Jadenu

• 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.
• Evaluate baseline renal function prior to starting or increasing JADENU dosing in all patients. JADENU is contraindicated in adult and pediatric patients with eGFR less than 40 mL/min/1.73 m². Measure serum creatinine in duplicate prior to initiation of therapy. Monitor renal function at least monthly. For patients with baseline renal impairment or increased risk of acute renal failure, monitor renal function weekly for the first month, then at least monthly. Reduce the starting dose in patients with preexisting renal disease. During therapy, increase the frequency of monitoring and modify the dose for patients with an increased risk of renal impairment, including use of concomitant nephrotoxic drugs, and pediatric patients with volume depletion or overchelation

  [see Dosage and Administration (2.1, 2.4, 2.5), Warnings and Precautions (5.1), Adverse Reactions (6.1, 6.2)]

  .

• 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)]

  .

• 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)]

  .

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. (

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

• Transfusional Iron Overload: Initial dose for patients with estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m² is 14 mg per kg (calculated to nearest whole tablet or nearest whole sachet content for granules) once daily. (
  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
      [see Dosage and Administration (2.4), Warnings and Precautions (5.1)]
      .
  • Serum transaminases and bilirubin
    [see Dosage and Administration (2.4), Warnings and Precautions (5.2)]
  • Baseline auditory and ophthalmic examinations
    [see Warnings and Precautions (5.10)]

  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 m²is 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
    [see Warnings and Precautions (5.6)]
    .
  • 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
      [see Adverse Reactions (6.1)]
      .
    • If the serum ferritin falls below 500 mcg/L, interrupt JADENU therapy to minimize the risk of overchelation, and continue monthly monitoring
      [see Warnings and Precautions (5.6)]
      .
    • 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
      [see Warnings and Precautions (5.6)]
      .
  • Monitor blood counts, liver function, renal function and ferritin monthly
    [see Warnings and Precautions (5.1, 5.2, 5.4)]
    .
  • 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
    [see Dosage and Administration (2.4, 2.5), Warnings and Precautions (5.1), Use in Specific Populations (8.4), Clinical Pharmacology (12.3)]
    .
  )
• NTDT Syndromes: Initial dose for patients with eGFR greater than 60 mL/min/1.73 m² is 7 mg per kg (calculated to nearest whole tablet or nearest whole sachet content for granules) once daily. (
  2.2     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
    [see Clinical Studies (14)]
  • 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
      [see Dosage and Administration (2.4), Warnings and Precautions (5.1)].
  • Serum transaminases and bilirubin
    [see Dosage and Administration (2.4), Warnings and Precautions (5.2)]
  • Baseline auditory and ophthalmic examinations
    [see Warnings and Precautions (5.10)]

  Initiating Therapy:

  • The recommended initial dose of JADENU for patients with eGFR greater than 60 mL/min/1.73 m²is 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
    [see Warnings and Precautions (5.6)]
    . 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
    [see Warnings and Precautions (5.1, 5.2, 5.4)]
    .
  • 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
    [see Dosage and Administration (2.4, 2.5), Warnings and Precautions (5.1), Use in Specific Populations (8.4), Clinical Pharmacology (12.3)]
    .

  Restart treatment when the LIC rises again to more than 5 mg Fe/g dw.
  )
• See full prescribing information for information regarding monitoring, administration, and dose-reductions for organ impairment. (
  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
      [see Dosage and Administration (2.4), Warnings and Precautions (5.1)]
      .
  • Serum transaminases and bilirubin
    [see Dosage and Administration (2.4), Warnings and Precautions (5.2)]
  • Baseline auditory and ophthalmic examinations
    [see Warnings and Precautions (5.10)]

  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 m²is 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
    [see Warnings and Precautions (5.6)]
    .
  • 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
      [see Adverse Reactions (6.1)]
      .
    • If the serum ferritin falls below 500 mcg/L, interrupt JADENU therapy to minimize the risk of overchelation, and continue monthly monitoring
      [see Warnings and Precautions (5.6)]
      .
    • 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
      [see Warnings and Precautions (5.6)]
      .
  • Monitor blood counts, liver function, renal function and ferritin monthly
    [see Warnings and Precautions (5.1, 5.2, 5.4)]
    .
  • 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
    [see Dosage and Administration (2.4, 2.5), Warnings and Precautions (5.1), Use in Specific Populations (8.4), Clinical Pharmacology (12.3)]
    .
  ,
  2.2     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
    [see Clinical Studies (14)]
  • 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
      [see Dosage and Administration (2.4), Warnings and Precautions (5.1)].
  • Serum transaminases and bilirubin
    [see Dosage and Administration (2.4), Warnings and Precautions (5.2)]
  • Baseline auditory and ophthalmic examinations
    [see Warnings and Precautions (5.10)]

  Initiating Therapy:

  • The recommended initial dose of JADENU for patients with eGFR greater than 60 mL/min/1.73 m²is 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
    [see Warnings and Precautions (5.6)]
    . 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
    [see Warnings and Precautions (5.1, 5.2, 5.4)]
    .
  • 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
    [see Dosage and Administration (2.4, 2.5), Warnings and Precautions (5.1), Use in Specific Populations (8.4), Clinical Pharmacology (12.3)]
    .

  Restart treatment when the LIC rises again to more than 5 mg Fe/g dw.
  ,
  2.3     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

  [see Drug Interactions (7.1)]

  . 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

  [see Clinical Pharmacology (12.3)]

  . 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

  [see Drug Interactions (7.1)]

  .

  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

  [see Warnings and Precautions (5.2), Use in Specific Populations (8.7)]

  .

  Patients with Baseline Renal Impairment

  Do not use JADENU in adult or pediatric patients with eGFR less than 40 mL/min/1.73 m²

  [see Dosage and Administration (2.5), Contraindications (4)]

  .

  For patients with renal impairment (eGFR 40-60 mL/min/1.73 m²), reduce the starting dose by 50%

  [see Use in Specific Populations (8.6)]

  .

  Exercise caution in pediatric patients with eGFR between 40 and 60 mL/minute/1.73 m². If treatment is needed, use the minimum effective dose and monitor renal function frequently. Individualize dose titration based on improvement in renal injury

  [see Use in Specific Populations (8.6)]

  .
  )

• 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.

Lactation: Advise women not to breastfeed. (