Information for the Physician

Indications

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

When to Initiate Therapy

When a patient has evidence of chronic iron overload (e.g. transfusion of approximately 100 mL/kg of packed RBCs (approximately 20 units for a 40 kg patient), and
Serum ferritin is consistently >1000 mcg/L. the nsk for toxicity may be increased when deferasirox is given to patients with low iron burden or with serum ferritin levels that are only slightly elevated.

Starting Dose

The recommended initial daily dose is 20 mg/kg body weight.

Dose Modifications

DESIROX may require dose adjustment, interruption or cessation of therapy due to toxicity or any of the following

Based on Serum Ferritin

After commencing initial therapy, monitor serum ferritin every month and adjust the dose if necessary every 3-6 months based on serum ferritin trends.
Make dose adjustments in steps of 5 or 10 mg/kg and tailor adjuments to the individual patient's response and therapeutic goals (maintenance or reduction of body iron burden).
In patients not adequately controlled with doses of 30 mg/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/kg may be considered.
Doses above 40 mg/kg are not recommended.
If the serum ferritin falls consistently below 500 mcg/L consider temporanly interrupting therapy.

Based on Serum Creatinine

For adults, reduce the daily dose of DESIROX by 10 mg/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 10 mg/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 DESIROX.
If you must co-administer these agents together, consider increasing the initial dose of DESIROX to 30 mg/kg, and monitor serum ferritin levels and clinical responses for further dose modification

Hepatic Impairment

Avoid the use of DESIROX 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.

How to Administer Desirox

Take once daily on an empty stomach, at least 30 minutes before food, preferably at the same time each day.
Doses (mg/kg per day) should be calculated to the nearest whole tablet Tablets should not be chewed or swallowed whole.
Tablets should be completely dispersed by stirring in water, orange juice, or apple juice until a fine suspension is obtained.
After swallowing the suspension, any residue should be resuspended in a small volume of liquid and swallowed.
Doses of <1 g should be dispersed In about 100 ml (3.5 ounces) of liquid and doses of> 1 g in about 200 ml (7.0 ounces) of liquid.
DESIROX should not be taken with aluminum-containing antacid products.

Monitoring Guidelines

*ln patients with underlying renal impairment/risk factors for renal impairment, monitor weekly for the first month then monthly thereafter.

Contraindications

DESIROX is contraindicated in patients with:

Creatinine clearance <40 mL/mm or serum creatinine>2 times the age-appropriate upper limit of normal
Poor performance status and high-risk myelodysplastic syndromes or advanced malignancies
Platelet counts <50 x 10⁹-/L
Known hypersensitivity to deferasirox or any component of DESIROX