Introduction
Deferasirox is an oral iron chelator used to reduce chronic iron overload in patients receiving long-term blood transfusions, such as those with thalassemia, sickle cell anemia, or other chronic anemias. It works by binding to excess iron, facilitating its excretion from the body.
Uses
Deferasirox is primarily used to treat chronic iron overload in patients undergoing repeated blood transfusions. It is indicated for:
- Transfusional iron overload due to thalassemia, sickle cell disease, or other anemias.
- Non-transfusion-dependent thalassemia (NTDT) with iron overload.
| Brand Name | Deferasirox |
|---|---|
| Type | |
| Weight | |
| Generic | Deferasirox |
| Manufacturer | |
| Available in | English বাংলা |
Mechanism of Action
Deferasirox binds to excess iron in the bloodstream, forming a complex that is excreted through the bile and urine. It selectively binds to ferric iron (Fe3+), preventing the accumulation of toxic levels of free iron, which can damage organs through oxidative stress.
How Long Does It Take to Work?
The effects of Deferasirox on reducing iron levels can be seen within several weeks, though optimal results often require several months of treatment. Regular monitoring of iron levels is necessary to assess efficacy and adjust dosage.
Absorption
Deferasirox is rapidly absorbed after oral administration, with peak plasma concentrations achieved within 1.5 to 4 hours. Absorption may be affected by food, particularly high-fat meals, which can increase its bioavailability.
Route of Elimination
Deferasirox and its iron complexes are primarily eliminated via the feces (approximately 84%), with a smaller percentage excreted through urine (around 8%).
Dosage
The drug should be started after the transfusion of approximately 20 units (about 100 ml/kg) of packed red blood cells or evidence of chronic iron overload is present (e.g. serum ferritin >1,000 microgram/L).The recommended initial daily dose of Deferasirox is 20-40 mg/kg body weight per day in empty stomach preferably half an hour before breakfast. The tablets are dispersed by stirring in a glass of water or apple or orange juice (100 to 200 ml) until a fine suspension is obtained. After the suspension has been swallowed, any residue must be re-suspended in a small volume of water or juice and swallowed, The tablets must not be chewed or swallowed whole. Dispersion in carbonated drinks or milk is not recommended due to foaming and slow dispersion, respectively.
Serum ferritin to be monitored every month and the dose is adjusted accordingly every 3 to 6 months based on the trends in serum ferritin. If iron overload is inadequately controlled, doses of up to 40 mg/kg may be considered. If serum ferritin level is controlled, dose reductions in steps of 5 to 10 mg/kg should be considered to maintain serum ferritin at 500 microgram/l. Dose interruption can be done if sustained control is achieved,
The recommended starting dose of Deferasirox depends on the patient’s body weight and the degree of iron overload. The following dosage guidelines apply:
- Transfusional Iron Overload: 20 mg/kg once daily, taken on an empty stomach. The dose may be adjusted based on serum ferritin levels and tolerability.
- Non-transfusion-dependent thalassemia: 10 mg/kg daily. This can be increased up to 20 mg/kg if necessary, based on serum ferritin levels.
Administration
Deferasirox is administered orally once daily, preferably on an empty stomach at least 30 minutes before food. It can be dissolved in water, apple juice, or orange juice for easier administration.
Side Effects
Common side effects include:
- Abdominal pain
- Nausea
- Diarrhea
- Skin rash
- Renal toxicity (elevated creatinine)
- Hepatic toxicity
- Hearing loss
- Vision disturbances
Toxicity
In cases of overdose, the most common toxic effects are gastrointestinal disturbances such as nausea, vomiting, and diarrhea. Severe cases may result in renal or hepatic impairment. Treatment of overdose may require symptomatic and supportive measures.
Precautions
Patients with renal or hepatic impairment should use Deferasirox with caution, as the drug may exacerbate these conditions. Regular monitoring of kidney and liver function is essential during treatment.
Interaction
Deferasirox interacts with:
- Antacids containing aluminum, as these may reduce its efficacy.
- Nonsteroidal anti-inflammatory drugs (NSAIDs), as they can increase the risk of kidney damage.
- Warfarin, as it may increase the risk of bleeding.
Disease Interaction
Deferasirox should be used cautiously in patients with renal or hepatic impairment, as well as in those with severe anemia not related to iron overload.
Drug Interaction
Potential interactions include:
- CYP3A4 inhibitors (e.g., ketoconazole), which may increase Deferasirox levels.
- Rifampin, which may reduce Deferasirox efficacy by inducing its metabolism.
- Diuretics, which may exacerbate renal toxicity when used with Deferasirox .
Food Interactions
Food, especially high-fat meals, can increase the absorption of Deferasirox . It is generally recommended to take the drug on an empty stomach to ensure consistent absorption.
Pregnancy Use
There are no adequate and well-controlled studies of Deferasirox in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactation Use
It is unknown whether Deferasirox is excreted in human milk. Breastfeeding should be discontinued during treatment to avoid potential harm to the infant.
Acute Overdose
Acute overdose of Deferasirox may cause gastrointestinal disturbances (nausea, vomiting, diarrhea) and renal or hepatic toxicity. In case of overdose, symptomatic treatment and monitoring of kidney and liver function are recommended.
Contraindication
Deferasirox is contraindicated in patients with:
- Severe renal impairment (creatinine clearance < 40 mL/min).
- Severe hepatic impairment.
- Known hypersensitivity to Deferasirox or any of its components.
Use Direction
Deferasirox should be taken once daily on an empty stomach or with a light meal. The tablets should be dispersed in water, apple juice, or orange juice before administration, and the dose should be adjusted based on iron levels and kidney/liver function.
Storage Conditions
Store Deferasirox tablets at room temperature (20-25°C) in a dry place, away from moisture and heat.
Volume of Distribution
The volume of distribution of Deferasirox is approximately 14 L, indicating moderate distribution into body tissues.
Half-Life
The half-life of Deferasirox is approximately 8 to 16 hours, depending on the dose and patient’s metabolic status.
Clearance
Deferasirox is primarily cleared via the hepatobiliary system, with elimination through feces. Its clearance is reduced in patients with hepatic impairment.
See in details version Deferasirox also Deferasirox in bangla
