless of age): Discontinue therapy for eGFR less than 40 mL/min/1.73 m 2 . Non-Transfusion-Dependent Thalassemia Syndromes Adults: If the serum creatinine increases by 33% or more above the average baseline measurement, repeat the serum creatinine within 1 week, and if still elevated by 33% or more, interrupt therapy if the dose is 3.5 mg per kg, or reduce by 50% if the dose is 7 or 14 mg per kg. Pediatric Patients (ages 10 years–17 years): Reduce the dose by 3.5 mg per kg if eGFR decreases by greater than 33% below the average baseline measurement and repeat the eGFR within 1 week. Increase monitoring frequency for pediatric patients who have acute illnesses, which can cause volume depletion, such as vomiting, diarrhea, or prolonged decreased oral intake. Consider dose interruption until oral intake and volume status are normal. Avoid use of other nephrotoxic drugs . In the setting of decreased renal function, evaluate the risk benefit profile of continued JADENU use. Use the minimum effective JADENU dose and monitor renal function more frequently, by evaluating tubular and glomerular function. Titrate dosing based on renal injury. Consider dose reduction or interruption and less nephrotoxic therapies until improvement of renal function. If signs of renal tubular or glomerular injury occur in the presence of other risk factors such as volume depletion, reduce or interrupt JADENU to prevent severe and irreversible renal injury . All Patients (regardless of age): Discontinue therapy for eGFR less than 40 mL/min/1.73 m 2

Dose Modifications Based on Concomitant Medications UDP-glucuronosyltransferases (UGT) Inducers Concomitant use of UGT inducers decreases systemic exposure. Avoid the concomitant use of strong UGT inducers (e.g., rifampicin, phenytoin, phenobarbital, ritonavir). If you must administer JADENU tablets or JADENU Sprinkle granules with a strong UGT inducer, consider increasing the initial dose by 50%, and monitor serum ferritin levels and clinical responses for further dose modification . Bile Acid Sequestrants Concomitant use of bile acid sequestrants decreases systemic exposure. Avoid the concomitant use of bile acid sequestrants (e.g., cholestyramine, colesevelam, colestipol). If you must administer JADENU tablets or JADENU Sprinkle granules with a bile acid sequestrant, consider increasing the initial dose by 50%, and monitor serum ferritin levels and clinical responses for further dose modification .

Acute Kidney Injury: Measure serum creatinine in duplicate before starting therapy. Monitor renal function during JADENU therapy and reduce dose or interrupt therapy for toxicity. ( 2.1 , 2.4 , 5.1 ) Hepatic Toxicity: Monitor hepatic function. Reduce dose or interrupt therapy for toxicity. Fatal and Nonfatal Gastrointestinal (GI) Bleeding, Ulceration, and Irritation: Risk may be greater in patients who are taking JADENU in combination with drugs that have known ulcerogenic or hemorrhagic potential. Bone Marrow Suppression: Neutropenia, agranulocytosis, worsening anemia, and thrombocytopenia, including fatal events; monitor blood counts during JADENU therapy. Interrupt therapy for toxicity. Age-related Risk of Toxicity: Monitor elderly and pediatric patients closely for toxicity. Hypersensitivity Reactions: Discontinue JADENU for severe reactions and institute medical intervention. Severe Skin Reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS): Discontinue JADENU. 5.1 Acute Kidney Injury, Including Acute Renal Failure Requiring Dialysis and Renal Tubular Toxicity Including Fanconi Syndrome JADENU is contraindicated in patients with eGFR less than 40 mL/min/1.73 m 2 . Exercise caution in pediatric patients with eGFR between 40 and 60 mL/min/1.73 m 2 . If treatment is needed, use the minimum effective dose and monitor renal function frequently. Individualize dose titration based on improvement in renal injury . For patients with renal impairment (eGFR 40-60 mL/min/1.73 m 2 ) reduce the starting dose by 50% . JADENU can cause acute kidney injury including renal failure requiring dialysis that has resulted in fatal outcomes. Based on postmarketing experience, most fatalities have occurred in patients with multiple comorbidities and who were in advanced stages of their hematological disorders. In the clinical trials, adults and pediatric deferasirox-treated patients with no preexisting renal disease experienced dose-dependent mild, non-progressive increases in serum creatinine and proteinuria. Preexisting renal disease and concomitant use of other nephrotoxic drugs may increase the risk of acute kidney injury in adult and pediatric patients. Acute illnesses associated with volume depletion and overchelation may increase the risk of acute kidney injury in pediatric patients. In pediatric patients, small decreases in eGFR can result in increases in deferasirox exposure, particularly in younger patients with body surface area typical of patients less than age 7 years. This can lead to a cycle of worsening renal function and further increases in Exjade exposure, unless the dose is reduced or interrupted. Renal tubular toxicity, including acquired Fanconi syndrome, has been reported in patients treated with deferasirox, most commonly in pediatric patients with beta-thalassemia and serum ferritin levels less than 1,500 mcg/L . Evaluate renal glomerular and tubular function before initiating therapy or increasing the dose. Use prediction equations validated for use in adult and pediatric patients to estimate GFR. Obtain serum electrolytes and urinalysis in all patients to evaluate renal tubular function . Monitor all patients for changes in eGFR and for renal tubular toxicity weekly during the first month after initiation or modification of therapy and at least monthly thereafter. Dose reduction or interruption may be considered if abnormalities occur in levels of markers of renal tubular function and/or as clinically indicated. Monitor serum ferritin monthly to evaluate for overchelation. Use the minimum dose to establish and maintain a low iron burden. Monitor renal function more frequently in patients with preexisting renal disease or decreased renal function. In pediatric patients, interrupt JADENU during acute illnesses, which can cause volume depletion such as vomiting, diarrhea, or prolonged decreased oral intake, and monitor renal function more frequently. Promptly correct fluid deficits to prevent renal injury. Resume therapy as appropriate, based on assessments of renal function, when oral intake and volume status are normal

