Deferoxamine uses, brand name, injection and its doses

Description of  Deferoxamine 

Deferoxamine is an iron-chelating agent used in the treatment of acute iron intoxication and chronic iron overload secondary to multiple RBC transfusions (i.e., transfusional iron overload) in patients requiring multiple RBC transfusions such as those with thalassemia, sickle cell anemia, or other chronic anemias. Initially produced as a ferric compound, the drug has the iron component chemically removed, resulting in an iron-free ligand. This ligand is then used to bind excess ferric ions in cases of iron poisoning or iron overload associated with transfusion-dependent anemia. Deferoxamine can be used to remove iron in patients with primary hemochromatosis, but phlebotomy is generally preferred for this condition. Deferoxamine also chelates aluminum and increases its renal clearance, and the drug can be used as a diagnostic test for aluminum overload. Deferoxamine was approved by the FDA in 1968.

Mechanism of Action of Deferoxamine

Ferric ions bind to the 3 hydroxamic groups of deferoxamine, creating ferrioxamine, a stable, water-soluble complex that is then readily excreted by the kidneys. Deferoxamine’s affinity for iron is greater than that of other chelating agents, and administration of the drug does not appear to increase the excretion of electrolytes or other trace minerals. Deferoxamine extracts iron most readily from iron stores in which the bonds are relatively weak (i.e., ferritin, hemosiderin, and transferrin) and does not appear to chelate iron from the more tightly bound stores such as hemoglobin or the cytochromes.

One gram of deferoxamine has the potential to combine with 85 mg of iron, but the rate of iron excreted is dependent on pH, occurring most readily at an acidic pH. Deferoxamine complexes preferentially, if not exclusively, with the ferric ion. Concomitant administration of ascorbic acid with deferoxamine may increase the excretion of iron by promoting the conversion of ferrous ions to ferric ions. While enhancement of the renal elimination of iron is believed to be the predominant action of deferoxamine, some believe that deferoxamine may exert protective actions at the cellular level. The chelation of deferoxamine (and its subsequent conversion to ferrioxamine) may limit iron entry into cells because ferrioxamine is less permeable than deferoxamine. It is also possible that deferoxamine chelates intracellular extramitochondrial iron. Aluminum excretion by the kidneys is also increased by deferoxamine. Deferoxamine has a low affinity for calcium.

Pharmacokinetics

Deferoxamine most commonly is administered parenterally, but it has been administered orally in an attempt to bind with iron in the gut and prevent its absorption.

Ferrioxamine, the deferoxamine-iron complex, is water-soluble and thus distributes mainly into the extracellular space, while deferoxamine distributes throughout the body. Deferoxamine is rapidly metabolized to inactive products in the plasma and by other tissues. After IV administration to nephrectomized dogs, the half-life is roughly 1 hour. Ferrioxamine is slowly metabolized and is eliminated unchanged in the urine. The ferrioxamine complexes impart a characteristic orange-red color to the urine. Iron excretion is maximal during the initial therapy, indicating that only the more accessible iron stores are removed. Approximately one-third of the iron eliminated in response to deferoxamine therapy is excreted in the feces. The elimination half-life of deferoxamine is 6 hours.

Route-Specific Pharmacokinetics
Oral Route
Deferoxamine is poorly absorbed across the GI tract, although ferrioxamine (i.e., the deferoxamine-iron complex) can be absorbed to a limited extent. Because iron is less readily complexed in an acidic environment, the oral use of deferoxamine is controversial.

• Deferoxamine Mesylate

• Desferal

• Heavy Metal Chelator

• Iron toxicity, acute: Adult
• Iron toxicity, acute: Pediatric: yes (3 years or older)
• Iron toxicity, chronic, Due to transfusion-dependent anemias: Adult
• Iron toxicity, chronic, Due to transfusion-dependent anemias: Pediatric: yes (3 years or older)

• Dermatologic: Injection site pain
• Endocrine metabolic: Decreased body growth

• Cardiovascular: Cardiac complication, Hypotension, Shock, Tachyarrhythmia
• Hematologic: Aplastic anemia, Thrombocytopenia
• Immunologic: Hypersensitivity reaction (frequent)
• Ophthalmic: Abnormal vision
• Otic: Auditory dysfunction
• Renal: Acute renal failure
• Other: Mucormycosis (rare)

