Jadenu

Deferasirox

Management of chronic Fe overload in patients w/ transfusion-dependent anemias aged ≥6 yr; in patients w/ transfusion-dependent anemias aged 2-5 yr who cannot be adequately treated w/ deferoxamine. Treatment of chronic Fe overload in patients w/ non-transfusion-dependent thalassemia syndromes aged ≥10 yr.

Transfusional Fe overload Patient receiving <7 mL/kg/mth of packed RBC & for whom the objective is maintenance of an acceptable body Fe level Initially 7 mg/kg daily. Patient receiving >7 mL/kg/mth of packed RBC & for whom the objective is maintenance of an acceptable body Fe level Initially 14 mg/kg daily. Patient receiving <14 mL/kg/mth of packed RBC & for whom the objective is gradual reduction of Fe overload Initially 14 mg/kg daily. Patient receiving >14 mL/kg/mth of packed RBC & for whom the objective is gradual reduction of Fe overload Initially 21 mg/kg daily. Dose adjustment: Adjust dose if necessary every 3-6 mth in steps of 3.5 or 7 mg/kg. Non-transfusion-dependent thalassemia syndromes Initially 7 mg/kg. May be adjusted every 3-6 mth in 3.5-7 mg/kg increments.

Should be taken on an empty stomach: Take on an empty stomach or w/ a light meal. Swallow whole w/ water or other liqd. May crush tab & sprinkle full dose on a soft food.

Hypersensitivity. Estimated CrCl <60 mL/min or serum creatinine >2 times the age-appropriate ULN. High risk myelodysplastic syndrome (MDS) patients, any other MDS patient w/ a life expectancy <1 yr & patients w/ other hematological & non-hematological malignancies who are not expected to benefit from chelation therapy due to the rapid progression of their disease. Platelet counts <50 x 10⁹/L.

Discontinue treatment in case of hypersensitivity reactions or suspected severe cutaneous adverse reactions. Reports of auditory disturbances (high-frequency hearing loss, decreased hearing); ocular disturbances (lens opacities, early cataracts, maculopathies); cytopenias; hepatic failure, acute pancreatitis; acute renal failure; renal tubulopathy. Risk of GI irritation; acute kidney injury; skin rashes. Increased risk of toxicity when inappropriately given to patients w/ low Fe burden or w/ serum ferritin levels that are only slightly elevated. Monitor blood counts regularly. Monitor serum transaminases, bilirubin & alkaline phosphatase before initiation of treatment, every 2 wk during the 1st mth & mthly thereafter. Monitor renal function more frequently in patients w/ pre-existing renal disease or decreased renal function. Monitor liver & renal function more frequently during vol depletion & in patients receiving Jadenu 14-28 mg/kg daily when Fe burden is approaching the normal range. Measure serum ferritin mthly. Assess serum creatinine & CrCl twice before initiating therapy, & monitor wkly in the 1st mth after initiation or modification of therapy, & mthly thereafter. Perform mthly tests for proteinuria. Safety of Jadenu when administered w/ other Fe chelation therapy has not been established. Caution w/ concomitant use of drugs known to have ulcerogenic potential (eg, NSAIDs, corticosteroids, or oral bisphosphonates); anticoagulants. Not recommended in patients w/ acute cardiac failure due to Fe overload; severe hepatic impairment. Caution in patients w/ elevated serum creatinine levels. Patients experiencing dizziness should exercise caution when driving or operating machinery. Should not be used during pregnancy. Women should be advised against breast-feeding while on therapy. Limited data in childn 2-5 yr. Higher frequency of adverse reactions in elderly patients.

Diarrhea, vomiting, nausea, headache, constipation, dyspepsia, abdominal pain, pyrexia, cough, proteinuria, increases in serum creatinine & transaminases, pruritus & skin rash.

Do not co-administer w/ other Fe chelator or Al-containing antacid prep. Possible decrease in efficacy of CYP3A4 substrates (eg, cyclosporine, simvastatin, hormonal contraceptive agents). Decreased efficacy w/ potent UGT inducers (eg, rifampicin, phenytoin, phenobarb, ritonavir). Decreased exposure w/ cholestyramine. Increased AUC & C_max of repaglinide (CYP2C8 substrate). Increased AUC of theophylline (CYP1A2 substrate). Interaction w/ other CYP1A2 substrates (eg, clozapine & tizanidine) may be possible. Increased exposure of busulfan. High doses of vit C (>200 mg) should not be used. Increased risk of GI irritation w/ ulcerogenic potential drugs (eg, NSAIDs, corticosteroids, oral bisphosphonates); anticoagulants. Increased exposure w/ high-fat meal. Results of gallium-67 imaging may be distorted.

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.

P₁S₁S₃