Hepatic Toxicity and Failure JADENU 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 . Acute liver injury and failure, including fatal outcomes, have occurred in pediatric deferasirox-treated patients. Liver failure occurred in association with acute kidney injury in pediatric patients at risk for overchelation during a volume-depleting event. Interrupt JADENU therapy when acute liver injury or acute kidney injury is suspected and during volume depletion. Monitor liver and renal function more frequently in pediatric patients who are receiving JADENU in the 14-28 mg/kg/day range and when iron burden is approaching normal. Use the minimum effective dose to achieve and maintain a low iron burden . Measure transaminases [aspartate transaminase (AST) and alanine transaminase (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 . Patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment may be at higher risk for hepatic toxicity

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 . 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 reaction is suspected. The risk of GI 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 GI perforation (including fatal outcome)

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

Age-Related Risk of Toxicity Elderly Patients JADENU has been associated with serious and fatal adverse reactions in the postmarketing setting among adults, predominantly in elderly patients. Monitor elderly patients treated with JADENU more frequently for toxicity . Pediatric Patients JADENU has been associated with serious and fatal adverse reactions in pediatric patients in the postmarketing setting. These events were frequently associated with volume depletion or with continued Exjade doses in the 20-40 mg/kg/day range equivalent to 14-28 mg/kg/day JADENU when body iron burden was approaching or in the normal range. Interrupt JADENU in patients with volume depletion, and resume JADENU when renal function and fluid volume have normalized. Monitor liver and renal function more frequently during volume depletion and in patients receiving JADENU in the 14-28 mg/kg/day range when iron burden is approaching the normal range. Use the minimum effective dose to achieve and maintain a low iron burden

Overchelation For patients with transfusional iron overload, measure serum ferritin monthly to assess the patient’s response to therapy and minimize the risk of overchelation. An analysis of pediatric patients treated with Exjade in pooled clinical trials (n = 158), found a higher rate of renal adverse reactions among patients receiving doses greater than 25 mg/kg/day equivalent to 17.5 mg/kg/day JADENU while their serum ferritin values were less than 1,000 mcg/L. Consider dose reduction or closer monitoring of renal and hepatic function, and serum ferritin levels during these periods. Use the minimum effective dose to maintain a low-iron burden . If the serum ferritin falls below 1,000 mcg/L at 2 consecutive visits, consider dose reduction, especially if the JADENU dose is greater than 17.5 mg/kg/day . If the serum ferritin falls below 500 mcg/L, interrupt therapy with JADENU and continue monthly monitoring. Evaluate the need for ongoing chelation for patients whose conditions do not require regular blood transfusions. Use the minimum effective dose to maintain iron burden in the target range. Continued administration of JADENU in the 14 to 28 mg/kg/day range, when the body iron burden is approaching or within the normal range can result in life-threatening adverse reactions . 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

