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Pronunciation
(de fer OKS a meen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Adjunct in the treatment of acute iron intoxication; treatment of chronic iron overload secondary to multiple transfusions
Canadian labeling (unlabeled use in the U.S.): Diagnosis of aluminum overload; treatment of chronic aluminum overload in patients with end-stage renal failure undergoing maintenance dialysis
Use: Unlabeled
Diagnosis or treatment of aluminum induced toxicity associated with chronic kidney disease (CKD)
Pregnancy Risk Factor
C
Pregnancy Considerations
Skeletal anomalies and delayed ossification were observed in some but not all animal reproduction studies. Toxic amounts of iron or deferoxamine have not been noted to cross the placenta. In case of acute iron toxicity, treatment during pregnancy should not be withheld.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
It is not known if deferoxamine is excreted in human milk; the manufacturer recommends that caution be used if administered to a breast-feeding woman.
Contraindications
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.
Warnings/Precautions
Concerns related to adverse effects:
• Acute respiratory distress syndrome (ARDS): Deferoxamine has been associated with ARDS following excessively high-dose I.V. 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 I.V. infusion; administer I.M., by slow subcutaneous infusion, or slow I.V. 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, 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 excreted renally.
• Urine discoloration: Patients should be informed that urine may have a reddish color.
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 pre-existing cardiac failure.
Adverse Reactions
Frequency not defined.
Cardiovascular: Flushing, hypotension, shock, tachycardia
Central nervous system: Dizziness, encephalopathy (aluminum toxicity/dialysis-related), fever, headache, seizure
Dermatologic: Angioedema, rash, urticaria
Endocrine & metabolic: Growth retardation (children), hyperparathyroidism (aggravated), hypocalcemia
Gastrointestinal: Abdominal discomfort, abdominal pain, diarrhea, nausea, vomiting
Genitourinary: Dysuria, urine discoloration (reddish color)
Hematologic: Leukopenia, thrombocytopenia
Hepatic: Hepatic dysfunction, transaminases increased
Local: Injection site: Burning, crust, edema, erythema, eschar, induration, infiltration, irritation, pain, pruritus, swelling, vesicles, wheal formation
Neuromuscular & skeletal: Arthralgia, metaphyseal dysplasia (children <3 years; dose related), muscle spasms, myalgia, neuropathy (peripheral, sensory, motor, or mixed), paresthesia
Ocular: Blurred vision, cataract, corneal opacities, dyschromatopsia, loss of vision, night blindness, optic neuritis, peripheral vision impaired, retinal pigment abnormalities, scotoma, visual acuity decreased, visual field defects
Otic: Hearing loss, tinnitus
Renal: Acute renal failure, renal tubular disorders, serum creatinine increased
Respiratory: Acute respiratory distress syndrome (dyspnea, cyanosis, and/or interstitial infiltrates), asthma
Miscellaneous: Anaphylaxis (with or without shock), hypersensitivity reaction, infections (Yersinia, mucormycosis)
Metabolism/Transport Effects
None known.
Drug Interactions
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. Risk D: Consider therapy modification
Prochlorperazine: Deferoxamine may enhance the adverse/toxic effect of Prochlorperazine. Specifically, prolonged loss of consciousness has been reported. Risk D: Consider therapy modification
Storage
Prior to reconstitution, store at ≤25˚C (≤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˚C in polypropylene infusion pump syringes, deferoxamine 250 mg/mL in sterile water for injection retained 95% of initial concentration for 14 days (Stiles, 1996).
Reconstitution
I.M.: 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
I.V.: 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
Compatibility
Stable in D5W, LR, NS, sterile water for injection.
Mechanism of Action
Complexes with trivalent ions (ferric ions) to form ferrioxamine, which is removed by the kidneys, slows accumulation of hepatic iron and retards or eliminates progression of hepatic fibrosis. Also known to inhibit DNA synthesis in vitro.
