Deferoxamine

Deferoxamine is a parenteral iron chelator, used for chronic transfusional iron overload and for acute iron poisoning. It binds ferric iron in a 1 to 1 ratio and the complex (ferrioxamine) is excreted in urine and bile.

Classification. Iron chelator.

Mechanism. Chelates free and weakly bound iron, including from ferritin and haemosiderin, but not from transferrin or haemoglobin. Urine turns orange-red (vin rosé) when iron is excreted.

Pharmacokinetics. Oral absorption is poor. Subcutaneous and intramuscular absorption is good. Plasma half-life is about 6 hours for the parent drug, so prolonged infusion is needed for chronic overload. About 55% of an administered dose is excreted in urine and the rest in bile.

Chronic transfusional iron overload (start after 10 to 20 transfusions or when ferritin is 1000 µg/L or more).

• Dose: 20 to 60 mg/kg daily by subcutaneous infusion over 8 to 12 hours, 5 to 7 nights each week, using a portable pump. Adults commonly use 40 mg/kg.
• Children: 20 to 40 mg/kg daily, kept below 40 mg/kg until growth is complete, to avoid growth impairment. Start after age 3 years where possible.
• Maximum: 60 mg/kg daily (adults). Keep the mean daily dose in mg/kg divided by serum ferritin in µg/L under 0.025.
• Intensive therapy for cardiac iron overload or heart failure: 50 to 60 mg/kg daily as a continuous 24 hour intravenous infusion by central line, in specialist units, usually with deferiprone.
• Vitamin C: 100 to 200 mg orally daily on infusion days in adults, given after the first month and not in heart failure.

Acute iron poisoning (adults and children).

• Indications: serum iron over 500 µg/dL (90 µmol/L), or symptoms such as shock, acidosis, coma or seizures, or a large ingestion.
• Dose: 15 mg/kg every hour by continuous intravenous infusion; maximum 80 mg/kg in 24 hours (6 g in adults). Intramuscular dosing is an alternative if there is no intravenous access: 1 g initially, then 500 mg every 4 to 12 hours.
• Duration: stop when the patient is clinically well, acidosis is corrected and urine is no longer orange-red, usually within 24 hours. Prolonged infusion beyond 24 hours raises the risk of acute respiratory distress syndrome.

Adjustments. Kidney: reduce or avoid in severe impairment, as ferrioxamine is cleared by the kidney and the drug is contraindicated in anuria. Liver: no adjustment. Pregnancy: avoid, especially in the first trimester, unless life-threatening iron toxicity.

Contraindications. Hypersensitivity; severe renal disease or anuria (except in acute poisoning with dialysis available).

Adverse effects. Common: injection-site pain, induration, erythema and itching. Serious: high-frequency hearing loss, retinal and optic neuropathy, growth retardation with high doses in children, bone dysplasia, hypotension with rapid intravenous infusion, pulmonary toxicity (acute respiratory distress syndrome), renal impairment, allergy. Yersinia enterocolitica and mucormycosis infections are more frequent with iron chelation; stop deferoxamine during febrile illness and treat the infection.

Interactions. Vitamin C in cardiac dysfunction can impair left ventricular function. Prochlorperazine may cause loss of consciousness. Gallium-67 imaging is affected.

Pregnancy and breastfeeding. Avoid except for life-threatening poisoning. Avoid breastfeeding.

Regional points. In East Africa deferoxamine is the most widely available chelator for thalassaemia major, and the pump or syringe driver is often the limiting factor. Iron poisoning in children from adult iron tablets is a common presentation.

Common errors. Rapid intravenous bolus; high doses in young children; continuing during sepsis; omitting audiology and eye examinations.

Preparation. For subcutaneous use, dissolve 500 mg in 5 mL sterile water (100 mg/mL) and infuse through a butterfly needle in the abdomen, thigh or arm. For intravenous use, dilute in 0.9% sodium chloride or 5% glucose; do not exceed 15 mg/kg/hour. Do not refrigerate the reconstituted solution; discard it if cloudy.

Baseline. Ferritin, full blood count, creatinine, liver function, audiology, eye examination and growth chart; cardiac and liver iron by magnetic resonance imaging where available.

Monitoring. Ferritin every 3 months. Audiology and ophthalmology yearly. Growth in children every 6 months. Cardiac T2* and liver iron concentration every 1 to 2 years. In poisoning: serum iron, bicarbonate or pH, urine colour, blood pressure and creatinine.

Referral and escalation. Refer for hearing or visual change, falling ferritin below 500 µg/L (reduce dose), poor adherence, or cardiac iron overload, which needs intensive chelation.