Deferiprone

Deferiprone is an oral iron chelator used for transfusional iron overload in thalassaemia major and other transfusion-dependent anaemias when other chelators are inadequate, and for cardiac siderosis. It is distinguished by good cardiac iron removal.

Classification. Iron chelator.

Mechanism. A bidentate ligand that binds ferric iron in a 3 to 1 ratio, crossing cell membranes, including into cardiac myocytes, and promoting renal excretion of the iron complex.

Pharmacokinetics. Rapid absorption with peak levels in 1 hour, food delays absorption. Half-life is 2 to 3 hours. It is metabolised by glucuronidation (UGT1A6) and excreted in urine as the inactive glucuronide, which colours urine red-brown.

Transfusional iron overload (age 6 years and over; some labels from 3 years).

• Dose: 75 mg/kg daily, in three divided doses (25 mg/kg three times daily). The twice-daily extended formulation is dosed separately by the label.
• Titration: increase to a maximum of 100 mg/kg daily if the response is inadequate, judged from ferritin and cardiac iron.
• Maximum: 100 mg/kg daily. Loading dose: none. Maintenance: the lowest dose that keeps iron in range.
• Combination with deferoxamine: for cardiac iron overload or resistant overload, with weekly neutrophil monitoring.

Adjustments. Kidney: no adjustment in mild to moderate impairment; limited data when eGFR is under 30 mL/min. Liver: no adjustment; monitor alanine aminotransferase, stopping for persistent rises. Age: use in children from 6 years is regionally licensed.

Contraindications. A history of neutropenia or agranulocytosis, concurrent drugs that cause neutropenia (for example clozapine), pregnancy, breastfeeding, hypersensitivity.

Boxed-warning-level risk. Agranulocytosis (neutrophils under 0.5 × 10⁹/L) and neutropenia, which can lead to serious infection and death.

Adverse effects. Nausea, vomiting, abdominal pain, arthralgia, raised alanine aminotransferase, zinc deficiency, red-brown urine, appetite increase, neutropenia.

Interactions. Polyvalent cations (iron, zinc, aluminium antacids) are separated by at least 4 hours. UGT1A6 inhibitors (diclofenac, probenecid, paracetamol) may raise exposure. Drugs that cause neutropenia are avoided.

Pregnancy and breastfeeding. Contraindicated; teratogenic in animals. Women of childbearing age need effective contraception.

Regional points. Weekly blood counts are the main barrier in East Africa; use only where they can be done reliably and results reach a prescriber the same week.

Common errors. Missing weekly counts; continuing through fever; confusing the immediate and extended-release formulations.

Administration. Oral, three times daily with food to limit nausea. Separate from antacids and mineral supplements by 4 hours.

Baseline. Full blood count with absolute neutrophil count (over 1.5 × 10⁹/L before starting), liver function, zinc, ferritin, cardiac T2* and liver iron, pregnancy test.

Monitoring. Absolute neutrophil count weekly. Interrupt if neutrophils fall under 1.5 × 10⁹/L; stop if under 0.5 × 10⁹/L, which is agranulocytosis. Alanine aminotransferase every 2 months. Ferritin every 3 months. Cardiac T2* and liver iron yearly. Zinc yearly.

Referral and escalation. Any fever, sore throat or mouth ulcer needs a same-day blood count and drug interruption. Neutropenia needs haematology review and empirical antibiotic cover.