• Vials are for single use only because reconstituted with sterile water for injection; discard unused portions and do not refrigerate
• If reconstituted under validated aseptic conditions, the reconstituted vial can be stored at room temperature for a maximum of 24 hours
• Administer immediately following reconstitution; commence treatment within 3 hours
• Administer IM or by slow subQ or slow IV infusion; do not use rapid IV injection (can cause a severe injection reaction)
• Do not administer concurrently with blood transfusion; may give prior to or following same-day blood transfusion
• Intramuscular: reconstitute 500-mg vial with 2 mL of sterile water for injection; yields a 213 mg/mL final concentration
• Intramuscular: reconstitute 2-g vial with 8 mL of sterile water for injection; yields a 213 mg/mL final concentration
• Intramuscular: (acute iron intoxication) IM administration is preferred and should be used for all patients not in shock
• Intravenous: do not administer via rapid IV injection (can cause a severe injection reaction)
• Intravenous: (acute iron intoxication) route should only be used in patients with cardiovascular collapse and then only by slow infusion .
• Intravenous: reconstitute 500-mg vial with 5 mL of sterile water for injection; yields a 95 mg/mL final concentration
• Intravenous: reconstitute 2-g vial with 20 mL of sterile water for injection; yields a 95 mg/mL final concentration
• Intravenous: (acute iron intoxication) further dilute reconstituted solution in NS, 0.45% NaCl, glucose in water, or Ringer lactate solution
• Intravenous: (acute iron intoxication) infusion rate should not exceed 15 mg/kg/hr for the first 1000 mg administered; subsequent IV dosing, if required, must be at a slower rate not to exceed 125 mg/hr
• Intravenous: (acute iron intoxication) discontinue IV and switch to IM administration as soon as clinically possible
• Subcutaneous: reconstitute 500-mg vial with 5 mL of sterile water for injection; yields a 95 mg/mL final concentration
• Subcutaneous: reconstitute 2-g vial with 20 mL of sterile water for injection; yields a 95 mg/mL final concentration
• Subcutaneous: use a small portable pump capable of providing a continuous mini-infusion to administer a dose over 8 to 24 hours

• Desferal: Injection Powder for Solution: 500 MG

• Injection Powder for Solution: 2 GM, 500 MG

• Important Note: Orphan drug designation: Treatment of chronic iron overload resulting from conventional transfusional treatment of beta-thalassemia major and sickle cell anemia
• Important Note: Orphan drug designation: Treatment of acute iron poisoning
• Important Note: Orphan drug designation: Treatment of sickle cell leg ulcers
• Iron toxicity, acute: 15 mg/kg/hr continuous IV infusion; may titrate up to 40 mg/kg/hr in patients with life-threatening iron toxicity; infuse for 12 hours with moderate poisoning or for up to 24 hours with severe poisoning (literature dosing)
• Iron toxicity, acute: (all patients not in shock) 1 g IM initially, then 500 mg IM every 4 hours for 2 doses, then subsequent doses of 500 mg every 4 to 12 hours as needed; MAX 6 g/day (manufacturer dosing)
• Iron toxicity, acute: (patients in cardiovascular collapse) 1 g IV initially at a MAX rate of 15 mg/kg/hr, then 500 mg IV over 4 hours for 2 doses, then subsequent doses of 500 mg IV over 4 to 12 hours as needed; MAX rate for subsequent infusions 125 mg/hr; MAX dose 6 g/day (manufacturer dosing)
• Iron toxicity, chronic, Due to transfusion-dependent anemias: 0.5 to 1 g IM daily; MAX dose 1 g/day
• Iron toxicity, chronic, Due to transfusion-dependent anemias: 1 to 2 g (20 to 40 mg/kg/day) slow SUBQ infusion over 8 to 24 hours; some patients may excrete as much iron after a shorter infusion of 8 to 12 hours
• Iron toxicity, chronic, Due to transfusion-dependent anemias: 40 to 50 mg/kg/day slow IV infusion over 8 to 12 hours for 5 to 7 days/week; average doses should not exceed MAX 60 mg/kg/day; MAX rate 15 mg/kg/hr

• Important Note: Orphan drug designation: Treatment of chronic iron overload resulting from conventional transfusional treatment of beta-thalassemia major and sickle cell anemia
• Important Note: Orphan drug designation: Treatment of acute iron poisoning
• Important Note: Orphan drug designation: Treatment of sickle cell leg ulcers
• General Dosage Information: safety and effectiveness have not been determined in pediatric patients younger than 3 years
• Iron toxicity, acute: 50 mg/kg/dose IM every 6 hours until resolution of systemic toxicity ; MAX 6 g/day
• Iron toxicity, acute: 15 mg/kg/hr IV as a continuous infusion ; may titrate up to 35 mg/kg/hr for life-threatening iron toxicity ; infuse for 12 hours with moderate poisoning or for up to 24 hours with severe poisoning (literature dosing)
• Iron toxicity, acute: initial IV rate not to exceed 15 mg/kg/hr, subsequent infusions MAX rate 125 mg/hr; MAX dose 6 g/day
• Iron toxicity, chronic, Due to transfusion-dependent anemias: (3 years or older) 20 to 40 mg/kg/day slow IV infusion; average dose should not exceed MAX 40 mg/kg/day until growth has stopped; MAX IV rate 15 mg/kg/hr