1. Clinical Overview
Deferasirox is an oral, tridentate iron chelator used for the chronic treatment of transfusional iron overload in patients with conditions such as thalassemia, sickle cell disease, and other anemias. It selectively binds to iron (Fe³⁺) with high affinity, forming a stable complex (2:1 ratio) that is excreted primarily in feces, thereby reducing toxic iron accumulation in vital organs like the liver and heart.
| Onset | Duration | Bioavailability |
|---|---|---|
| Iron excretion begins within 24-48 hours of administration. | Approximately 24 hours, supporting once-daily dosing. | Approximately 70% when taken on an empty stomach. |
2. Mechanism of Action
Deferasirox is a tridentate, lipophilic ligand that selectively binds ferric iron (Fe³⁺) with high affinity (pFe³⁺ = 22.5). It forms a stable 2:1 (drug:iron) complex. This complex is neutral and lipophilic, allowing it to be excreted via the bile into the feces. By chelating excess iron from labile pools (like non-transferrin-bound iron - NTBI) and from storage sites (ferritin and hemosiderin), it prevents iron-mediated generation of reactive oxygen species (ROS) and subsequent tissue damage in organs like the liver, heart, and endocrine glands.
3. Indications & Uses
- Chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients aged 2 years and older with thalassemia syndromes.
- Chronic iron overload in patients aged 10 years and older with non-transfusion-dependent thalassemia (NTDT) syndromes and with a liver iron concentration (LIC) ≥ 5 mg Fe/g dry weight.
4. Dosage & Administration
Adult Dosage: Initial dose: 10-20 mg/kg body weight orally once daily. Dose is titrated based on transfusional iron intake and therapeutic goals (serum ferritin trend, LIC). Maintenance: Typically 20-30 mg/kg/day. Maximum starting dose is 20 mg/kg/day.
Administration: Take on an empty stomach, at least 30 minutes before food, preferably at the same time each day. DISPERSIBLE TABLET: Disperse completely in water, orange juice, or apple juice (100-200 mL). Stir to form a suspension and drink immediately. Do not chew or swallow whole tablet. Residue can be re-suspended in a small volume of liquid and consumed. FILM-COATED TABLET: Swallow whole with water. Do not chew or crush.
5. Side Effects
Common side effects may include:
- Nausea
- Abdominal pain
- Diarrhea
- Vomiting
- Skin rash
- Headache
- Increased serum creatinine
- Proteinuria
- Upper respiratory tract infection
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Aluminum-containing antacids | Decreased absorption of deferasirox. Separate administration by at least 4 hours. | Moderate |
| Cholestyramine | May decrease deferasirox absorption. Avoid concomitant use. | Moderate |
| 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. Avoid combination or monitor glucose closely. | Major |
| Theophylline | Deferasirox may increase theophylline levels, increasing toxicity risk. Monitor theophylline concentration. | Moderate |
| Vitamin C (high doses >200mg) | May increase iron toxicity and tissue iron deposition. Avoid high-dose supplementation. | Moderate |
| Other hepatotoxic or nephrotoxic drugs (e.g., NSAIDs, Aminoglycosides) | Increased risk of combined organ toxicity. Monitor renal and liver function closely. | Major |
7. Patient Counselling
- DO take the medicine on an empty stomach, at least 30 minutes before any food or drink (except water).
- DO disperse the tablet completely in water, apple juice, or orange juice as instructed. 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 problems, unusual bleeding, severe stomach pain, or persistent vomiting/diarrhea immediately.
- DONT chew or swallow the dispersible tablet whole.
- DONT take antacids, vitamins, or mineral supplements within 4 hours of taking deferasirox.
- DONT stop or change the dose without consulting your doctor.
8. Toxicology & Storage
Overdose: Acute overdose may manifest as symptoms of GI irritation (nausea, vomiting, abdominal pain, diarrhea), acute renal failure, hepatic dysfunction, and hearing loss. Lethargy and coma have been reported in massive overdose.
Storage: Store below 30°C. Keep the tablets in the original blister pack or bottle to protect from moisture. Keep out of reach of children. Do not use after the expiry date printed on the pack.