Version May 2024
Acute iron toxicity: Note: The IV route is preferred and is used when severe toxicity is evidenced by cardiovascular collapse or systemic symptoms (coma, shock, metabolic acidosis, or gastrointestinal bleeding) or potentially severe intoxications (peak serum iron level >500 mcg/dL) (Ref). The IM route may be used (per the manufacturer) but is not preferred and rarely indicated. The use of deferoxamine in situations in which the peak serum iron concentration is <500 mcg/dL and when severe toxicity is not evident is a subject of clinical debate (Ref).
IM, IV: Initial: 1 g, may be followed by 500 mg every 4 hours for 2 doses; subsequent doses of 500 mg have been administered every 4 to 12 hours based on clinical response (maximum recommended dose: 6 g/day [per manufacturer]).
Chronic iron overload:
IM: 500 mg to 1 g/day (maximum: 1 g/day).
IV: 40 to 50 mg/kg/day (maximum: 60 mg/kg/day) over 8 to 12 hours for 5 to 7 days per week.
SUBQ: 1 to 2 g/day or 20 to 40 mg/kg/day (maximum: 60 mg/kg/day) over 8 to 24 hours for 5 to 7 days per week.
Off-label dosing: IV, SUBQ: 25 to 50 mg/kg over 8 to 10 hours 5 to 7 days per week (Ref)
Diagnosis of aluminum-induced toxicity with CKD (off-label use) (Ref): IV: Test dose: 5 mg/kg during the last hour of dialysis if baseline serum aluminum concentrations are 60 to 200 mcg/L, or clinical signs/symptoms of toxicity, or aluminum exposure prior to parathyroid surgery. Measure aluminum just prior to deferoxamine; remeasure 2 days later (test is positive if serum aluminum increases by ≥50 mcg/L). Do not use if unstimulated aluminum serum concentrations are >200 mcg/L to avoid deferoxamine-induced neurotoxicity.
Treatment of aluminum toxicity with CKD (off-label use) (Ref): IV:
Administer after diagnostic deferoxamine test dose. Note: The risk for deferoxamine-associated neurotoxicity is increased if unstimulated aluminum serum concentrations are >200 mcg/L; do not perform the deferoxamine-stimulation test and administer intensive dialysis until <200 mcg/L.
If the serum aluminum concentration rises to ≥300 mcg/L two days after the deferoxamine test dose or there are side effects after the deferoxamine-stimulation test: 5 mg/kg once a week 5 hours before dialysis for 4 months. Then discontinue deferoxamine for one month and perform the deferoxamine-stimulation test again.
If the serum aluminum concentration is <300 mcg/L two days after the deferoxamine test dose and there are no side effects after the deferoxamine-stimulation test: 5 mg/kg once a week during the last hour of dialysis for 2 months. The discontinue deferoxamine for one month and perform the deferoxamine-stimulation test again.
Severe renal disease or anuria: Use is contraindicated in the manufacturer's US labeling.
The following adjustments have been used by some clinicians (Ref): Adults:
CrCl >50 mL/minute: No adjustment required
CrCl 10 to 50 mL/minute, CRRT: Administer 25% to 50% of normal dose
CrCl<10 mL/minute, hemodialysis, peritoneal dialysis: Avoid use
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Initiate at the lower end of the dosing range.
Refer to adult dosing. May initiate at the lower end of the dosing range.
(For additional information see "Deferoxamine: Pediatric drug information")
Acute iron intoxication: Limited data available:
Note: The IV route is preferred and is used when severe toxicity is evidenced by cardiovascular collapse or systemic symptoms (coma, shock, metabolic acidosis, or GI bleeding) or potentially severe intoxications (peak serum iron level >500 mcg/dL) (Ref). The IM route may be used (per the manufacturer) but is not preferred and rarely indicated. The use of deferoxamine in situations in which the peak serum iron concentration is <500 mcg/dL and when severe toxicity is not evident is a subject of clinical debate (Ref).
Continuous IV infusion: Infants, Children, and Adolescents: Continuous IV infusion: Initial: 15 mg/kg/hour and reduce rate as clinically indicated; maximum daily dose: 80 mg/kg/day and not to exceed 6 g/day (Ref).