Pharmacodynamics/Kinetics
Absorption: I.M., 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 half-life: 20-30 minutes)
Excretion: Primarily urine (as unchanged drug and ferrioxamine); feces (via bile)
Dosage
Acute iron toxicity: Note: The I.V. route 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, 2011). When severe symptoms are not present, the I.M. route may be used (per the manufacturer).
Children ≥3 years:
I.M.: 90 mg/kg/dose every 8 hours (maximum: 6000 mg/24 hours)
I.V.: 15 mg/kg/hour (maximum: 6000 mg/24 hours)
Canadian labeling:
I.M.: Initial: 90 mg/kg/dose (maximum/dose: 1000 mg) followed by 45 mg/kg every 4-12 hours as needed (maximum: 6000 mg/24 hours)
I.V.: 15 mg/kg/hour up to a maximum of 80 mg/kg/dose or maximum of 6000 mg/24 hours
Adults: I.M., I.V.: Initial: 1000 mg, may be followed by 500 mg every 4 hours for 2 doses; subsequent doses of 500 mg have been administered every 4-12 hours based on clinical response (maximum recommended dose: 6000 mg/day [per manufacturer])
Canadian labeling:
I.M.: Initial: 90 mg/kg/dose (maximum/dose: 2000 mg) followed by 45 mg/kg every 4-12 hours as needed (maximum: 6000 mg/24 hours)
I.V.: 15 mg/kg/hour up to a maximum of 80 mg/kg/dose or maximum of 6000 mg/24 hours
Chronic iron overload:
Children ≥3 years:
I.V.: 20-40 mg/kg/day over 8-12 hours for 5-7 days per week; dose should not exceed 40 mg/kg/day until growth has ceased
SubQ: 20-40 mg/kg/day over 8-12 hours (maximum: 1000-2000 mg/day)
Unlabeled dosing: I.V., SubQ: 25-30 mg/kg over 8-10 hours 5-7 days per week (Brittenham, 2011)
Adults:
I.M.: 500-1000 mg/day (maximum: 1000 mg/day)
I.V.: 40-50 mg/kg/day (maximum: 60 mg/kg/day) over 8-12 hours for 5-7 days per week
SubQ: 1000-2000 mg/day or 20-40 mg/kg/day over 8-24 hours
Unlabeled dosing: I.V., SubQ: 25-50 mg/kg over 8-10 hours 5-7 days per week (Brittenham, 2011)
Canadian labeling: I.V., SubQ: 1000-4000 mg/day (20-60 mg/kg/day) over ~12 hours (may further increase iron excretion with infusion at the same dose over 24 hours). SubQ infusions are administered 4-7 days per week based on the degree of iron overload.
Diagnosis of aluminum-induced toxicity with CKD (unlabeled use; K/DOQI guidelines, 2003): Children and Adults: I.V.: Test dose: 5 mg/kg during the last hour of dialysis if serum aluminum levels are 60-200 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.
Adults: I.V.: 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 24-48 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 (unlabeled use; K/DOQI guidelines, 2003): Children and Adults: I.V.:
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: Adults: Treatment should be considered for symptomatic patients with serum aluminum levels >60 mcg/L and a positive deferoxamine test dose.
Hemodialysis: I.V.: 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), I.M., SubQ infusion (slow), or I.V. infusion (slow): 5 mg/kg/dose once weekly prior to final daily exchange
Dosing adjustment in renal impairment: 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:
Clcr >50 mL/minute: No adjustment required
Clcr 10-50 mL/minute, CRRT: Administer 25% to 50% of normal dose
Clcr<10 mL/minute, hemodialysis, peritoneal dialysis: Avoid use
Dosage adjustment in hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Administration: I.M.
I.M. administration may be used for patients with acute iron toxicity that do not exhibit severe symptoms (per the manufacturer); may also be used in the treatment of chronic iron toxicity.
Administration: I.V.
Urticaria, flushing of the skin, hypotension, and shock have occurred following rapid I.V. administration; limiting infusion rate to 15mg/kg/hour may help avoid infusion-related adverse effects.
