1. Clinical Overview
Deferasirox is a once-daily, oral iron chelator used for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years and older, and for the treatment of non-transfusion-dependent thalassemia (NTDT) syndromes with a liver iron concentration (LIC) of at least 5 mg Fe/g dry weight and a serum ferritin > 300 mcg/L. It is a tridentate ligand that binds iron with high selectivity in a 2:1 ratio.
| Onset | Duration | Bioavailability |
|---|---|---|
| Therapeutic effect on iron excretion begins within 24-48 hours of administration. | Approximately 24 hours, supporting once-daily dosing. | Approximately 70% when taken on an empty stomach. Reduced significantly with food, especially high-fat meals. |
2. Mechanism of Action
Deferasirox selectively binds ferric iron (Fe3+) with high affinity (pFe3+ = 22.5) in a 2:1 (drug:iron) ratio, forming a stable complex. This complex is then excreted primarily in the feces via biliary elimination, thereby reducing the toxic accumulation of iron in tissues (liver, heart, endocrine glands).
3. Indications & Uses
- Chronic iron overload due to multiple blood transfusions (≥7 ml/kg/month of packed RBCs) in patients aged 2 years and older (e.g., Thalassemia Major, Myelodysplastic Syndromes, Sickle Cell Disease, Aplastic Anemia).
- Non-transfusion-dependent thalassemia (NTDT) syndromes (e.g., β-thalassemia intermedia) with liver iron concentration (LIC) ≥ 5 mg Fe/g dry weight and serum ferritin > 300 mcg/L.
4. Dosage & Administration
Adult Dosage: Initial: 20 mg/kg body weight orally once daily. Titration: Adjust by 5 or 10 mg/kg increments every 3-6 months based on serum ferritin trends and safety. Maintenance: Typically 20-40 mg/kg/day. Max: 40 mg/kg/day.
Administration: Take on an empty stomach, at least 30 minutes before food, preferably at the same time each day. The 180mg tablet must be dispersed in a glass of water, orange juice, or apple juice (100-200 mL). Stir to form a fine suspension and drink immediately. Do not chew, swallow whole, or take with antacids containing aluminum.
5. Side Effects
Common side effects may include:
- Nausea
- Abdominal pain
- Diarrhea
- Vomiting
- Skin rash
- Headache
- Increased serum creatinine
- Proteinuria
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Aluminum-containing Antacids | Decreased absorption of deferasirox. Separate administration by at least 4 hours. | Major |
| Cholestyramine | May decrease deferasirox absorption. Avoid concomitant use. | Major |
| Potent UGT inducers (e.g., Rifampicin, Phenytoin, Phenobarbital, Ritonavir) | May decrease deferasirox plasma concentration, reducing efficacy. Monitor serum ferritin and consider dose increase. | Moderate |
| Repaglinide | Deferasirox may increase repaglinide exposure, increasing hypoglycemia risk. Use with caution and monitor blood glucose. | Moderate |
| Theophylline | Deferasirox may increase theophylline exposure. Monitor theophylline levels and reduce dose if needed. | Moderate |
| Warfarin | Potential for increased INR and bleeding risk. Monitor INR closely. | Moderate |
| CYP3A4 substrates with narrow therapeutic index (e.g., Ciclosporin, Simvastatin) | Deferasirox may reduce their plasma concentration. Monitor drug levels or effect. | Moderate |
| Other Hepatotoxic or Nephrotoxic drugs (e.g., NSAIDs, Aminoglycosides) | Increased risk of combined organ toxicity. Avoid or monitor closely. | Major |
7. Patient Counselling
- DO take the tablet on an empty stomach, at least 30 minutes before food.
- DO disperse the tablet completely in water, orange juice, or apple juice and drink the entire suspension immediately.
- DO have regular blood tests for kidney function, liver function, and serum ferritin as advised by your doctor.
- DO report any hearing changes, vision changes, unexplained bleeding, severe stomach pain, or rash immediately.
- DON'T chew, swallow, or break the tablet.
- DON'T take with antacids. Separate by at least 4 hours.
- DON'T take with food or milk products.
8. Toxicology & Storage
Overdose: Acute overdose may present with symptoms of GI irritation (nausea, vomiting, abdominal pain), acute renal failure, hepatic dysfunction, and hearing loss. Chronic overdose leads to excessive iron excretion, potentially causing depletion of essential iron stores and neutropenia.
Storage: Store below 30°C. Keep in the original blister pack or bottle to protect from moisture. Keep out of reach and sight of children.