ical benefit and risks of Exjade therapy. In patients who are in need of iron chelation therapy, it is recommended that therapy with Exjade (deferasirox) be started when a patient has evidence of chronic iron overload, such as the transfusion of approximately 100mL/kg of packed red blood cells (approximately 20units for a 40-kg patient) and a serum ferritin consistently >1000mcg/L.
2.2 Dose Modifications
Exjade may require dose adjustment, interruption or cessation of the therapy due to toxicity or any of the following [see Warnings and Precautions (5.1-5.6), Geriatric Use (8.5)]:
Based on Serum Ferritin
After commencing initial therapy, monitor serum ferritin every month and adjust the dose of Exjade if necessary every 3-6months based on serum ferritin trends. Make dose adjustments in steps of 5 or 10mg/kg and tailor adjustments to the individual patient’s response and therapeutic goals (maintenance or reduction of body iron burden). In patients not adequately controlled with doses of 30mg/kg (e.g., serum ferritin levels persistently above 2500 mcg/L and not showing a decreasing trend over time), doses of up to 40mg/kg may be considered. Doses above 40mg/kg are not recommended.
If the serum ferritin falls consistently below 500mcg/L, consider temporarily interrupting therapy with Exjade.
Based on Serum Creatinine
For adults, reduce the daily dose of Exjade by 10mg/kg if a rise in serum creatinine to >33% above the average of the pretreatment measurements is seen at 2 consecutive visits, and cannot be attributed to other causes. For pediatric patients, reduce the dose by 10mg/kg if serum creatinine levels rise above the age-appropriate upper limit of normal at 2 consecutive visits.
Concomitant UGT inducers or Cholestyramine
Concomitant use of UGT inducers or cholestyramine decreases deferasirox systemic exposure (AUC). Avoid the concomitant use of cholestyramine or potent UGT inducers (e.g.,rifampicin, phenytoin, phenobarbital, ritonavir) with Exjade. If you must co-administer these agents together, consider increasing the initial dose of Exjade to 30mg/kg, and monitor serum ferritin levels and clinical responses for further dose modification[see Drug Interactions (7.4, 7.5)].
Hepatic Impairment
Avoid the use of Exjade in patients with severe (Child-Pugh C) hepatic impairment. Reduce the starting dose by 50% in patients with moderate (Child-Pugh B) hepatic impairment. Closely monitor patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment for efficacy and adverse reactions that may require dose titration [see Warnings and Precautions (5.2), and Use in Specific Populations (8.7).
3 DOSAGE FORMS AND STRENGTHS
125mg tablets
Off-white, round, flat tablet with beveled edge and imprinted with “J” and “125” on one side and “NVR” on the other.
250mg tablets
Off-white, round, flat tablet with beveled edge and imprinted with “J” and “250” on one side and “NVR” on the other.
500mg tablets
Off-white, round, flat tablet with beveled edge and imprinted with “J” and “500” on one side and “NVR” on the other.
4 CONTRAINDICATIONS
Exjade is contraindicated in patients with:
creatinine clearance <40 mL/min or serum creatinine >2 times the age-appropriate upper limit of normal;
poor performance status and high-risk myelodysplastic syn |
