Deferoxamine

Mechanism

Pharmacological Group and Molecular Target

Chelating agent for divalent and trivalent metals with high specificity for iron (Fe³⁺).

Detailed Mechanism of Action

Systemic free iron in high cellular concentrations stimulates the Fenton reaction, producing highly reactive hydroxyl free radicals that damage cell membranes, mitochondria and proteins of the liver, myocardial and pancreatic parenchyma. Deferoxamine is a bacterial sideramine purified from Streptomyces pilosus that has a flexible linear polydentate structure. It binds stoichiometrically to free ferric iron (Fe³⁺) in plasma or tissue stores of ferritin and hemosiderin to form the hydrophilic octahedral coordinated complex ferrioxamine, which lacks oxidative cellular toxicity and is passively excreted through the kidneys and bile.

Pharmacokinetics

Pharmacokinetic and Toxicokinetic Profile

• Distribution: Poor passage of intracellular membranes unless administered continuously. Very hydrophilic.
• Metabolism: Plasma enzymes partially degrade deferoxamine to inactive metabolites.
• Excretion: Renal priority for ferrioxamine (colored complex that gives urine a classic "pink vinegar" or "rosé wine" hue, qualitatively indicative of the presence and clearance of iron in the body).
• Elimination half-life: Short, between 1 and 2 hours.

Indicators and dose

Specific Clinical Indications

• Severe acute iron poisoning (accidental overdose of iron supplements in children with serum concentrations greater than 500 mcg/dL or severe gastrointestinal and systemic symptoms).
• Management of chronic iron overload syndrome secondary to repeated transfusions (hemosiderosis in thalassemia, refractory chronic anemia).

Dosage Scheme and Infusion Protocols

• Acute Iron Poisoning (Adults and Children): Continuous intravenous infusion at a rate of 15 mg/kg/hour. Avoid rapid intravenous infusion greater than 15 mg/kg/h due to the risk of massive histamine release and cardiovascular collapse due to anaphylactoid hypotension.
• Maximum Daily Dose: 6 g to 8 g in 24 hours continuously. Treatment should be continued until serum iron falls to safe levels and urine color normalizes.

Security

Contraindications and Precautions

• Severe Renal Failure (Anuria): Since ferrioxamine cannot be eliminated through the kidneys, it is contraindicated unless it is simultaneously associated with extracorporeal hemodialysis to remove the chelate formed.
• It increases the risk of severe bacterial infections due to Yersinia enterocolitica and opportunistic fungal mucormycosis, since the iron chelated by deferoxamine can be used by these pathogens as a siderophore for their own growth.