Introduction
Deferasirox is an iron chelator and chronic iron overload in patients receiving long term blood transfusions.
Uses
Deferasirox is an iron chelator used to treat chronic iron overload caused by blood transfusions. Also used in patients with non-transfusion-dependent thalassemia syndromes, and in patients with elevated liver iron concentration and serum ferritin.
For the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older.
Associated Conditions
Pharmacodynamics
Deferasirox is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain.
Mechanism of Action
Two molecules of deferasirox are capable of binding to 1 atom of iron. Deferasirox works in treating iron toxicity by binding trivalent (ferric) iron (for which it has a strong affinity), forming a stable complex which is eliminated via the kidneys.
Absorption
The absolute bioavailability (AUC) of deferasirox tablets for oral suspension is 70% compared to an intravenous dose.
Volume of Distribution
- 14.37 ± 2.69 L
Protein Binding
Deferasirox is highly (~99%) protein bound almost exclusively to serum albumin.
Route of Elimination
Deferasirox and metabolites are primarily (84% of the dose) excreted in the feces. Renal excretion of deferasirox and metabolites is minimal (8% of the administered dose).
Half Life
The mean elimination half-life ranged from 8 to 16 hours following oral administration.
Food Interactions
- Take at the same time every day.
- Take on an empty stomach. Take at least 30 minutes before food.
- Take separate from meals. Administration with food causes inconsistent bioavailability. May administer granules with a light meal, if necessary.
Dosage
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,
