(de fer OKS a meen)
Adjunct in the treatment of acute iron intoxication; treatment of chronic iron overload secondary to multiple transfusions
Canadian labeling (off-label use in the U.S.): Diagnosis of aluminum overload; treatment of chronic aluminum overload in patients with end-stage renal failure undergoing maintenance dialysis
Hypersensitivity to deferoxamine or any component of the formulation; patients with severe renal disease or anuria
Note: Canadian labeling does not include severe renal disease or anuria as contraindications.
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) (Perrone 2015). 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 or when severe toxicity is not evident is a subject of clinical debate (Howland 2015; Perrone 2015).
IM, IV: Initial: 1,000 mg, 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: 6,000 mg/day [per manufacturer])
Canadian labeling:
IM: Initial: 90 mg/kg/dose (maximum/dose: 2,000 mg) followed by 45 mg/kg every 4 to 12 hours as needed (maximum: 6000 mg/24 hours)
IV: 15 mg/kg/hour up to a maximum of 80 mg/kg/dose or maximum of 6,000 mg/24 hours
Chronic iron overload:
IM: 500 to 1,000 mg/day (maximum: 1000 mg/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: 1,000 to 2,000 mg/day or 20 to 40 mg/kg/day over 8 to 24 hours
Off-label dosing: IV, SubQ: 25 to 50 mg/kg over 8 to 10 hours 5 to 7 days per week (Brittenham, 2011)
Canadian labeling: IV, SubQ: 1,000 to 4,000 mg/day (20 to 60 mg/kg/day) over ~12 hours (may further increase iron excretion with infusion at the same dose over 24 hours). SubQ infusions are administered 4 to 7 days per week based on the degree of iron overload.
Diagnosis of aluminum-induced toxicity with CKD (off-label use; K/DOQI guidelines, 2003): IV: Test dose: 5 mg/kg during the last hour of dialysis if serum aluminum levels 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 is ≥50 mcg/L). Do not use if aluminum serum levels are >200 mcg/L.
Canadian labeling: Note: Measure serum aluminum levels prior to and after administration of deferoxamine. IV: Test dose: 5 mg/kg/dose (infusion rate not to exceed 15 mg/kg/hour) following hemodialysis (preferred) or during the last hour of dialysis if serum aluminum levels are >60 mcg/L in association with serum ferritin levels >100 mcg/L; continuous rise in serum aluminum over the next 24 to 48 hours suggests overload. Remeasure serum aluminum levels prior to next hemodialysis, test is considered positive if serum aluminum levels increase >150 mcg/L above baseline.
Treatment of aluminum toxicity with CKD (off-label use; K/DOQI guidelines, 2003): IV:
Administer after diagnostic deferoxamine test dose. Note: The risk for deferoxamine-associated neurotoxicity is increased if aluminum serum levels are >200 mcg/L; withhold deferoxamine and administer intensive dialysis until <200 mcg/L.
Aluminum rise ≥300 mcg/L: 5 mg/kg once a week 5 hours before dialysis for 4 months
Aluminum rise <300 mcg/L: 5 mg/kg once a week during the last hour of dialysis for 2 months
Canadian labeling: Treatment should be considered for symptomatic patients with serum aluminum levels >60 mcg/L and a positive deferoxamine test dose.
Hemodialysis: IV: 5 mg/kg/dose (infusion rate not to exceed 15 mg/kg/hour) once weekly for 3 months following hemodialysis (preferred) or during the last hour of dialysis administered. Withhold treatment for 1 month then perform deferoxamine test. Further treatment is not recommended if 2 consecutive tests (performed 1 month apart) yield an increase in serum aluminum levels <75 mcg/L.
Continuous ambulatory or cyclic peritoneal dialysis: Intraperitoneal (preferred), IM, SubQ infusion (slow), or IV infusion (slow): 5 mg/kg/dose once weekly prior to final daily exchange
Refer to adult dosing. May initiate at the lower end of the dosing range.
Acute iron toxicity: Children and Adolescents: 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) (Perrone 2015). 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 or when severe toxicity is not evident is a subject of clinical debate (Howland 2015; Perrone 2015).
IM: 90 mg/kg/dose every 8 hours (maximum: 6,000 mg/24 hours)
IV: 15 mg/kg/hour (maximum: 6,000 mg/24 hours)
Canadian labeling:
IM: Initial: 90 mg/kg/dose (maximum/dose: 1,000 mg) followed by 45 mg/kg every 4 to 12 hours as needed (maximum: 6,000 mg/24 hours)
IV: 15 mg/kg/hour up to a maximum of 80 mg/kg/dose or maximum of 6,000 mg/24 hours
Chronic iron overload: Children ≥3 years and Adolescents:
IV: 20 to 40 mg/kg/day over 8 to 12 hours for 5 to 7 days per week; dose should not exceed 40 mg/kg/day until growth has ceased
SubQ: 20 to 40 mg/kg/day over 8 to 12 hours (maximum: 1,000 to 2,000 mg/day)
Off-label dosing: IV, SubQ: 25 to 30 mg/kg over 8 to 10 hours 5 to 7 days per week (Brittenham, 2011)
Diagnosis of aluminum induced toxicity with CKD (off-label use; K/DOQI guidelines, 2003): Children and Adolescents: IV: Test dose: 5 mg/kg during the last hour of dialysis if serum aluminum levels 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 is ≥50 mcg/L). Do not use if aluminum serum levels are >200 mcg/L.
