Deferasirox

Deferasirox is an oral iron chelator used for chronic iron overload from transfusions and for non-transfusion-dependent thalassaemia. It is taken once daily and binds iron in a 2 to 1 ratio, with excretion in faeces.

Classification. Iron chelator.

Mechanism. Binds ferric iron from the plasma and tissues, forming a stable complex that is eliminated mainly in bile and faeces.

Pharmacokinetics. Absorption is about 70% of the oral dose, with peak levels at 1.5 to 4 hours. It is more than 99% protein bound and cleared by glucuronidation, with half-life 8 to 16 hours. Bioavailability differs between the film-coated and dispersible tablets, so doses are not interchangeable.

Chronic transfusional iron overload (age 2 years and over; ferritin persistently over 1000 µg/L after about 20 units, or liver iron over 7 mg/g dry weight).

• Film-coated tablets: start 14 mg/kg orally once daily; adjust in steps of 3.5 to 7 mg/kg every 3 to 6 months by ferritin trend; maximum 28 mg/kg daily.
• Dispersible tablets: start 20 mg/kg once daily; adjust in steps of 5 to 10 mg/kg every 3 to 6 months; maximum 40 mg/kg daily.
• Loading dose: none. Maintenance: the dose that keeps ferritin in the target range (usually under 1000 µg/L, and under 500 µg/L in heart iron overload).

Non-transfusion-dependent thalassaemia (age 10 years and over; liver iron 5 mg/g dry weight or more, or ferritin over 300 µg/L).

• Film-coated: 7 mg/kg once daily, maximum 14 mg/kg. Dispersible: 10 mg/kg once daily, maximum 20 mg/kg.
• Stop when liver iron falls under 3 mg/g dry weight.

Dose modification. If creatinine rises to more than 133% of baseline on two occasions, reduce the daily dose by 7 to 10 mg/kg (dispersible) or 3.5 to 7 mg/kg (film-coated). Interrupt when ferritin is under 500 µg/L (transfusional) or persistent kidney, liver or marrow toxicity.

Adjustments. Kidney: eGFR 40 to 60 mL/min/1.73 m², reduce the starting dose by 50%; contraindicated below 40. Liver: Child-Pugh B, reduce the starting dose by 50%; avoid in Child-Pugh C. Weight: dose by weight.

Contraindications. eGFR under 40 mL/min/1.73 m², platelets under 50 × 10⁹/L, high-risk myelodysplasia, advanced malignancy, hypersensitivity.

Boxed-warning-level risk. Acute kidney injury and renal failure, hepatic failure, and gastrointestinal haemorrhage, with higher risk in older adults, advanced disease and low platelets.

Adverse effects. Diarrhoea, nausea, vomiting, abdominal pain, rash, raised creatinine, proteinuria, raised transaminases, hearing loss, lens opacity, cytopenias.

Interactions. Aluminium-containing antacids; rifampicin and other UGT inducers lower exposure; nonsteroidal anti-inflammatory drugs, corticosteroids, oral bisphosphonates and anticoagulants raise the risk of gastrointestinal bleeding; nephrotoxic agents raise renal risk. Deferasirox raises exposure of repaglinide and theophylline and may lower hormonal contraceptive effectiveness.

Pregnancy and breastfeeding. Avoid unless clearly needed; avoid breastfeeding.

Common errors. Switching between film-coated and dispersible tablets without converting the dose; skipping monthly creatinine; continuing during dehydration or diarrhoea.

Administration. Dispersible tablets: suspend in water, orange juice or apple juice and drink on an empty stomach or with a light meal; do not chew. Film-coated tablets: swallow whole with water, with or without a light meal.

Baseline. Creatinine on two occasions, eGFR, urine protein, liver function, full blood count, ferritin, audiology and eye examination.

Monitoring. Creatinine weekly for the first month and after each dose change, then monthly. Ferritin monthly. Liver function every 2 weeks in the first month then monthly. Urine protein monthly. Full blood count monthly. Audiology and eye examination yearly. Liver iron and cardiac T2* yearly.

Referral and escalation. Interrupt for acute illness with vomiting or diarrhoea, creatinine rise to over 133% of baseline, jaundice or gastrointestinal bleeding, and refer to haematology.