Prescription Drug Information: Deferasirox

DEFERASIROX — deferasirox tablet
MSN LABORATORIES PRIVATE LIMITED

WARNING: RENAL FAILURE, HEPATIC FAILURE, and GASTROINTESTINAL HEMORRHAGE

Renal Failure

  • Deferasirox 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 deferasirox dosing in all patients. Deferasirox 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)].

Hepatic Failure

  • Deferasirox 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 deferasirox 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

  • Deferasirox 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 deferasirox for suspected GI ulceration or hemorrhage [see Warnings and Precautions (5.3)].

1 INDICATIONS AND USAGE

1.1 Treatment of Chronic Iron Overload Due to Blood Transfusions (Transfusional Iron Overload)

Deferasirox tablets are indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older.

1.2 Treatment of Chronic Iron Overload in Non-Transfusion-Dependent Thalassemia Syndromes

Deferasirox tablets are 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.

1.3 Limitations of Use

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

2 DOSAGE AND ADMINISTRATION

2.1Transfusional Iron Overload

Deferasirox tablets 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:

Initiating Therapy:
The recommended initial dose of deferasirox tablets for patients 2 years of age and older with eGFR greater than 60 mL/min/1.73 m2 is 14 mg per kg body weight orally, once daily. Calculate doses (mg per kg per day) to the nearest whole tablet. 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 deferasirox tablets, 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 deferasirox tablets dose is greater than 17.5 mg/kg/day [see Adverse Reactions (6.1)].
    • If the serum ferritin falls below 500 mcg/L, interrupt deferasirox tablets 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 deferasirox tablets 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

Deferasirox tablets 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 deferasirox tablets for patients with eGFR greater than 60 mL/min/1.73 m2 is 7 mg per kg body weight orally once daily. Calculate doses (mg per kg per day) to the nearest whole tablet.
  • 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.

2.3Administration

Swallow deferasirox tablets once daily with water or other liquids, preferably at the same time each day. Take deferasirox 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 deferasirox tablets with aluminum-containing antacid products [see Drug Interactions (7.1)]. For patients who have difficulty swallowing whole tablets, deferasirox 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.
For patients who are currently on chelation therapy with deferasirox tablets for oral suspension and converting to deferasirox tablets, the dose should be about 30% lower, rounded to the nearest whole tablet.The table below provides additional information on dosing conversion to deferasirox tablets.

Deferasirox Tablets for oral suspension (white round tablet) Deferasirox Tablets (film coated yellow oval tablet)
Transfusion-Dependent Iron Overload
Starting Dose 20 mg/kg/day 14 mg/kg/day
Titration Increments 5 to 10 mg/kg 3.5 to 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 to 10 mg/kg 3.5 to 7 mg/kg
Maximum Dose 20 mg/kg/day 14 mg/kg/day

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