Deferoxamine Mesylate

Brand names Desferal, generic

Medication error Look-alike, sound-alike drug names. Deferoxamine may be confused with cefuroxime, potential deferasirox, and deferiprone. Desferal may be confused with desflurane, Desyrel, and Dexferrum.(1)

Contraindications Hypersensitivity to deferoxamine or any component of the formulation. Contraindicated and warnings in severe renal disease or anuria since both deferoxamine and the iron chelate are renally excreted.(2)

Infusion-related Flushing, urticaria, hypotension, and shock may occur, particularly with rapid IV admin- cautions istration.(2-5) Localized irritation, pain, burning, swelling, induration, infiltration, pruritus, erythema, wheal formation, eschar, crust, vesicles, and local edema.(2) Injection site reactions may be associated with systemic allergic reactions.(2) Anaphylaxis may occur.(2)

Dosage Acute iron exposure: Although the manufacturer states that IM administration is the preferred route and should be used for all patients not in shock,(2) toxicology literature supports the IV administration of deferoxamine for acute iron poisoning.(3) Continuous infusion: 15 mg/kg/hr,(3,6-9) up to 6 g/day Intermittent infusion: Initial dose of 20 mg/kg or 600 mg/m2, up to 1000 mg/ dose (IM or slow IV infusion), followed by 10 mg/kg or 300 mg/m2 q 4 hr for 2 doses Dose should be given until urine is a normal color for 24 hours(7,8) or until clinical status and laboratory values normalize. Urine may not always be a vin rosé color following administration of deferoxamine, even when iron overload is present.(37) Serum iron concentration was successfully lowered in a 7-week-old preterm (27 weeks gestational age) neonate who received 5 mg/kg/hr of deferoxamine by continuous infusion, in combination with aggressive fluid resuscitation and inotropic support. The dose could not be increased due to the development of hypotension.(11) Chronic iron overload due to transfusion-dependent anemias: Deferoxamine is FDA labeled in children >3 years of age.(2) Dose should be individualized based on the degree of iron overload. Deferoxamine is indicated in patients with sickle cell disease when transfusional iron load is >100 mg/kg and/or liver iron content in any age group exceeds 7–9 mg/g.(38) Generally, excessive liver iron content occurs when the serum fer- ritin is >3000 ng/mL.(38) Normal doses of deferoxamine range from 20–50 mg/kg/day, but doses as large as 98 mg/kg/ day over 8–12 hours have been used.(13) A recent study noted administration of 15 mg/kg/hr for 48 hours q 2 wk for a mean duration of 19.6 months to 27 patients with sickle cell disease.(15) IM or sub-Q infusions of 30–50 mg/kg for 8–12 hours every night for 5–7 nights per week have also been successfully used.(39) Aluminum-related disorders in chronic kidney disease (use not established): To avoid aluminum-induced neurotoxicity, it should not be given to patients with an initial serum aluminum >200 mcg/L. Patients should also be treated with intensive high-flux dialysis until serum aluminum is <200 mcg/L.(16) Deferoxamine test: Measure serum aluminum before infusion and 2 days later (before next dialysis session). 5 mg/kg of deferoxamine should be given during last hour of dialysis. Doses as low as 0.5 mg/kg have also been used.(16) Aluminum rise <300 mcg/L and no side effects after test: 5 mg/kg IV over last hour of hemodialysis, once per week for 2 months; high-flux hemodialysis 44 hours after dose.(16) Aluminum rise ≥300 mcg/L or side effects after test: 5 mg/kg IV over 1 hour; give 5 hours before hemodialysis, once per week for 4 months; high-flux hemodialysis after deferoxamine.(16) Hemochromatosis (neonatal) or gestational alloimmune liver disease (GALD): Patients often receive a cocktail of medications that includes deferoxamine 30 mg/kg/day infused over 8 hours until the serum ferritin is <500 mcg/L.(17) This is palliative therapy as early liver transplantation is essential for survival.  268 Deferoxamine Mesylate

Dosage adjustment Product labeling states that deferoxamine is contraindicated in patients with severe renal in organ dysfunction dysfunction or anuria because the drug and the iron chelate are renally eliminated.(2) Another reference states that therapy should continue in renal failure; however, no guide- lines were suggested for adjustment of the infusion rate.(3) One reference noted that the dose should be decreased by 25% to 50% in adults with GFR between 10 and 50 mL/min and to avoid use with GFR <10 mL/min.(18)

Maximum dosage Up to 1000 mg/dose. Although cumulative dose should not exceed 6 g/24 hr,(2) larger doses have been used in clinical practice.(3) 16 g was infused to an adult with transfusion-related iron overload over 24 hours without apparent adverse effects.(19) Although doses >50 mg/kg/day (up to 235 mg/kg/day) have been used,(12-14,20-22) doses <50–60 mg/kg/day are recommended to avoid neurotoxicity.(23) (See the Comments section.) 2520 mg or 210 mg/kg/day (15 mg/kg/hr over 14 hours) has been given safely to an 18-month-old with acute iron intoxication (serum iron concentration 447 mcg/dL).(24)

Additives None

Suitable diluents SW (for reconstitution). NS, ½NS, D5W, LR (for dilution).(2,25)

Maximum 95 mg/mL (IV) and 213 mg/mL (IM)(2) concentration

Preparation and Parenteral products should be visually inspected for particulate matter and discoloration delivery before use. Refer to appropriate references for more information on compatibility with other drugs and solutions; compatibility following Y-site delivery, and suggested stor- age and extended stability.(25) Turbid solutions should not be used.(2) Preparation: Available in 500-mg and 2-g vials of sterile drug in dry form. For IM injec- tion, reconstitute the 500-mg and 2-g vials with 2 mL and 8 mL, respectively, to yield solutions providing deferoxamine mesylate 213 mg/mL.(2,25) For IV infusion, reconstitute the 500-mg and 2-g vials with 5 mL and 20 mL, respectively, to yield solutions providing deferoxamine mesylate 95 mg/mL.(2,25) Delivery system issues: Stable at room temperature in polypropylene syringes (14 days), PVC infusion cassette reservoirs (9–17 days), and natural rubber elastomeric reservoirs (14 days).(2,25) Stability: Do not store vials above 25°C.(2) Diluents other than SW and refrigeration may cause precipitation.(25) Although reconstituted solutions may be stored for 24 hours at room temperature, the manufacturer recommends immediate use due to a lack of preservative.

IV push Not recommended.(2) (See the Infusion-Related Cautions section.)

Intermittent infusion IV should be used only for patients in cardiovascular collapse and then only by slow infu- sion.(2) The rate of infusion should not exceed 15 mg/kg/hr for the first 1000 mg adminis- tered. Subsequent IV dosing, if needed, must be at a slower rate, not to exceed 125 mg/ h r. (2) Do not exceed 15 mg/kg/hr or 125 mg/hr once the first 1000 mg has been infused.(2)

Continuous infusion Do not exceed 15 mg/kg/hr or 125 mg/hr once the first 1000 mg has been infused.(2)

Other routes of Some recommend IM administration as the preferred route for acute iron ingestion in administration patients not in shock.(2) May be given via sub-Q infusion with a portable controlled-infusion device.(25)  269