Deferasirox is used to treat chronic iron overload caused by repeated blood transfusions in adults and children aged 2 years and older who have thalassaemia, sickle cell disease, or myelodysplastic syndrome. It is also indicated for managing chronic iron overload in patients aged 10 years and above with non–transfusion-dependent thalassaemia syndromes.

Deferasirox is an orally active iron chelator with high selectivity for iron. It is a tridentate ligand that binds iron strongly in a 2:1 ratio. The drug helps remove excess iron mainly through fecal excretion. It has only a low affinity for zinc and copper, so it does not lead to persistent reductions in their serum levels. In a metabolic iron balance study in iron-overloaded adult thalassaemia patients, daily doses of 10, 20, and 40 mg/kg resulted in mean net iron excretion of 0.119, 0.329, and 0.445 mg Fe/kg body weight per day, respectively.

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.

Deferasirox must be taken once daily on an empty stomach at least 30 minutes before food, preferably at the same time each day. The tablets are dispersed by stirring in a glass of water or apple or orange juice (100 to 200 mL) until a line suspension is obtained. After the suspension has been swallowed, any residue must be  resuspended 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.

Deferasirox should not be taken with aluminium-containing antacids. Caution is required when it is used together with drugs metabolized by CYP3A4 enzymes, such as cyclosporine, simvastatin, hormonal contraceptives, and midazolam. Dose adjustments may be necessary when it is co-administered with drugs like rifampicin, phenytoin, phenobarbital, or ritonavir. Possible interactions with other CYP2C8 substrates, such as paclitaxel, cannot be ruled out. Care should also be taken when used with ulcer-causing drugs like NSAIDs, corticosteroids, and oral bisphosphonates, as well as with anticoagulant medications.

Deferasirox is contraindicated in patients who are hypersensitive to the active ingredient or any of its excipients. It should not be used in patients with creatinine clearance below 40 mL/min or when serum creatinine is more than twice the upper limit of normal.

Cytopenias may occur during treatment. Gastrointestinal side effects such as diarrhea, constipation, vomiting, nausea, abdominal pain, abdominal distension, dyspepsia, and upper gastrointestinal ulceration or bleeding have been reported. Neurological effects may include headache, dizziness, and other central nervous system (CNS) involvement. Elevation of hepatic transaminases may also occur. Rare cases of Stevens-Johnson syndrome (SJS) and skin rash have been reported. Auditory and visual disturbances may also occur.

Pregnancy Category C. There are no adequate and well-controlled studies of Deferasirox in pregnant women. In animal studies, administration during pregnancy and lactation caused reduced offspring survival and an increased incidence of renal abnormalities in male offspring at exposures lower than those recommended for humans. Deferasirox should be used during pregnancy only if the expected benefit outweighs the potential risk to the fetus. It is not known whether Deferasirox is excreted in human breast milk.

Caution is advised when Deferasirox is used in combination with drugs known to have ulcerogenic or hemorrhagic risks, such as NSAIDs, corticosteroids, oral bisphosphonates, and anticoagulants. Cases of cytopenias, including agranulocytosis, neutropenia, and thrombocytopenia, have been reported; therefore, regular monitoring of blood counts is recommended during therapy. Serious hypersensitivity reactions have also been observed. If severe reactions occur, Deferasirox should be discontinued immediately and appropriate medical treatment should be started.

Pediatric use: The safety and efficacy of Deferasirox in pediatric patients are comparable to those in adults, and younger children respond similarly to older children. The recommended initial dose and dose adjustments are the same for both children and adults.

Geriatric use: Elderly patients have a higher risk of Deferasirox toxicity due to more frequent reductions in liver, kidney, or heart function, as well as the presence of other diseases or concurrent medications.

Renal impairment: Deferasirox has not been evaluated in patients with impaired kidney function.

Hepatic impairment: Deferasirox has not been studied in patients with liver impairment.

The maximum recommended dose of Deferasirox is 40 mg/kg body weight. There is no available information regarding overdose of Deferasirox.

Antidote preparations

Store in a dry place below 25°C and protect from light. Keep out of reach of children.