Deferoxamine Mesylate (Desferrioxamine Mesylate)

Deferoxamine Mesylate (Desferrioxamine Mesylate) is used for: Acute Iron Poisoning, Chronic Iron Overload

Acute Iron Intoxication Intramuscular Administration This route is preferred and should be used for all patients NOT in shock. A dose of 1000 mg should be administered initially. This may be followed by 500 mg every 4 hours for two doses. Depending upon the clinical response, subsequent doses of 500 mg may be administered every 4-12 hours. The total amount administered should not exceed 6000 mg in 24 hours. Intravenous Administration 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 An initial dose of 1000 mg should be administered at a rate not to exceed 15 mg/kg/hr. This may be followed by 500 mg over 4 hours for two doses. Depending upon the clinical response, subsequent doses of 500 mg may be administered over 4-12 hours. The total amount administered should not exceed 6000 mg in 24 hours. As soon as the clinical condition of the patient permits, intravenous administration should be discontinued and the drug should be administered intramuscularly. Chronic Iron Overload Subcutaneous Administration A daily dose of 1000-2000 mg (20-40 mg/kg/day) should be administered over 8-24 hours, utilizing a small portable pump capable of providing continuous mini-infusion. The duration of infusion must be individualized. In some patients, as much iron will be excreted after a short infusion of 8-12 hours as with the same dose given over 24 hours. Intravenous Administration The standard recommended method of Deferoxamine administration is via slow subcutaneous infusion over 8 – 12 hours. In patients with intravenous access, the daily dose of Deferoxamine can be administered intravenously. The standard dose is 20 – 40 mg/kg/day for children and 40–50 mg/kg/day over 8 – 12 hours in adults for 5 – 7 days per week. In adults, average doses should not exceed 60 mg/kg/day. The intravenous infusion rate should not exceed 15 mg/kg/hour. In patients who are poorly compliant, Deferoxamine may be administered prior to or following a same-day blood transfusion (for example, 1 gram over 4 hours on the day of transfusion); however, the contribution of this mode of administration to iron balance is limited. Deferoxamine should not be administered concurrently with the blood transfusion as this can lead to errors in interpreting side effects such as rash, anaphylaxis and hypotension. Intramuscular Administration A daily dose of 500-1000 mg may be administered intramuscularly. The total daily dose should not exceed 1000 mg.

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 IV infusion 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 IMPAIRMENT Use with caution.

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

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

Flushing of the skin, urticaria, hypotension, and shock have occurred when drug administered by rapid intravenous injection; best to administer IM slow SC or IV infusion Rare cases of mucormycosis, some with a fatal outcome, reported with use; if any of suspected signs or symptoms occur, discontinue treatment; mycological tests should be carried out and appropriate treatment instituted immediately Adult respiratory distress syndrome, also reported in children described following treatment with excessively high intravenous doses in patients with acute iron intoxication or thalassemia Increases in serum creatinine (possibly dose-related), acute renal failure, and renal tubular disorders, reported in postmarketing experience; monitor patients for changes in renal function Severe chronic iron overload may precipitate reversible cardiac function impairment if high doses of Vitamin C (>500 mg/day 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 deferoxamine 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 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; if it occurs, treatment should be discontinued until infection is resolved High doses and concomitant low ferritin levels associated with growth retardation; after reduction of dose, growth velocity may partially resume to pretreatment rates Ocular and auditory disturbances Ocular and auditory disturbances reported when therapy administered over prolonged periods of time, at high doses, or in patients with low ferritin levels; in most cases, both ocular and auditory disturbances were reversible upon immediate cessation of treatment MONITORING PARAMETERS Eye and ear examinations before treatment and at 3-month intervals during treatment. Monitor pediatric patients for body weight and growth every 3 months Monitor for changes in renal function

Pregnancy There are no adequate and well-controlled studies in pregnant women; administer during pregnancy only if potential benefit justifies potential risk to fetus Animal data Delayed ossification in mice and skeletal anomalies in rabbits observed after drug administered in daily doses up to 4.5 times the maximum daily human dose; no adverse effects observed in similar studies in rats Lactation Not known whether drug is excreted in human milk; because many drugs are excreted in human milk, caution should be exercised when administered to a nursing woman

Contraindicated (0) Serious (3) betibeglogene autotemcel exagamglogene autotemcel lovotibeglogene autotemcel

Side effects of Deferoxamine Mesylate (Desferrioxamine Mesylate) : 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

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