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

Exjade is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. This indication is based on a reduction of liver iron concentrations and serum ferritin levels [see Clinical Studies]. An improvement in survival or disease related symptoms has not been established.

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

Exjade is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion dependent thalassemia 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. This indication is based on achievement of an LIC less than 5 mg Fe/g dw [see Clinical Studies]. An improvement in survival or disease-related symptoms has not been established.

Limitation of Use

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

Transfusional iron overload

Exjade 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 1000 mcg/L.

Prior to starting therapy, obtain:

• serum ferritin level
• baseline serum creatinine in duplicate (due to variations in measurements) and determine the creatinine clearance (Cockcroft-Gault method) [see WARNINGS AND PRECAUTIONS]
• serum transaminases and bilirubin [see WARNINGS AND PRECAUTIONS]
• baseline auditory and ophthalmic examinations [see WARNINGS AND PRECAUTIONS]

The recommended initial dose of Exjade for patients 2 years of age and older is 20 mg per kg body weight orally, once daily. Calculate doses (mg per kg per day) to the nearest whole tablet.

After commencing therapy, monitor serum ferritin monthly and adjust the dose of Exjade, if necessary, every 3-6 months based on serum ferritin trends. Make dose adjustments in steps of 5 or 10 mg per kg and tailor adjustments to the individual patient's response and therapeutic goals. In patients not adequately controlled with doses of 30 mg per kg (e.g., serum ferritin levels persistently above 2500 mcg/L and not showing a decreasing trend over time), doses of up to 40 mg per kg may be considered. Doses above 40 mg per kg are not recommended.

If the serum ferritin falls consistently below 500 mcg/L, consider temporarily interrupting therapy with Exjade [see WARNINGS AND PRECAUTIONS].

Iron overload in Non-transfusion dependent thalassemia syndromes

Exjade therapy should only be considered when a patient with a non-transfusion dependent thalassemia 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 one month apart [see Clinical Studies]
• Baseline serum creatinine in duplicate (due to variations in measurements) and determine the creatinine clearance (Cockcroft-Gault method) [see WARNINGS AND PRECAUTIONS]
• Serum transaminases and bilirubin [see WARNINGS AND PRECAUTIONS]
• Baseline auditory and ophthalmic examinations [see WARNINGS AND PRECAUTIONS]

Initiating therapy:

• The recommended initial dose of Exjade is 10 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 20 mg/kg/day after 4 weeks.

During therapy:

• Monitor serum ferritin monthly. 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.
• 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 20 mg/kg/day. Do not exceed a maximum of 20 mg/kg/day.
• If after 6 months of therapy, the LIC is 3-7 mg Fe/g dw, continue treatment with deferasirox at no more than 10 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, hepatic function, and renal function [see WARNINGS AND PRECAUTIONS].

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

Administration

Do not chew tablets or swallow them whole.

Take Exjade once daily on an empty stomach at least 30 minutes before food, preferably at the same time each day. Completely disperse tablets by stirring in water, orange juice, or apple juice until a fine suspension is obtained. Disperse doses of less than 1 g in 3.5 ounces of liquid and doses of 1 g or greater in 7 ounces of liquid. After swallowing the suspension, re-suspend any residue in a small volume of liquid and swallow. Do not take Exjade with aluminum-containing antacid products [see DRUG INTERACTIONS].

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 Exjade [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].

Patients with Baseline Renal Impairment

For patients with a baseline serum creatinine less than 2 times the age appropriate upper limit of normal, initial dosing is the same as described for patients with a normal creatinine. Do not use Exjade in patients with serum creatinine greater than 2 times the upper limit of normal [see CONTRAINDICATIONS].

Dose Modifications for Increases in Serum Creatinine on Exjade

For serum creatinine increases while receiving Exjade [see WARNINGS AND PRECAUTIONS] modify the dose as follows:

Transfusional iron overload

Adults and adolescents (ages 16 and older):

• If the serum creatinine increases by 33% or more above the average baseline measurement, repeat the serum creatinine within one week, and if still elevated by 33% or more, reduce the dose by 10 mg per kg.

Pediatric Patients (ages 2-15 years):

• Reduce the dose by 10 mg per kg if serum creatinine increases to greater than 33% above the average baseline measurement and greater than the age appropriate upper limit of normal.

All Patients (regardless of age):

• Discontinue therapy for serum creatinine greater than 2 times the age-appropriate upper limit of normal or for creatinine clearance < 40 mL/min. [see CONTRAINDICATIONS]

Non-transfusion dependent thalassemia syndromes

Adults and adolescents (ages 16 and older):

• If the serum creatinine increases by 33% or more above the average baseline measurement, repeat the serum creatinine within one week, and if still elevated by 33% or more, interrupt therapy if the dose is 5 mg per kg, or reduce by 50% if the dose is 10 or 20 mg per kg.

Pediatric Patients (ages 10-15 years):

• Reduce the dose by 5 mg per kg if serum creatinine increases to greater than 33% above the average baseline measurement and greater than the age appropriate upper limit of normal.

All Patients (regardless of age):

• Discontinue therapy for serum creatinine greater than 2 times the age-appropriate upper limit of normal or for creatinine clearance < 40 mL/min [see CONTRAINDICATIONS].

Dose Modifications Based on Concomitant Medications

UDP-glucuronosyltransferases (UGT) inducers

Concomitant use of UGT inducers decreases Exjade systemic exposure. Avoid the concomitant use of potent UGT inducers (e.g., rifampicin, phenytoin, phenobarbital, ritonavir) with Exjade. If you must administer Exjade with one of these agents, consider increasing the initial dose of Exjade by 50%, and monitor serum ferritin levels and clinical responses for further dose modification [see DRUG INTERACTIONS].

Bile Acid Sequestrants

Concomitant use of bile acid sequestrants decreases Exjade systemic exposure. Avoid the concomitant use of bile acid sequestrants (e.g., cholestyramine, colesevelam, colestipol) with Exjade. If you must administer Exjade with one of these agents, consider increasing the initial dose of Exjade by 50%, and monitor serum ferritin levels and clinical responses for further dose modification [see DRUG INTERACTIONS].

Dosage Forms And Strengths

• 125 mg tablets
  Off-white, round, flat tablet with beveled edge and imprinted with “J” and “125” on one side and “NVR” on the other.
• 250 mg tablets
  Off-white, round, flat tablet with beveled edge and imprinted with “J” and “250” on one side and “NVR” on the other.
• 500 mg tablets
  Off-white, round, flat tablet with beveled edge and imprinted with “J” and “500” on one side and “NVR” on the other.

Storage And Handling

Exjade is provided as 125 mg, 250 mg, and 500 mg tablets for oral suspension.

125 mg

Off-white, round, flat tablet with beveled edge and imprinted with “J” and “125” on one side and “NVR” on the other.

Bottles of 30 tablets…………………………..(NDC 0078-0468-15)

250 mg

Off-white, round, flat tablet with beveled edge and imprinted with “J” and “250” on one side and “NVR” on the other.

Bottles of 30 tablets…………………………..(NDC 0078-0469-15)

500 mg

Off-white, round, flat tablet with beveled edge and imprinted with “J” and “500” on one side and “NVR” on the other.

Bottles of 30 tablets…………………………..(NDC 0078-0470-15)

Store Exjade tablets at 25°C (77°F); excursions are permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from moisture.

Manufactured by: Novartis Pharma Stein AG Stein, Switzerland Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936. Revised: 01/2013

Last reviewed on RxList: 2/5/2013
This monograph has been modified to include the generic and brand name in many instances.