Usage
Deferasirox is prescribed for the treatment of chronic iron overload caused by blood transfusions (transfusional iron overload) in patients 2 years of age and older, and for chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia syndromes (NTDT). It is classified as an iron chelator. Deferasirox works by binding to iron in the bloodstream, which helps facilitate its removal from the body. This reduces the risk of iron-induced organ damage.
Alternate Names
Deferasirox is the generic name. Brand names include Exjade (tablets, dispersible tablets, and granules for oral suspension) and Jadenu (film-coated tablets).
How It Works
Pharmacodynamics: Deferasirox exerts its therapeutic effect by chelating iron. It forms a stable complex with ferric iron (Fe3+) in a 2:1 ratio, facilitating iron excretion primarily through the feces via biliary excretion. It reduces liver iron concentration (LIC) and serum ferritin levels, thereby preventing or reducing iron-mediated organ damage.
Pharmacokinetics:
- Absorption: Deferasirox is absorbed orally with peak plasma concentrations reached approximately 1 to 4 hours after administration. Food can affect the absorption of deferasirox.
- Metabolism: Deferasirox is mainly glucuronidated, primarily by UGT1A1, in the liver.
- Elimination: Deferasirox is predominantly eliminated in the feces via biliary excretion, with minimal renal excretion. The elimination half-life is approximately 12-19 hours.
Mode of Action: Deferasirox selectively binds to iron, forming a stable complex. This complex is then excreted from the body, primarily via the biliary route into the feces.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Deferasirox’s primary mechanism is iron chelation. There is no significant receptor binding, enzyme inhibition, or neurotransmitter modulation associated with its therapeutic action.
Elimination Pathways: Primarily hepatic metabolism and biliary excretion into feces, with minimal renal excretion.
Dosage
Standard Dosage
Adults:
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Transfusional Iron Overload: The initial recommended dose is 20 mg/kg once daily. The dose can be adjusted based on the patient’s response to therapy and iron burden, up to a maximum of 40 mg/kg daily.
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NTDT: The maximum recommended dose is 10 mg/kg daily.
Children:
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Transfusional Iron Overload (2 years and older): The initial recommended dose is 14 mg/kg once daily. The dose can be adjusted based on the patient’s response and iron burden, up to a maximum of 40 mg/kg daily.
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NTDT (10 years and older): The maximum recommended dose is 10 mg/kg daily.
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Children younger than 2 years: The safety and efficacy have not been established for transfusional iron overload. Deferasirox is not recommended for NTDT in children younger than 10 years of age.
Special Cases:
- Elderly Patients: Elderly patients may be more prone to adverse effects, particularly diarrhea. Close monitoring for side effects and dose adjustments may be necessary.
- Patients with Renal Impairment: Deferasirox is contraindicated in patients with estimated creatinine clearance (CrCl) < 40 mL/min. Dose reduction is recommended for patients with CrCl < 60 mL/min.
- Patients with Hepatic Dysfunction: Avoid use in patients with severe hepatic impairment (Child-Pugh C). Dose reduction is recommended in patients with moderate hepatic impairment (Child-Pugh B).
- Patients with Comorbid Conditions: Careful monitoring is advised for patients with pre-existing renal or hepatic conditions, gastrointestinal issues, or other comorbidities.
Clinical Use Cases
Deferasirox is not indicated for use in intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is in the chronic management of iron overload.
Dosage Adjustments
Dose adjustments may be necessary based on serum ferritin levels, LIC, and patient tolerance. Close monitoring of renal and liver function is essential.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, abdominal pain, rash, headache.
Rare but Serious Side Effects
Kidney failure, liver failure, gastrointestinal hemorrhage, severe skin reactions (e.g., Stevens-Johnson Syndrome, toxic epidermal necrolysis), vision or hearing changes.
Long-Term Effects
Chronic kidney disease, liver disease, cataracts, growth retardation in children.
Adverse Drug Reactions (ADR)
Any signs of renal or hepatic impairment, gastrointestinal bleeding, severe skin reactions, vision or hearing changes should prompt immediate medical attention.