IV: Infants, Children, and Adolescents: IV: Initial: 20 mg/kg (maximum dose: 1,000 mg/dose) administered no faster than 15 mg/kg/hour followed by 10 mg/kg (maximum dose: 500 mg/dose) over 4-hour intervals for 2 doses; subsequent doses of 10 mg/kg (maximum dose: 500 mg/dose) over 4 to 12 hours may be repeated depending upon the clinical response; maximum daily dose: 6 g/day; this dosing may also be used IM if symptoms not severe (Ref).
IM: Children and Adolescents: IM: 90 mg/kg/dose for one dose, then 45 mg/kg/dose every 4 to 12 hours as needed; maximum single dose: Children: 1,000 mg/dose; Adults: 2,000 mg/dose; maximum daily dose: 6 g/day (Ref); others have used 50 mg/kg/dose every 6 hours with maximum daily dose: 6 g/day (Ref); may also use intermittent IV dosing (see above).
Chronic iron overload:
General dosing:
IV:
Children ≥3 years and Growing Adolescents: IV: 20 to 40 mg/kg/day over 8 to 12 hours, 5 to 7 days per week, usual maximum daily dose: 40 mg/kg/day.
Adolescents once growth has ceased: 40 to 50 mg/kg/day over 8 to 12 hours, 5 to 7 days per week, usual maximum daily dose: 60 mg/kg/day.
SUBQ: Children ≥3 years and Adolescents: SUBQ infusion via a portable, controlled infusion device: 20 to 40 mg/kg/day over 8 to 12 hours 3 to 7 days per week; maximum daily dose: 2,000 mg/day. Doses >60 mg/kg/day have not been shown to provide additional benefit (Ref).
Sickle cell disease, chronic iron overload: Children and Adolescents: SUBQ infusion: 25 mg/kg/day over 8 hours; dose and duration may be increased as needed (Ref).
Thalassemia, chronic iron overload: Note: A lower dose may be required if the ferritin levels are low. In general, the therapeutic index should be kept <0.025 at all times. Therapeutic index = mean daily deferoxamine dose (mg/kg)/ferritin (mcg/L) (Ref):
Children and Growing Adolescents: SUBQ infusion: 20 to 40 mg/kg/day over 8 to 12 hours, 6 to 7 nights per week, maximum daily dose: 40 mg/kg/day.
Adolescents once growth has ceased:
SUBQ infusion (preferred): 40 to 60 mg/kg/day over 8 to 12 hours, 6 to 7 nights per week, maximum daily dose: 2,000 mg/day.
SUBQ bolus: 45 mg/kg/dose, 5 times per week.
Aluminum-induced bone disease in chronic renal failure: Limited data available:
Note: Intended for predialysis serum aluminum concentration of 60 to 200 mcg/L; do not start chelation therapy if serum aluminum concentration >200 mcg/L; intensive dialysis (6 days per week with a high flux dialysis membrane) should be used until serum aluminum concentration decreases below 200 mcg/L (Ref):
Children and Adolescents:
Test (diagnostic) dose: IV: 5 mg/kg as a single dose infused over the last hour of dialysis; measure serum aluminum concentration 2 days later; depending upon the change in serum aluminum concentration, treatment with deferoxamine may be indicated (see Treatment below).
Treatment: Monitor serum aluminum levels closely. See National Kidney Foundation guidelines for additional details on treatment algorithms.
Aluminum serum concentration rise to ≥300 mcg/L or adverse effects with test dose: IV: 5 mg/kg once a week 5 hours before dialysis for 4 months.
Aluminum serum concentration rise to <300 mcg/L: IV: 5 mg/kg once a week during the last hour of dialysis for 2 months.
Manufacturer's labeling: Severe renal disease or anuria: Use is contraindicated; in adults with impairment, dosage adjustment is suggested.
There are no dosage adjustments provided in the manufacturer's labeling (not studied).
The following adverse drug reactions are derived from product labeling unless otherwise specified. Frequency not defined.
