• Chronic iron overload due to blood transfusions.
• Chronic iron overload in non-transfusion-dependent thalassemia syndromes in patients with a liver iron concentration of 5 mg/g of liver dry weight and a serum ferritin >300 mcg/L.

Contraindicated in:

• Hypersensitivity
• CCr <40 mL/min or serum creatinine >2 times the upper limit of normal
• Poor performance status
• High-risk myelodysplastic syndromes or advanced malignancies
• Platelet count <50,000/mm³
• Severe hepatic impairment
• Lactation: Lactation.

Use Cautiously in:

• Renal impairment (↑ risk of worsening renal function)
• Mild or moderate hepatic impairment
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Pedi: Children <2 yr (safety and effectiveness not established); ↑ risk of GI hemorrhage in children
• Geri: ↑risk of renal/hepatic impairment in older adults; ↑ risk of GI hemorrhage in older adults with malignancy and/or low platelet counts.

Derm: rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS.

EENT: ↑intraocular pressure, cataracts, hearing loss, lens opacities, retinal disorders.

GI: diarrhea, nausea , vomiting, ↑ liver enzymes, abdominal pain, drug-induced hepatitis, GI BLEEDING/ULCERATION, GI PERFORATION, HEPATOTOXICITY.

GU: ↑serum creatinine, renal failure.

Hemat: agranulocytosis, neutropenia, thrombocytopenia, worsening anemia.

MS: arthralgia.

Neuro: headache, dizziness.

Resp: cough.
Misc: fever, (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)HYPERSENSITIVITY REACTIONS .

Drug-Drug:

• Aluminum-containing antacids may ↓ levels and effectiveness.
• Cholestyramine, rifampin, phenytoin, phenobarbital, and ritonavir may ↓ levels and effectiveness; avoid concurrent use or ↑ deferasirox dose.
• Avoid concurrent use with other iron chelators.
• ↑risk of GI bleeding or ulceration with NSAIDs, corticosteroids, bisphosphonates, or anticoagulants.
• May ↓ levels and effectiveness of CYP3A4 substrates.
• May ↑ levels of and risk of hypoglycemia with repaglinide; ↓ dose of repaglinide.
• May ↑ levels and risk of toxicity of theophylline; avoid concurrent use or ↓ theophylline dose.
• May ↑ levels and risk of toxicity of CYP1A2 substrates, including cyclobenzaprine, imipramine, haloperidol, fluvoxamine, mexiletine, olanzapine, tizanidine, zileuton, and zolmitriptan.
• May ↑ levels and risk of toxicity of busulfan; monitor busulfan levels and adjust busulfan dose as needed.

(Generic available)

• Sprinkle granules (Jadenu): 90 mg/sachet; 180 mg/sachet; 360 mg/sachet;
• Tablets (Jadenu): 90 mg; 180 mg; 360 mg;
• Tablets for oral suspension (Exjade): 125 mg; 250 mg; 500 mg;

Chronic Iron Overload Due to Blood Transfusions

• PO (Adults and Children 2 yr): Exjade: 20 mg/kg once daily; adjusted by 5–10 mg/kg every 3–6 mo on the basis of serum ferritin levels (not to exceed 40 mg/kg/day); Jadenu: 14 mg/kg once daily; adjusted by 3.5–7 mg/kg every 3–6 mo on the basis of serum ferritin levels (not to exceed 28 mg/kg/day).

Chronic Iron Overload in Non-Transfusion-Dependent Thalassemia Syndromes

• PO (Adults and Children 10 yr): Exjade: 10 mg/kg once daily; if baseline liver iron concentration (LIC) >15 mg/g of liver dry weight, consider ↑ dose to 20 mg/kg/day after 4 wk. If liver iron concentration remains >7 mg/g of liver dry weight after 6 mo, ↑ dose to 20 mg/kg/day (maximum dose). If LIC is 3–7 mg/g of liver dry weight after 6 mo, continue therapy with no more than 10 mg/kg/day. When LIC <3 mg/g of liver dry weight, may discontinue therapy (restart when liver iron concentration >5 mg/g of liver dry weight); Jadenu: 7 mg/kg once daily; if baseline LIC >15 mg/g of liver dry weight, consider ↑ dose to 14 mg/kg/day after 4 wk. If LIC remains >7 mg/g of liver dry weight after 6 mo, ↑ dose to 14 mg/kg/day (maximum dose). If LIC is 3–7 mg/g of liver dry weight after 6 mo, continue therapy with no more than 7 mg/kg/day. When LIC <3 mg/g of liver dry weight, may discontinue therapy (restart when LIC >5 mg/g of liver dry weight).

Exjade, Jadenu

• Selectively chelates iron and eliminates it in feces.

• Decreased iron with decreased sequelae of iron excess (hemosiderosis).

Therapeutic Classification: antidotes

Pharmacologic Classification: chelating agents

Absorption: Well absorbed (70%) following oral administration; absorption is less in children.

Distribution: Unknown.

Protein Binding: 99%.

Metabolism/Excretion: Mostly metabolized by the liver, followed by enterohepatic recycling. 84% excreted in feces (deferasirox and metabolites); minimal renal excretion.

Half-life: 8–16 hr.

(plasma concentrations)

• Instruct patient to take deferasirox as directed at same time each day.
• Advise patient not to take aluminum-containing antacids with deferasirox.
• May cause dizziness. Advise patient to avoid driving and other activities requiring alertness until response to medication is known.
• Advise patient to maintain adequate hydration if vomiting or diarrhea occurs.
• Advise patient to notify health care professional if signs and symptoms of liver problems (drowsiness, upper right abdominal pain, yellowing or increased yellowing of skin or eyes, dark urine), allergic reaction (difficulty breathing or swallowing; chest pain; rapid heartbeat; feeling faint; swelling of face, lips, mouth, tongue, or throat; severe itching of the skin with a red rash or raised bumps; hives), DRESS (rash or red skin, blisters on lips or around mouth or eyes, mouth sores, skin peeling, high fever, flu-like symptoms, enlarged lymph nodes), stomach pain, bleeding, or changes in vision or hearing occur.
• Advise parents of children taking deferasirox to notify health care professional immediately if child develops fever, vomiting, or diarrhea and cannot drink fluids normally, or is passing less urine than normal; child may be dehydrated.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products, especially NSAIDs, corticosteroids, oral bisphosphonates, or anticoagulants.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. Caution patient to use nonhormonal contraceptive, as deferasirox ↓ effectiveness of hormonal contraceptives.

de-fe-RA-si-rox