Desferrioxamine

#complete #carded

Related FACEM curriculum (2022) learning objectives:

• ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
• ME 3.8.2.4 Identify the appropriate antidote or antivenom.

Presentations

• Desferrioxamine mesylate:
  • 500 mg vials (powder for reconstitution).
  • 2 g vials (powder for reconstitution).

Toxicological Indications

• Acute iron poisoning:
  • Systemic iron toxicity (severe gastroenteritis, shock, metabolic acidosis, altered mental state).
  • High risk of systemic toxicity (serum iron >90 micromol/L or 500 microgram/dL at 4–6 hours post-ingestion).
• Chronic iron overload.

Contraindications

• None.

Mechanism of Action

• Binds ferric ion (Fe³⁺) in plasma, forming ferrioxamine, a stable, water-soluble complex excreted in urine.
• Removes iron from transferrin and haemosiderin but not intracellularly.
• 1000 mg of DFO binds 85 mg of ferric iron.

Pharmacokinetics

• Volume of distribution: 1 L/kg; minimal tissue penetration.
• Steady-state concentration achieved at 6–12 hours of IV infusion.
• Hepatically metabolised with some unchanged excretion in urine.
• Elimination half-life: 3 hours (prolonged in renal failure).
• Ferrioxamine: smaller volume of distribution, not metabolised, excreted unchanged in urine, dialysable.

Administration

General

• Mandatory cardiac monitoring.
• Reconstitute 500 mg with 5 mL sterile water; dilute in 100 mL saline or 5% dextrose.

Dosage

• Initial IV infusion: 15 mg/kg/hour.
• Increase rate up to 40 mg/kg/hour in life-threatening toxicity (monitor for hypotension).
• Avoid infusion >24 hours.

Therapeutic Endpoints

• Clinical stability.
• Serum iron <60 micromol/L (350 microgram/dL).

Adverse Drug Reactions

• Hypersensitivity reactions.
• Hypotension (reduce infusion rate if rapid/high-dose infusion causes this).
• Prolonged infusion (>24 hours): risk of ARDS.
• Toxic retinopathy.
• Secondary infections (e.g., Yersinia sepsis, mucormycosis) due to ferrioxamine acting as a siderophore.

Specific Considerations

• Pregnancy: Safe to use in severe iron poisoning; no known teratogenicity.
• Paediatrics: Same dosage as adults.

Handy Tips

• Administer DFO before intracellular iron uptake to prevent systemic toxicity.
• Intramuscular DFO not suitable for acute iron poisoning.
• Urine discolouration to "vin rosé" is unreliable as an indicator of effective chelation.
• DFO chelation is rarely needed beyond 6–24 hours.

Pitfalls

• Unnecessary DFO administration.
• Excessive duration of therapy.

Controversies

• Lack of controlled trials or dose–response studies on DFO efficacy in human iron poisoning.
• Uncertainty regarding optimal indications, dosing, administration route, and therapeutic endpoints.