Frequency not defined:
Cardiovascular: Hypotension, shock, tachycardia
Dermatologic: Skin rash, urticaria
Endocrine & metabolic: Growth retardation (children)
Gastrointestinal: Abdominal distress, abdominal pain, diarrhea, nausea, vomiting
Genitourinary: Dysuria
Hematologic & oncologic: Dysplasia (metaphyseal), leukopenia, thrombocytopenia
Hepatic: Hepatic impairment, increased serum transaminases
Hypersensitivity: Anaphylaxis (including anaphylactic shock), angioedema, hypersensitivity reaction
Infection: Infection (including Yersinia infections and mucormycosis)
Local: Injection-site reaction (including burning sensation at injection site, crusted skin, erythema at injection site, induration at injection site, injection-site pruritus, irritation at injection site, localized vesiculation, pain at injection site, swelling at injection site, urticaria at injection site)
Nervous system: Dizziness, headache, neuropathy (peripheral motor neuropathy, peripheral neuropathy, peripheral sensory neuropathy, and polyneuropathy), paresthesia, seizure
Neuromuscular & skeletal: Arthralgia, muscle spasm, myalgia
Ophthalmic: Blurred vision, cataract, corneal opacity, decreased peripheral vision, decreased visual acuity, night blindness, optic neuritis, retinal pigment changes, scotoma, vision color changes (including chromatopsia), vision loss, visual field defect
Otic: Hearing loss (including high frequency hearing loss and sensorineural hearing loss), tinnitus
Renal: Acute kidney injury, increased serum creatinine, renal failure syndrome, renal tubular disease
Respiratory: Acute respiratory distress syndrome, asthma
Miscellaneous: Fever
Hypersensitivity to deferoxamine or any component of the formulation; patients with severe renal disease or anuria
Concerns related to adverse effects:
• Acute respiratory distress syndrome (ARDS): Deferoxamine has been associated with ARDS following excessively high-dose IV treatment of acute iron intoxication or thalassemia; has been reported in children and adults.
• Auditory effects: Auditory disturbances (tinnitus and high frequency hearing loss) have been reported following prolonged administration, at high doses, or in patients with low ferritin levels; effects are generally reversible with early detection and immediate discontinuation. Elderly patients are at increased risk for hearing loss. Audiology exams are recommended with long-term treatment.
• Growth retardation: High deferoxamine doses and concurrent low ferritin levels are also associated with growth retardation. Growth velocity may partially resume to pretreatment rates after deferoxamine dose reduction.
• Infection: Patients with iron overload are at increased susceptibility to infection with Yersinia enterocolitica and Yersinia pseudotuberculosis; treatment with deferoxamine may enhance this risk; if infection develops, discontinue therapy until resolved.
• Infusion reactions: Flushing of the skin, hypotension, urticaria, and shock are associated with rapid IV infusion; administer by slow IV infusion, IM, or slow subcutaneous infusion only.
• Mucormycosis: Rare and serious cases of mucormycosis (including fatalities) have been reported with use; withhold treatment with signs and symptoms of mucormycosis.
• Ocular effects: Ocular disturbances (blurred vision; cataracts; corneal opacities; decreased visual acuity; impaired peripheral, color, and night vision; optic neuritis; retinal pigment abnormalities; retinopathy; scotoma; visual loss/defect) have been reported following prolonged administration, at high doses, or in patients with low ferritin levels; effects are generally reversible with early detection and immediate discontinuation. Elderly patients are at increased risk for ocular disorders. Periodic ophthalmic exams are recommended with long-term treatment.
• Renal effects: Increases in serum creatinine, acute renal failure and renal tubular disorders have been reported; monitor for changes in renal function. Deferoxamine is readily dialyzable. When iron is chelated with deferoxamine, the chelate is water-soluble and is excreted renally.
• Urine discoloration: Patients should be informed that urine may have a pink, reddish, or orange discoloration (often referred to as vin rosé discoloration).
Disease-related concerns:
• Aluminum toxicity: Treatment with deferoxamine in patients with aluminum toxicity may cause hypocalcemia and aggravate hyperparathyroidism. Deferoxamine may cause neurological symptoms (including seizure) in patients with aluminum-related encephalopathy receiving dialysis and may precipitate dialysis dementia onset.
• Hemochromatosis: Deferoxamine is not indicated for the treatment of primary hemochromatosis (treatment of choice is phlebotomy).
• Myasthenia gravis: Use may worsen or precipitate new myasthenia gravis (AAN [Narayanaswami 2021]; Krishnan 1995).
Concurrent drug therapy issues:
• Ascorbic acid: Combination treatment with ascorbic acid (>500 mg/day in adults) and deferoxamine may impair cardiac function (rare), effects are reversible upon discontinuation of ascorbic acid. If combination treatment is warranted, initiate ascorbic acid only after one month of regular deferoxamine treatment, do not exceed ascorbic acid dose of 200 mg/day for adults (in divided doses), 100 mg/day for children ≥10 years of age, or 50 mg/day in children <10 years of age; monitor cardiac function. Do not administer deferoxamine in combination with ascorbic acid in patients with preexisting cardiac failure.
