Introduction
Jadenu (deferasirox) is an oral iron chelating agent used for the treatment of chronic iron overload in patients receiving blood transfusions. It represents a significant advancement in iron chelation therapy, offering once-daily oral administration as an alternative to previous parenteral options. Jadenu is specifically formulated as a dispersible tablet designed to improve tolerability compared to the original Exjade formulation.
Mechanism of Action
Deferasirox selectively binds iron with high affinity (2:1 ratio), forming a stable complex that is excreted primarily through fecal elimination. The drug acts by crossing cell membranes and chelating iron from labile pools and storage sites, particularly within hepatocytes and cardiac cells. Unlike some other chelators, deferasirox shows relative specificity for iron over other essential metals like zinc and copper, though monitoring of these metals is still recommended during long-term therapy.
Indications
- Treatment of chronic iron overload due to blood transfusions in patients 2 years and older
- Treatment of chronic iron overload in non-transfusion-dependent thalassemia syndromes in patients 10 years and older
Dosage and Administration
Initial Dosing:- Transfusion-dependent iron overload: 20 mg/kg orally once daily
- Non-transfusion-dependent thalassemia: 10 mg/kg orally once daily
- Based on serum ferritin levels and treatment response
- May be increased by 5-10 mg/kg increments every 3-6 months
- Maximum recommended dose: 40 mg/kg daily
- Take on an empty stomach at least 30 minutes before food
- Tablets should be dispersed in water, apple juice, or orange juice
- Administer the entire dispersed content immediately
- Do not chew or swallow whole tablets
- Renal impairment: Use with caution; dose reduction recommended
- Hepatic impairment: Use with caution; monitor closely
- Elderly: Consider potential for decreased renal function
- Pediatric: Safety established down to age 2 years
Pharmacokinetics
Absorption: Rapidly absorbed with peak concentrations achieved in 1.5-4 hours. Bioavailability is approximately 70%. Distribution: Highly protein-bound (~99%) to albumin. Volume of distribution is 14.37 ± 2.69 L in adults. Metabolism: Primarily hepatic metabolism via glucuronidation by UGT1A1 and UGT1A3, with subsequent biliary excretion. Elimination: Primarily fecal excretion (84%) with minimal renal elimination (8%). Elimination half-life ranges from 8-16 hours.Contraindications
- Patients with hypersensitivity to deferasirox or any component of the formulation
- Patients with creatinine clearance <40 mL/min or severe renal impairment
- Patients with high-risk myelodysplastic syndrome or advanced malignancies
- Patients with poor performance status
- Patients with hepatic impairment (Child-Pugh Class C)
Warnings and Precautions
Renal Effects: May cause renal tubular damage leading to acute renal failure. Monitor serum creatinine regularly and consider dose interruption or reduction for increases above baseline. Hepatic Effects: May cause hepatic toxicity including hepatitis. Monitor transaminases and bilirubin regularly. GI Hemorrhage: May cause gastrointestinal ulceration, hemorrhage, and perforation, particularly in elderly patients. Auditory and Ocular Effects: May cause auditory disturbances (high-frequency hearing loss) and ocular disturbances (lens opacities, cataracts). Cytopenias: May cause neutropenia, agranulocytosis, and thrombocytopenia. Monitor blood counts regularly.Drug Interactions
UDP-glucuronosyltransferase (UGT) inducers: Rifampicin, phenytoin, phenobarbital, and ritonavir may decrease deferasirox concentrations. UGT inhibitors: Atazanavir and other UGT inhibitors may increase deferasirox concentrations. Antacids containing aluminum: May decrease deferasirox absorption. Separate administration by at least 2 hours. CYP3A4 substrates: Deferasirox may decrease concentrations of midazolam, simvastatin, and other CYP3A4 substrates. Cholestyramine: May decrease deferasirox absorption. Avoid concomitant use.Adverse Effects
Common (≥10%):- Nausea (15%)
- Vomiting (12%)
- Abdominal pain (12%)
- Diarrhea (10%)
- Serum creatinine increase (38%)
- Skin rash (11%)
- Acute renal failure
- Hepatic failure
- GI ulceration/hemorrhage
- Agranulocytosis
- Hearing loss
- Vision disturbances
Monitoring Parameters
Baseline and regular monitoring:- Serum ferritin (every 2-4 weeks until stable, then monthly)
- Serum creatinine (before initiation, then weekly for first month, then monthly)
- Liver function tests (before initiation, then every 2 weeks for first month, then monthly)
- Complete blood count with differential
- Auditory and ophthalmic examinations (annually)
- Urine protein (regularly)
- Maintain serum ferritin <1000 μg/L
- Adjust dose based on trends rather than single values
- Monitor for compliance and tolerability
Patient Education
- Take medication on an empty stomach 30 minutes before food
- Disperse tablet completely in water, apple juice, or orange juice
- Drink the entire suspension immediately; do not save for later use
- Report any signs of renal problems (decreased urine output, swelling)
- Report any signs of liver problems (jaundice, dark urine, abdominal pain)
- Report any hearing or vision changes
- Report any unusual bleeding or bruising
- Attend all scheduled monitoring appointments
- Do not take antacids within 2 hours of Jadenu administration
- Inform all healthcare providers about Jadenu use
References
1. Cappellini MD, Porter J, El-Beshlawy A, et al. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias. Haematologica. 2010;95(4):557-566.
2. Jadenu [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021.
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes. Version 2.2022.
4. Angelucci E, Li J, Greenberg PL, et al. Iron Chelation in Transfusion-Dependent Patients with Low- to Intermediate-1-Risk Myelodysplastic Syndromes: A Randomized Trial. Ann Intern Med. 2020;172(8):513-522.
5. Cappellini MD, Cohen A, Porter J, et al. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 3rd edition. Thalassaemia International Federation; 2014.
6. FDA Drug Safety Communication: Boxed warning and new recommendations for deferasirox (Exjade, Jadenu). U.S. Food and Drug Administration; 2017.
7. Porter JB, Cappellini MD, Kattamis A, et al. Iron overload across different tissues: clinical implications and emerging treatment strategies. Hemosphere. 2019;3(1):e125.
Note: This monograph provides general information and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.