EXJADE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EXJADE (EXJADE).
Deferasirox is an oral iron chelator that binds iron with high affinity in a 2:1 ratio. It promotes excretion of iron primarily in the feces via bile, reducing total body iron stores.
| Metabolism | Primarily metabolized via glucuronidation by UGT1A1, UGT1A3, and to a lesser extent UGT1A7, UGT1A8, and UGT2B7. Minimal CYP450 involvement (<10%). |
| Excretion | Primarily fecal (84% of total clearance), with ~8% renal (as unchanged drug and metabolites). |
| Half-life | Terminal elimination half-life is 8–16 hours, supporting once-daily dosing. |
| Protein binding | Deferasirox is highly protein bound (99%) primarily to albumin. |
| Volume of Distribution | Apparent volume of distribution is 0.28–0.4 L/kg in adults, indicating moderate tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 70% (tablet formulation), with a 30% lower bioavailability for the oral suspension. |
| Onset of Action | Oral: Clinical effect (serum ferritin reduction) typically seen after weeks of continuous dosing; no immediate effect. |
| Duration of Action | Duration of chelation covers the 24-hour dosing interval with sustained iron mobilization; clinical effects persist with continued use. |
20-40 mg/kg orally once daily, titrated based on serum ferritin trends, maximum 40 mg/kg per day.
| Dosage form | TABLET, FOR SUSPENSION |
| Renal impairment | For GFR 40-60 mL/min: start at 50% of recommended dose, titrate cautiously. For GFR <40 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: not recommended. |
| Pediatric use | For children aged 2-17 years: initial dose 20 mg/kg orally once daily, titrate up to 40 mg/kg per day based on serum ferritin. |
| Geriatric use | No specific adjustments recommended; use lowest effective dose with monitoring of renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EXJADE (EXJADE).
| Breastfeeding | Deferasirox is excreted in human milk. The milk-to-plasma (M/P) ratio is unknown. Due to potential serious adverse reactions in nursing infants, including iron chelation and nephrotoxicity, breast-feeding is not recommended during treatment with deferasirox. |
| Teratogenic Risk | Pregnancy Category C. In animal studies, deferasirox has been shown to be embryotoxic and teratogenic at maternally toxic doses, including increased incidence of skeletal variations and malformations. There are no adequate and well-controlled studies in pregnant women. Potential fetal risks include spontaneous abortion, fetal growth restriction, and skeletal anomalies. Risk is highest during the first trimester; however, deferasirox should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
WARNING: RENAL AND HEPATIC TOXICITY, INCLUDING FATALITIES. Acute renal failure, proteinuria, and renal tubular toxicity have been reported. Hepatic toxicity including fatal events has occurred. Monitor renal and hepatic function closely. Dose reduction, interruption, or discontinuation may be required. Avoid use in patients with severe renal or hepatic impairment.
| Serious Effects |
["Hypersensitivity to deferasirox or any component of the formulation","Serum creatinine >2 times the age-appropriate upper limit of normal (severe renal impairment)","CrCl <30 mL/min (including hemodialysis patients)","High-risk myelodysplastic syndrome (MDS) patients with advanced disease or those not responding to other therapies","Concomitant use with other iron chelators is not recommended except as part of a monitored switch"]
| Precautions | ["Renal toxicity: Acute renal failure, Fanconi syndrome, and renal tubular necrosis. Monitor serum creatinine and proteinuria monthly","Hepatic toxicity: Elevated liver enzymes, hepatitis, and hepatic failure. Monitor liver function tests monthly","Gastrointestinal hemorrhage: Risk of upper GI ulceration and bleeding, especially in patients with prior GI conditions or those taking NSAIDs, anticoagulants, or corticosteroids","Cytopenias: May cause severe neutropenia, agranulocytosis, and thrombocytopenia. Monitor blood counts regularly","Hypersensitivity reactions: Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS)","Auditory and ocular disturbances: Hearing loss and visual disturbances; perform audiometric and ophthalmic exams before and during treatment","Growth retardation: In children, growth and development should be monitored"] |
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| Fetal Monitoring | Monitor complete blood count (CBC), renal function (serum creatinine, BUN, urine protein), and liver function tests (ALT, AST, bilirubin) monthly. Assess serum ferritin levels every 3 months. Monitor for gastrointestinal hemorrhage, skin rash, and auditory/ocular disturbances. In pregnancy, consider fetal ultrasound for growth and anatomy due to potential teratogenicity. |
| Fertility Effects | Preclinical studies in animals have shown impaired fertility and reduced reproductive performance at high doses. In humans, no formal fertility studies have been conducted; however, deferasirox may affect reproductive function. Oligospermia has been reported in some patients. |