Deferoxamine Mesylate

Approved Indications:

• Acute Iron Poisoning (Iron Overdose):
• Treatment of acute iron intoxication in both pediatric and adult patients when serum iron levels are significantly elevated or clinical signs of toxicity are present.
• Chronic Iron Overload:
• In patients with transfusion-dependent anemias (e.g., β-thalassemia major, sickle cell anemia, myelodysplastic syndromes) who have developed chronic iron overload due to repeated blood transfusions.
• Aluminum Overload:
• Management of aluminum toxicity in patients with chronic kidney disease (CKD) on dialysis, especially when receiving aluminum-based phosphate binders or contaminated dialysis fluids.

Clinically Accepted Off-label Uses:

• Iron overload in non-transfusion-dependent anemias, when other chelators are not suitable.
• Cardiac siderosis, often in combination with other iron chelators (e.g., deferiprone).
• Neurodegenerative disorders with iron accumulation (experimental/clinical trial setting).

Route: Intravenous (IV), Subcutaneous (SC), or Intramuscular (IM) injection

Acute Iron Poisoning:

• Adults and Children:
• IV infusion: Initial dose 15 mg/kg/hour; maximum dose 80 mg/kg/day.
• Continue until serum iron falls to safe levels and symptoms resolve.

Chronic Iron Overload:

• Adults and Children >3 years:
• SC infusion via portable pump over 8–12 hours, 5–7 days/week.
• Starting dose: 20–40 mg/kg/day; adjust based on ferritin and iron burden.
• May increase up to 60 mg/kg/day in adults or 40–50 mg/kg/day in children.
• IV infusion (for severe overload or cardiac iron):
• 40–50 mg/kg/day continuously over 24 hours.

Aluminum Overload (CKD patients on dialysis):

• 5 mg/kg IV infused during the last hour of dialysis, repeated once or twice weekly.
• Also used in DFO challenge test to assess aluminum burden.

Dose Adjustments:

• Renal Impairment:
• Use with caution; risk of accumulation. Monitor iron-aluminum balance and renal function.
• Hepatic Impairment:
• No formal dose adjustment, but monitor LFTs closely.
• Elderly:
• Increased monitoring is advised due to reduced organ function.

Deferoxamine mesylate is a tridentate iron-chelating agent that binds ferric iron (Fe³⁺) with high affinity to form a stable, water-soluble complex (ferrioxamine). This complex is then excreted in urine and bile. Deferoxamine removes iron from tissue stores, including ferritin and hemosiderin, and is particularly effective at mobilizing non-transferrin-bound iron. In cases of aluminum overload, deferoxamine binds aluminum to form aluminoxamine, which is eliminated primarily via the kidneys.

Absorption:

• Poor oral bioavailability; not effective when given orally.

Distribution:

• Rapidly distributed in extracellular fluid; does not cross intact blood-brain barrier.
• Volume of distribution: ~0.25 L/kg.

Metabolism:

• Primarily hydrolyzed; minimal hepatic metabolism.

Elimination:

• Excreted mainly via kidneys (~40–60% of the iron complex is renally excreted).
• Half-life:
• Free deferoxamine: ~20 minutes
• Ferrioxamine complex: ~6 hours

Onset of Action:

• Within minutes when given IV in acute toxicity.

• Pregnancy:
• FDA Category C. Animal studies showed adverse fetal effects at high doses. Use only if clearly needed and benefits outweigh risks.
• Lactation:
• Unknown whether deferoxamine is excreted in human milk. Use caution in breastfeeding women.
• Recommendation:
• Avoid unless absolutely necessary; monitor both mother and infant if used during pregnancy or lactation.

• Primary Class: Iron chelator
• Subclass: Tridentate parenteral iron and aluminum chelating agent

• Hypersensitivity to deferoxamine or any formulation component
• Severe renal disease or anuria (especially for aluminum chelation)
• Concurrent use with prochlorperazine (risk of neurotoxicity)
• Pregnancy (in non-life-threatening conditions)

• Renal Toxicity:
• Monitor renal function closely, especially during long-term use or in CKD.
• Ocular and Auditory Toxicity:
• Reports of vision and hearing loss—perform baseline and periodic ophthalmic and audiologic exams.
• Pulmonary Complications:
• Acute respiratory distress syndrome (ARDS) reported with high IV doses—avoid rapid infusions.
• Hypotension:
• Rapid IV infusion may cause severe hypotension—infuse slowly.
• Infections (Yersinia, Klebsiella):
• Iron chelation may promote growth of certain pathogens; monitor for signs of infection.
• Neurotoxicity:
• High doses or prolonged use may cause dizziness, seizures, or neuropathy.

Common (>10%):

• Local pain, swelling, or erythema at injection site
• Fever
• Gastrointestinal upset (nausea, vomiting)

Less Common (1–10%):

• Hypotension (especially with rapid IV administration)
• Rash, urticaria
• Visual disturbances (blurred vision, retinal changes)
• Hearing loss (tinnitus, high-frequency loss)

Rare (<1%):

• Acute respiratory distress syndrome (ARDS)
• Seizures
• Anaphylaxis
• Neuropathy
• Growth retardation (with chronic high-dose use in children)

Timing:

• Injection site reactions occur early and are usually mild.
• Visual/auditory effects are dose-dependent and may be delayed.
• Neurotoxicity more common with prolonged or high-dose IV therapy.

• Prochlorperazine:
• Co-administration increases the risk of neurotoxicity (e.g., seizures, impaired consciousness); contraindicated.
• Vitamin C (Ascorbic Acid):
• May enhance iron chelation but increases risk of cardiotoxicity in iron overload; limit to ≤200 mg/day and avoid in severe cardiac iron overload.
• Nephrotoxic Drugs:
• Caution with aminoglycosides, amphotericin B, and NSAIDs due to additive renal toxicity risk.
• No significant CYP450 interactions

• 2023–2024 Guidelines from Thalassemia International Federation (TIF):
• Deferoxamine remains the standard for initial iron chelation in pediatric thalassemia patients where oral chelators are contraindicated.
• Expanded Use in Cardiac Siderosis:
• Shown to improve cardiac T2* MRI and outcomes when used in combination with oral chelators.
• FDA Updates:
• Emphasize risk of vision and hearing impairment—recommend annual screening.

• Powder for Injection (vial):
• Store at 15°C to 30°C (59°F to 86°F).
• Protect from moisture and light.
• Reconstitution:
• Reconstitute with sterile water for injection before use.
• Once reconstituted, solution is stable for 24 hours at room temperature.
• Handling Precautions:
• Use aseptic technique during preparation.
• Do not use discolored or particulate-containing solutions.
• Do Not Freeze.