Deferoxamine

Indications

Deferoxamine is used for: Acute Iron Poisoning, Chronic Iron Overload

Adult Dose

Acute Iron Poisoning IM administration is indicated for all patients NOT in shock; administer 1g IM initially and then 500mg Q4hr for 2 doses Depending upon clinical response, subsequent doses of 500mg Q4-12hr can be administered Maximum dose: 6g in 24 hours IV administration should be reserved for patients in a state of cardiovascular collapse or shock; 1g slow IV infusion Rate of infusion should not exceed 15mg/kg/hr for the first dose; subsequent doses should not be infused at a faster rate than 125mg/hr Chronic Iron Overload SC administration: 1-2g (20-40mg/kg/day) SC over 8-24 hours using a small portable pump capable of providing continuous mini-infusion; individualize infusion duration IV administration in patients with IV access: 40-50mg/kg/day over 8-12 hours for 5-7 days/ week (maximum of < 60mg/kg/day and an IV infusion rate of <15mg/kg/hr) IM administration: 0.5-1g QD (maximum of 1g QD)

Child Dose

Acute Iron Poisoning <3 years: Safety and effectiveness has not been established >3 years: Administer 1g IM initially and then 500mg Q4hr for 2 doses for all patients not in shock Depending upon clinical response, subsequent doses of 500mg Q4-12hr can be administered; maximum dose: 6g in 24 hours IV administration should be reserved for patients in a state of cardiovascular collapse or shock; 1g slow IV infusion Rate of infusion should not exceed 15mg/kg/hr for the first dose; subsequent doses should not be infused at a faster rate than 125mg/hr 20 mg/kg IM (for all patients not in shock) or IV (only if patient in cardiovascular collapse/shock); then, 10 mg/kg IM/IV q4hr x2; then, depending on clinical circumstance, may administer addtional doses of 10 mg/kg IM/IV q4-12hr PRN IV infusion rate: Initial 1 g at 15 mg/kg/hr, all subsequent doses no more than 125 mg/hr No more than 6 g/day (IM/IV), but in severe cases should continue infusion up to 24 hours Chronic Iron Overload <3 years: Safety and effectiveness has not been established >3 years: 0.5-1g IM QD (maximum of 1g QD) SC administration: 1-2g (20-40mg/kg/day) SC over 8-24 hours using a small portable pump capable of providing continuous mini-infusion; individualize infusion duration IV administration in patients with IV access: 40-50mg/kg/day over 8-12 hours for 5-7 days/ week (maximum of < 60mg/kg/day and an IV infusion rate of <15mg/kg/hr)

Renal Dose

Administration

Reconstitution Preparation for IM administration: 500mg with 2mL SWI/ 2g with 8mL SWI (final concentration after reconstitution for both: 213mg/mL) Preparation for IV administration: 500mg with 5mL SWI/ 2g with 20mL SWI (final concentration after reconstitution for both: 95mg/mL) Preparation for SC administration: 500mg with 5mL SWI/ 2g with 20mL SWI (final concentration after reconstitution for both: 95mg/mL) Use immediately; ? 3hours of reconstitution When reconstitution is carried under aseptic conditions, may store ? 24 hr at 25°C; do not refrigerate; do not reconstitute with other solvents or under different conditions due to risk of precipitation

Contra Indications

Known hypersensitivity to deferoxamine or any of its components Patients with severe renal disease or anuria

Precautions

Administration by rapid IV injection may cause flushing of the skin, urticaria, hypotension, and shock; administer IM or by slow SC or IV infusion Rare fatal cases of mucormycosis have been reported; if any signs and symptoms occur, discontinue treatment and conduct mycological tests immediately Severe chronic iron overload may precipitate reversible cardiac function impairment if high doses of Vitamin C (> 500 mg QD in adults) are given concomitantly; do not administer Vitamin C to HF patients; wait > 1 month after treatment to begin supplemental Vitamin C therapy; administer vitamin C only if the patient is receiving Desferal regularly, ideally soon after setting up the infusion pump; do not exceed a daily vitamin C dose of 200 mg in adults, given in divided doses; monitor cardiac function closely during such combined therapy Dialysis patients with aluminum-related encephalopathy may experience neurological dysfunction (seizures), possibly due to an acute increase in circulating aluminum;onset of dialysis dementia may be precipitated; treatment in the presence of aluminum overload may result in decreased serum calcium and aggravation of hyperparathyroidism Monitor for changes in renal function Not a substitute for standard measures generally used in iron toxicity (eg, induced emesis, gastric lavage) Iron overload increases susceptibility of patients to Yersinia enterocolitica and Yersinia pseudotuberculosis infections; treatment may therefpre enhance patient's susceptibility Monitor pediatric patients for body weight and growth every 3 months

Pregnancy-Lactation

Pregnancy Category: C Lactation: Unknown if excreted in breast milk, use caution

Interactions

Adverse Effects

Side effects of Deferoxamine : Frequency Not Defined Injection site reactions (eg, localized irritation, induration, infiltration, pain, erythema, wheal formation, eschar, burning, swelling, pruritus, crust, vesicles, local edema); these may be associated with systemic allergic reactions Systemic reactions (eg, abdominal pain, arthralgia, asthma, fever, headache, myalgia, nausea, vomiting) Cardiovascular reactions (eg, hypotension with too rapid IV infusion, tachycardia, shock) Hypersensitivity reactions (eg, anaphylactic reaction with or without shock, angioedema, generalized rash, urticaria) Digestive reactions (eg, abdominal discomfort, diarrhea, nausea, vomiting) Hematologic reactions (eg, blood dyscrasia including thrombocytopenia and leucopenia) Hepatic reactions (eg, increased transaminases, hepatic dysfunction) Musculoskeletal reactions (eg, muscle spasms, growth retardation and bone changes including metaphyseal dysplasia are common in doses ≥ 60 mg/kg, especially those who begin iron chelation in the first three years of life; reduced risk if doses are kept to ≤ 40 mg/kg) Nervous System reactions (eg, neurological disturbances including dizziness, peripheral sensory, motor, or mixed neuropathy, paresthesias, seizures; exacerbation or precipitation of aluminum-related dialysis encephalopathy) Special Senses reactions (eg, high-frequency sensorineural hearing loss and/or tinnitus are uncommon if dosage guidelines are not exceeded and if dose is reduced when ferritin levels decline; visual disturbances inlcuding decreased acuity, blurred vision, loss of vision, dyschromatopsia, night blindness, visual field defects, scotoma, retinopathy (pigmentary degeneration), optic neuritis, and cataracts are rare if dosage guidelines are not exceeded) Respiratory reactions (eg, acute respiratory distress syndrome with dyspnea, cyanosis, and/or interstitial infiltrates) Very rare generalized rash Urogenital reactions including dysuria, acute renal failure, increased serum creatinine and renal tubular disorders

Mechanism of Action

Desferal chelates iron by forming a stable complex that prevents the iron from entering into further chemical reactions; also chelates iron readily from ferritin and hemosiderin but not readily from transferrin; does not combine with the iron from cytochromes and hemoglobin; chelate is readily soluble and is renally excreted