Treatment of aluminum toxicity with CKD (off-label use; K/DOQI guidelines, 2003): Children and Adolescents: IV: Administer after diagnostic deferoxamine test dose. Note: The risk for deferoxamine-associated neurotoxicity is increased if aluminum serum levels are >200 mcg/L; withhold deferoxamine and administer intensive dialysis until <200 mcg/L.
Aluminum rise ≥300 mcg/L: 5 mg/kg once a week 5 hours before dialysis for 4 months
Aluminum rise <300 mcg/L: 5 mg/kg once a week during the last hour of dialysis for 2 months
Severe renal disease or anuria: Use is contraindicated in the manufacturer 's U.S. labeling.
The following adjustments have been used by some clinicians (Aronoff, 2007): 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).
IM: Reconstitute with sterile water for injection (500 mg vial with 2 mL SWFI; 2000 mg vial with 8 mL SWFI) to a final concentration of 213 mg/mL
IV: Reconstitute with sterile water for injection (500 mg vial with 5 mL SWFI; 2000 mg vial with 20 mL SWFI) to a final concentration of 95 mg/mL; further dilute for infusion in sodium chloride 0.9%, sodium chloride 0.45%, D5W, or LR.
SubQ: Reconstitute with sterile water for injection (500 mg vial with 5 mL SWFI; 2000 mg vial with 20 mL SWFI) to a final concentration of 95 mg/mL
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 1,000 mg, infuse at 15 mg/kg/hour (although rates up to 40 to 50 mg/kg/hour have been given in patients with severe iron intoxication). 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 (Brittenham, 2011).
Diagnosis or treatment of aluminum-induced toxicity with CKD: Administer dose over 1 hour, during the last hour of dialysis (K/DOQI guidelines, 2003).
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 (Brittenham, 2011).
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 (Perrone 2015); may also be used in the treatment of chronic iron toxicity.
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.
Prior to reconstitution, store at ≤25 ‹ šC ( ≤77 ‚ °F). Following reconstitution, may be stored at room temperature for 24 hours, although the manufacturer recommends use begin within 3 hours of reconstitution. Do not refrigerate reconstituted solution. When stored at 30 ‹ šC in polypropylene infusion pump syringes, deferoxamine 250 mg/mL in sterile water for injection retained 95% of initial concentration for 14 days (Stiles, 1996).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Injection, as mesylate:
Desferal: 500 mg (1 ea); 2 g (1 ea [DSC])
Generic: 500 mg (1 ea); 2 g (1 ea)
Stable in D5W, LR, NS, sterile water for injection.
Ascorbic Acid: 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. Consider therapy modification
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. 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. 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. Consider therapy modification
Prochlorperazine: Deferoxamine may enhance the adverse/toxic effect of Prochlorperazine. Specifically, prolonged loss of consciousness has been reported. Consider therapy modification
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)
Dialysis patients: Serum aluminum (yearly; every 3 months in patients on aluminum-containing medications)
Aluminum-induced bone disease: Serum aluminum 2 days following test dose; test is considered positive if serum aluminum increases ≥50 mcg/L
TIBC may be falsely elevated with high serum iron concentrations or deferoxamine therapy. Imaging results may be distorted due to rapid urinary excretion of deferoxamine-bound gallium-67; discontinue deferoxamine 48 hours prior to scintigraphy.
Frequency not defined.
Cardiovascular: Flushing, hypotension, shock, tachycardia
Central nervous system: Brain disease (aluminum toxicity/dialysis-related), dizziness, headache, neuropathy (peripheral, sensory, motor, or mixed), paresthesia, seizure
Dermatologic: Skin rash, urticaria
Endocrine & metabolic: Growth suppression (children), hyperparathyroidism (aggravated), hypocalcemia
Gastrointestinal: Abdominal distress, abdominal pain, diarrhea, nausea, vomiting
Genitourinary: Dysuria, urine discoloration (reddish color)
Hematologic & oncologic: Dysplasia (metaphyseal; children <3 years; dose related), leukopenia, thrombocytopenia
Hepatic: Hepatic insufficiency, increased serum transaminases
Hypersensitivity: Anaphylaxis (with or without shock), angioedema, hypersensitivity
Infection: Infection (Yersinia, mucormycosis)
Local: Injection site reaction (burning, crust, edema, erythema, eschar, induration, infiltration, irritation, pain, pruritus, swelling, vesicles, wheal formation)
Neuromuscular & skeletal: Arthralgia, muscle spasm, myalgia
Ophthalmic: Blurred vision, cataract, chromatopsia, corneal opacity, decreased peripheral vision, decreased visual acuity, nocturnal amblyopia, optic neuritis, retinal pigment changes, scotoma, vision loss, visual field defect
Otic: Hearing loss, tinnitus
Renal: Acute renal failure, increased serum creatinine, renal tubular disease
Respiratory: Acute respiratory distress (dyspnea, cyanosis, and/or interstitial infiltrates), asthma
Miscellaneous: Fever
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.
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).
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.
C
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).
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.
IM, SubQ: Well absorbed
Distributed throughout body fluids
Plasma enzymes; binds with iron to form ferrioxamine (iron complex)
Primarily urine (as unchanged drug and ferrioxamine); feces (via bile)
14 hours; plasma: 20 to 30 minutes (Brittenham 2011)
<10%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience urine discoloration, headache, nausea, vomiting, diarrhea, muscle spasms, joint pain, muscle pain, or abdominal pain. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), tachycardia, severe dizziness, passing out, shortness of breath, burning or numbness feeling, bruising, bleeding, severe injection site irritation, vision changes, or hearing impairment (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.