indication

For the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older.

pharmacology

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.

biotransformation

Hepatic. CYP450-catalyzed (oxidative) metabolism of deferasirox appears to be minor in humans (about 8%). Glucuronidation is the main metabolic pathway for deferasirox, with subsequent biliary excretion.

absorption

The absolute bioavailability (AUC) of deferasirox tablets for oral suspension is 70% compared to an intravenous dose.

half life

The mean elimination half-life ranged from 8 to 16 hours following oral administration.

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).

drug interactions

Aluminium: Possible physicochemical interaction

Bivalirudin: Anticoagulants increase the risk for gastrointestinal ulceration/irritation and/or GI bleeding. If these two agents must be used, patients need to be closely monitored for signs and symptoms of GI toxicity.