Exsirox

Deferasirox

Chronic Fe overload due to transfusions (transfusional hemosiderosis) in ≥2 yr. Chronic Fe overload in ≥10 yr w/ non-transfusion-dependent thalassemia syndromes.

1 tab once daily. Adult & ped patients ≥2 yr Chronic Fe overload due to transfusions Initially 20 mg/kg once daily. Max: 40 mg/kg daily. Adjust the dose in increments 5-10 mg/kg for 3-6 mth if necessary based on serum ferritin trends. Patients not adequately controlled w/ doses of 30 mg/kg (eg, serum ferritin levels persistently >2,500 mcg/L & not showing a decreasing trend over time) Up to 40 mg/kg may be considered. Adult & ped patients ≥10 yr Chronic Fe overload in non-transfusion-dependent thalassemia syndromes Initially 10 mg/kg once daily. Max: 20 mg/kg daily. LIC >15 mg Fe/g dw Increase dose to 20 mg/kg daily after 4 wk. LIC >7 mg Fe/g dw Increase dose to max of 20 mg/kg daily after 6 mth. LIC 3-7 mg Fe/g dw Continue treatment at not >10 mg/kg daily. Renal toxic during treatment Chronic Fe overload due to transfusions Adult & adolescents ≥16 yr Reduce dose by 10 mg/kg if serum creatinine is still elevated by 33%. Childn 2-15 yr Reduce daily dose by 10 mg/kg for increased serum creatinine >33%. Chronic Fe overload in non-transfusion-dependent thalassemia syndrome Adult & adolescent ≥16 yr Reduce by 50% if the dose is 10 or 20 mg/kg if serum creatinine is still elevated by 33%. Childn 2-15 yr Reduce daily dose by 5 mg/kg if serum creatinine is >33% above baseline.

Should be taken on an empty stomach: Take at least 30 min before meals, preferably at the same time daily. Disperse the tab by stirring in 105 mL (w/ doses of < 1 g) & 210 mL (w/ doses of > 1 g) of water, orange or apple juice until a fine susp is obtained. After the susp has been drunk, any residue must be resuspended in a small vol of water, orange or apple juice & drunk. Do not chew or swallow the tab.

Hypersensitivity. Patients w/ CrCl <40 mL/min or serum creatinine >2 x the age-appropriate ULN; poor performance status; high-risk myelodysplastic syndromes; advanced malignancies; platelet counts <50,000/mm³.

Discontinue if severe hypersensitivity reactions occur. Acute renal failure (including fatalities & case requiring dialysis); patients w/ comorbid conditions & advanced hematologic malignancies. Obtain serum creatinine & calculate CrCl in duplicate at baseline prior to initiation & monitor at least mthly thereafter. Monitor creatinine wkly during the 1st mth & then at least mthly thereafter in patients w/ underlying renal dysfunction or at risk for acute renal failure. Consider dose reduction, interruption or discontinuation for serum creatinine elevations. May cause proteinuria. Fanconi syndrome, primarily in ped/adolescent patients w/ β-thalassemia & serum ferritin level <1,500 mcg/L. Hepatic injury & failure (including fatalities). Monitor transaminases & bilirubin at baseline, every 2 wk for 1 mth, then at least mthly thereafter. Reduce dose or temporarily interrupt treatment for severe or persistent increases in transaminases/bilirubin. Acute heart failure associated w/ Fe overload. Observe more frequently in elderly patients w/ advanced hematologic malignancies &/or low platelet counts; discontinue treatment for suspected GI hemorrhage or ulceration. Monitor patients closely for signs/symptoms of GI ulceration/bleeding. Concomitant use w/ NSAIDs, corticosteroids, anticoagulants, oral bisphosphonates; trace minerals eg, Zn & Cu. Increase risk of cytopenias in patients w/ preexisting hematologic disorders; monitor blood cell counts regularly. Contraindicated if platelet count <50,000/mm³; CrCl <40 mL/min or serum creatinine >2x age-appropriate ULN. Discontinue immediately & evaluate if skin rash (dose related) occurs. Perform auditory & ophth testing prior to initiation & regularly (every 12 mth) during use. Monitor more closely & consider dose reduction or treatment interruption if abnormalities develop. Hepatic & renal impairment. Avoid use in patients w/ severe (Child-Pugh class C) hepatic impairment; monitor mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment. Pregnancy & lactation. Elderly.

Skin rash; abdominal pain, diarrhea, nausea, vomiting; proteinuria; increase serum creatinine; fatigue; increase serum ALT; pharyngolaryngeal pain, resp tract infection.

May increase serum conc of agomelatine, CYP1A2, CYP2C8 & CYP3A4 substrates, pirfenidone, repaglinide, theophylline, tizanidine. May diminish therapeutic effect w/ Al hydroxide. May enhance adverse/toxic effect w/ bisphosphonate derivatives, anticoagulants, corticosteroids or NSAIDs. May decrease serum conc w/ bile acid sequestrants, fosphenytoin or phenytoin, phenobarb, rifampin, ritonavir.

Antidotes & Detoxifying Agents

V03AC03 - deferasirox ; Belongs to the class of iron chelating agents. Used in the management of chronic iron overload associated with blood transfusion.

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