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 . 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

Severe Skin Reactions Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) which could be life-threatening or fatal have been reported during deferasirox therapy . Cases of erythema multiforme have been observed. Advise patients of the signs and symptoms of severe skin reactions, and closely monitor. If any severe skin reactions are suspected, discontinue JADENU immediately and do not reintroduce JADENU therapy

Skin Rash Rashes may occur during JADENU treatment . 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

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. The frequency of auditory adverse reactions was increased among pediatric patients, who received Exjade doses greater than 25 mg/kg/day equivalent to 17.5 mg/kg/day JADENU when serum ferritin was less than 1,000 mcg/L . 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.

Do not take JADENU with aluminum-containing antacid preparations. Deferasirox increases the exposure of repaglinide. Consider repaglinide dose reduction and monitor blood glucose levels. Avoid the use of JADENU with theophylline as theophylline levels could be increased. Deferasirox increases exposure of busulfan. Monitor plasma concentrations of busulfan when coadministered with deferasirox to allow dose adjustment of busulfan, as needed

Aluminum-Containing Antacid Preparations The concomitant administration of JADENU and aluminum-containing antacid preparations has not been formally studied. Although deferasirox has a lower affinity for aluminum than for iron, do not take JADENU with aluminum-containing antacid preparations

Agents Metabolized by CYP3A4 Deferasirox may induce CYP3A4 resulting in a decrease in CYP3A4 substrate concentration when these drugs are coadministered. Closely monitor patients for signs of reduced effectiveness when deferasirox is administered with drugs metabolized by CYP3A4 (e.g., alfentanil, aprepitant, budesonide, buspirone, conivaptan, cyclosporine, darifenacin, darunavir, dasatinib, dihydroergotamine, dronedarone, eletriptan, eplerenone, ergotamine, everolimus, felodipine, fentanyl, hormonal contraceptive agents, indinavir, fluticasone, lopinavir, lovastatin, lurasidone, maraviroc, midazolam, nisoldipine, pimozide, quetiapine, quinidine, saquinavir, sildenafil, simvastatin, sirolimus, tacrolimus, tolvaptan, tipranavir, triazolam, ticagrelor, and vardenafil)

Agents Metabolized by CYP2C8 Deferasirox inhibits CYP2C8 resulting in an increase in CYP2C8 substrate (e.g., repaglinide and paclitaxel) concentration when these drugs are coadministered. If JADENU and repaglinide are used concomitantly, consider decreasing the dose of repaglinide and perform careful monitoring of blood glucose levels. Closely monitor patients for signs of exposure related toxicity when JADENU is coadministered with other CYP2C8 substrates

Agents Metabolized by CYP1A2 Deferasirox inhibits CYP1A2 resulting in an increase in CYP1A2 substrate (e.g., alosetron, caffeine, duloxetine, melatonin, ramelteon, tacrine, theophylline, tizanidine) concentration when these drugs are coadministered. An increase in theophylline plasma concentrations could lead to clinically significant theophylline induced CNS or other adverse reactions. Avoid the concomitant use of theophylline or other CYP1A2 substrates with a narrow therapeutic index (e.g., tizanidine) with JADENU. Monitor theophylline concentrations and consider theophylline dose modification if you must coadminister theophylline with JADENU. Closely monitor patients for signs of exposure related toxicity when JADENU is coadministered with other drugs metabolized by CYP1A2

Agents Inducing UDP-glucuronosyltransferase (UGT) Metabolism Deferasirox is a substrate of UGT1A1 and to a lesser extent UGT1A3. The concomitant use of JADENU with strong UGT inducers (e.g., rifampicin, phenytoin, phenobarbital, ritonavir) may result in a decrease in JADENU efficacy due to a possible decrease in deferasirox concentration. Avoid the concomitant use of strong UGT inducers with JADENU. Consider increasing the initial dose of JADENU if you must coadminister these agents together

Bile Acid Sequestrants Avoid the concomitant use of bile acid sequestrants (e.g., cholestyramine, colesevelam, colestipol) with JADENU due to a possible decrease in deferasirox concentration. If you must coadminister these agents together, consider increasing the initial dose of JADENU

Busulfan Increased exposure of busulfan was observed with concomitant use with deferasirox. Monitor plasma concentrations of busulfan when coadministered with deferasirox to allow dose adjustment of busulfan as needed .