Growth retardation in pediatric patients especially in patients ≤3 years has been associated with high doses (>60 mg/kg) and concurrent low ferritin levels; a reduction in deferoxamine dosage may partially improve growth velocity; monitor growth in children receiving chronic therapy closely.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection, as mesylate [preservative free]:
Desferal: 500 mg (1 ea)
Generic: 500 mg (1 ea); 2 g (1 ea)
Yes
Solution (reconstituted) (Deferoxamine Mesylate Injection)
2 g (per each): $37.20 - $62.16
500 mg (per each): $15.54
Solution (reconstituted) (Desferal Injection)
500 mg (per each): $41.67
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection, as mesylate:
Desferal: 500 mg (1 ea)
Generic: 500 mg (1 ea); 2 g (1 ea)
IV: Urticaria, flushing of the skin, hypotension, and shock have occurred following rapid IV administration; limiting infusion rate to 15 mg/kg/hour may help avoid infusion-related adverse effects.
Acute iron toxicity: The IV route is generally preferred in patients with severe toxicity (ie, patients in shock). For the first 1 g, infuse at 15 mg/kg/hour (although rates up to 40 mg/kg/hour have been recommended in patients with severe iron intoxication (Ref)). Subsequent doses may be given over 4 to 12 hours at a rate not to exceed 125 mg/hour.
Chronic iron overload: Administer over 8 to 12 hours for 5 to 7 days per week; rate not to exceed 15 mg/kg/hour. In patients with poor compliance, deferoxamine may be administered on the same day of blood transfusion, either prior to or following transfusion; do not administer concurrently with transfusion. Longer infusion times (24 hours) and IV administration may be required in patients with severe cardiac iron deposition (Ref).
Diagnosis or treatment of aluminum-induced toxicity with CKD: Administer dose over 1 hour, during the last hour of dialysis (Ref).
SUBQ: When administered for chronic iron overload, administration over 8 to 12 hours for 5 to 7 days per week using a portable infusion pump is generally recommended; however, longer infusion times (24 hours) may also be used. Topical anesthetic or glucocorticoid creams may be used for induration or erythema (Ref).
IM: IM administration may be used for patients with acute iron toxicity that do not exhibit severe symptoms (per the manufacturer), but the IV route is preferred (Ref); may also be used in the treatment of chronic iron toxicity.
Parenteral:
IM: Preferred route of administration for acute iron ingestion in patients not in shock per the manufacturer's labeling.
IV: Administer as intermittent IV infusion or as continuous IV infusion; maximum rate: 15 mg/kg/hour; may consider reducing infusion rate to <125 mg/hour after the first 1,000 mg have been infused.
SUBQ: When administered for chronic iron overload, administration over 8 to 12 hours using a portable infusion pump is generally recommended; however, longer infusion times (24 hours) may also be used. Topical anesthetic or glucocorticoid creams may be used for induration or erythema (Ref).
Acute iron toxicity: Adjunct in the treatment of acute iron intoxication
Chronic iron overload: Treatment of chronic iron overload secondary to multiple transfusions (often due to the presence of thalassemia major or sickle cell disease [Borgna-Pignatti 2015; Marsella 2015])
Diagnosis or treatment of aluminum-induced toxicity associated with chronic kidney disease (CKD)
Deferoxamine may be confused with cefuroxime, deferasirox, deferiprone
Desferal may be confused with desflurane, Desyrel, Dexferrum
Desferal [US, Canada, and multiple international markets] may be confused with Deseril brand name for methysergide [Australia, Belgium, Great Britain, Netherlands]; Disophrol brand name for dexbrompheniramine and pseudoephedrine [Czech Republic, Poland, Turkey]
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Ascorbic Acid: May enhance the adverse/toxic effect of Deferoxamine. Left ventricular dysfunction is of particular concern. Management: Limit the ascorbic acid dose to 200 mg/day (given in divided doses) in adult patients. In general, limit ascorbic acid to 50 mg daily for pediatric patients under 10 years old and 100 mg daily for older pediatric patients. Risk D: Consider therapy modification
Betibeglogene Autotemcel: Iron Chelators may diminish the therapeutic effect of Betibeglogene Autotemcel. Management: Avoid use of iron chelators for at least 7 days prior to conditioning therapy preceding betibeglogene autotemcel treatment, and avoid use of myelosuppressive iron chelators for at least 6 months after betibeglogene autotemcel. Risk X: Avoid combination