Contraindications
- Hypersensitivity to deferasirox.
- Severe renal impairment (eGFR < 40 mL/min).
- Severe hepatic impairment (Child-Pugh C).
- Concomitant use with other iron chelators.
Drug Interactions
- Antacids containing aluminum.
- Midazolam, rifampin, cyclosporine, cholestyramine, simvastatin, phenytoin, warfarin, repaglinide.
- Certain NSAIDs (e.g., ibuprofen, naproxen) can increase the risk of gastrointestinal bleeding.
Pregnancy and Breastfeeding
- Pregnancy: Deferasirox should be avoided during pregnancy unless the potential benefit outweighs the risk to the fetus. Animal studies have shown some adverse effects.
- Breastfeeding: Data on human milk excretion is limited. A decision should be made to discontinue breastfeeding or the drug, taking into account the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: Iron chelator that binds to iron and facilitates its elimination primarily through biliary excretion.
- Side Effects: Common: nausea, vomiting, diarrhea, abdominal pain, rash, headache. Serious: renal failure, liver failure, GI hemorrhage.
- Contraindications: Hypersensitivity, severe renal or hepatic impairment, concomitant use with other iron chelators.
- Drug Interactions: Antacids, midazolam, rifampin, cyclosporine, cholestyramine, simvastatin, phenytoin, warfarin, repaglinide, NSAIDs.
- Pregnancy & Breastfeeding: Generally avoided.
- Dosage: Variable based on age, iron burden, and clinical response. See detailed dosage section.
- Monitoring Parameters: Renal function (serum creatinine, eGFR), liver function tests (ALT, AST, bilirubin), serum ferritin, LIC, complete blood count.
Popular Combinations
Deferasirox is typically used as monotherapy. Combining it with other iron chelators is contraindicated.
Precautions
- Monitor renal and liver function closely.
- Monitor for signs of gastrointestinal bleeding.
- Patients with pre-existing organ dysfunction, advanced hematologic malignancies, or low platelet counts require extra caution.
- Safety and efficacy in children under 2 years (transfusional overload) or 10 years (NTDT) have not been established.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Deferasirox?
A: The dosage varies depending on the patient’s age, iron burden, and underlying condition. See the detailed dosage guidelines provided above.
Q2: How is Deferasirox administered?
A: Deferasirox is administered orally once daily. Tablets can be swallowed whole or crushed and mixed with soft food (e.g., yogurt, applesauce) for patients who have difficulty swallowing tablets. The mixture should be consumed immediately.
Q3: What are the most serious side effects of Deferasirox?
A: The most serious side effects include renal failure, liver failure, and gastrointestinal hemorrhage. Patients should be monitored closely for these complications.
Q4: Can Deferasirox be used during pregnancy?
A: Deferasirox should generally be avoided during pregnancy unless the potential benefit outweighs the risk to the fetus. Discuss the risks and benefits with a specialist.
Q5: How does Deferasirox interact with antacids?
A: Antacids containing aluminum can reduce the absorption of Deferasirox. These medications should not be taken at the same time.
Q6: What monitoring is required during Deferasirox therapy?
A: Regular monitoring of renal and liver function, serum ferritin, LIC, and complete blood count is essential during Deferasirox treatment.
Q7: Can Deferasirox be used in patients with pre-existing kidney disease?
A: Deferasirox is contraindicated in patients with severe renal impairment (eGFR < 40 mL/min). Dose adjustments are necessary for patients with mild to moderate renal impairment.
Q8: What is the mechanism of action of Deferasirox?
A: Deferasirox chelates iron, forming a complex that is primarily eliminated in the feces via the biliary route.
Q9: What should I do if a patient misses a dose of Deferasirox?
A: If a dose is missed, it should be taken as soon as remembered, even if later in the day. Do not double the dose the next day.
Q10: Is Deferasirox compatible with other iron chelators?
A: No, Deferasirox should not be used concomitantly with other iron chelators.