Exagamglogene Autotemcel: Iron Chelators may enhance the myelosuppressive effect of Exagamglogene Autotemcel. Iron Chelators may diminish the therapeutic effect of Exagamglogene Autotemcel. Risk X: Avoid combination
Gallium Citrate Ga-67: Deferoxamine may diminish the diagnostic effect of Gallium Citrate Ga-67. Management: Discontinue deferoxamine 48 hours prior to scintigraphy with gallium citrate Ga-67. Risk D: Consider therapy modification
Lovotibeglogene Autotemcel: Iron Chelators may enhance the myelosuppressive effect of Lovotibeglogene Autotemcel. Iron Chelators may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Deferoxamine. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function. Risk D: Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Deferoxamine. Left ventricular dysfunction is of particular concern. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function. Risk D: Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May enhance the adverse/toxic effect of Deferoxamine. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function. Risk D: Consider therapy modification
Prochlorperazine: Deferoxamine may enhance the adverse/toxic effect of Prochlorperazine. Specifically, prolonged loss of consciousness has been reported. Management: Consider alternatives to prochlorperazine in patients receiving deferoxamine, due to a risk of temporary impairment of consciousness (potentially lasting for days) with the combination. Risk D: Consider therapy modification
Adverse events have been observed in animal reproduction studies. Toxic amounts of iron or deferoxamine have not been noted to cross the placenta; however, the metabolic effects of a maternal overdose may adversely affect the fetus. In case of acute iron toxicity, treatment during pregnancy should not be withheld (Chang 2011).
It is not known if deferoxamine is present in breast milk.
One patient who received deferoxamine during lactation for beta thalassemia exhibited normal breast milk iron concentrations. Adverse events were not reported in her breastfed twins (Surbek 1998). The manufacturer recommends that caution be exercised when administering to breastfeeding women.
Vitamin C supplements may need to be limited. The manufacturer recommends a maximum ascorbic acid dose of 200 mg/day in adults (given in divided doses), 100 mg/day in children ≥10 years of age, or 50 mg/day in children <10 years of age. Avoid concurrent use with ascorbic acid in patients with heart failure.
Serum iron, ferritin, total iron-binding capacity, CBC with differential, renal function tests (serum creatinine), liver function tests, serum chemistries; ophthalmologic exam (visual acuity tests, fundoscopy, slit-lamp exam) and audiometry with long-term treatment; growth and body weight in children (every 3 months). When deferoxamine complexes with iron it forms a water-soluble compound (ferrixoamine) that imparts discoloration of the urine; often described as vin rosé (dark pink) discoloration to the urine (Fernández 2014). However, other than being aware of that it may occur, its presence or absence should not be used as a therapeutic endpoint.
Dialysis patients: Serum aluminum (yearly; every 3 months in patients on aluminum-containing medications)
Aluminum-induced bone disease: Serum aluminum concentration 2 days following deferoxamine test dose; test is considered positive if the serum aluminum increases ≥50 mcg/L
Iron, serum: Normal: 50 to 160 mcg/dL; peak levels >500 mcg/dL may be associated with toxicity. Consider treatment in symptomatic patients with levels ≥350 mcg/dL; toxicity cannot be excluded with serum iron levels <350 mcg/dL
Aluminum, serum: <20 mcg/L recommended baseline level in dialysis patients (K/DOQI 2003)
Complexes with trivalent ions (ferric ions), primarily in the vascular space, to form ferrioxamine, which is eliminated in the urine by the kidneys. One hundred milligrams of deferoxamine will bind about 8.5 mg of free circulating elemental iron (85 mg per 1,000 mg dose) but does not remove iron from transferrin or hemoglobin. Binding of cytoplasmic free iron reduces the free iron-induced disruption of mitochondrial cell membranes and enzyme systems. Ferrioxamine may create a pink- to red- or orange-colored urine as it is being excreted; however, the presence or absence of urine discoloration should not be used as a therapeutic endpoint.
Absorption: IM, SUBQ: Well absorbed
Distribution: Distributed throughout body fluids
Protein binding: <10%
Metabolism: Plasma enzymes; binds with iron to form ferrioxamine (iron complex)
Half-life elimination: 14 hours; plasma: 20 to 30 minutes (Brittenham 2011)
Excretion: Primarily urine (as unchanged drug and ferrioxamine); feces (via bile)
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