Acute iron toxicity: The manufacturer states that the I.M. route is preferred; however, the I.V. route is generally preferred in patients with severe toxicity (ie, patients in shock). For the first 1000 mg, infuse at 15 mg/kg/hour. Subsequent doses may be given over 4-12 hours at a rate not to exceed 125 mg/hour.
Chronic iron overload: Administer over 8-12 hours for 5-7 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 I.V. 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).
Administration: Other
SubQ: When administered for chronic iron overload, administration over 8-12 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).
Monitoring Parameters
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
Reference Range
Iron, serum: Normal: 50-160 mcg/dL; peak levels >500 mcg/dL 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)
Test Interactions
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.
Dietary Considerations
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.
Patient Education
You will be monitored closely for effects of this medication and frequent blood or urine tests may be necessary. Your urine may show a reddish discoloration. Report chest pain; rapid heartbeat; headache; pain, swelling, or irritation at infusion site; skin rash; changes or loss of hearing or vision; or acute abdominal or leg cramps.
Geriatric Considerations
Postmarketing reports suggest a possible increased risk of ocular disorders (color blindness, maculopathy, and scotoma) in patients ≥65 years of age; a relationship to dose is unclear. Geriatric patients may also be at increased risk of hearing loss or deafness.
Additional Information
Oncology Comment: The National Comprehensive Cancer Network (NCCN) guidelines for myelodysplastic syndromes (MDS) recommend considering iron chelation therapy in low- or intermediate-risk MDS patients to decrease iron overload due to multiple transfusions (v.1.2012). Treatment (subcutaneous deferoxamine or oral deferasirox) is generally recommended in MDS patients who have received >20-30 RBC transfusions. For those with serum ferritin levels >2500 mcg/L, the goal to decrease ferritin levels to <1000 mcg/L.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
Loss of consciousness has been reported with concurrent use of prochlorperazine
Nursing: Physical Assessment/Monitoring
Infuse slowly and monitor infusion site. Monitor for acute reactions; urticaria, hypotension, and shock can occur following rapid I.V. administration. With chronic therapy, perform ophthalmologic exam (fundoscopy, slit-lamp exam) and audiometry. Teach patient proper injection technique and syringe/needle disposal. Monitor for adverse cardiac, respiratory, or CNS symptoms and teach patient importance of reporting adverse symptoms.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as mesylate: 500 mg, 2 g
Desferal®: 500 mg, 2 g
Pricing: U.S. (www.drugstore.com)
Solution (reconstituted) (Desferal)
500 mg (4): $111.34
References
Allain P, Mauras Y, Chaleil D, et al, “Pharmacokinetics and Renal Elimination of Desferrioxamine and Ferrioxamine in Healthy Subjects and Patients With Haemochromatosis,” Br J Clin Pharmacol, 1987, 24(2):207-12.
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 116.
Bacon BR, Adams PC, Kowdley KV, et al, “Diagnosis and Management of Hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Disease,” Hepatology, 2011, 54(1):328-43.
Brittenham GM. “Iron-Chelating Therapy for Transfusional Iron Overload,” N Engl J Med, 2011, 364(2):146-56.
Chang TPY and Rangan C, “Iron Poisoning-A Literature-Based Review of Epidemiology, Diagnosis, and Management,” Pediatr Emerg Care, 2011, 27(!0):978-85.
“K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease, Guideline 6. Serum Calcium and Calcium-Phosphorus Product.” Available at http://www.kidney.org/professionals/KDOQI/guidelines_bone/Guide11.htm
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Myelodysplastic Syndromes,” Version 1.2012. Available at http://www.nccn.org/professionals/physician_gls/PDF/mds.pdf
Perrone J, “Iron,” Goldfrank's Toxicologic Emergencies, 9th ed, Nelson LS, Hoffman RS, Lewin NA, et al, eds, New York, NY: McGraw-Hill Companies, Inc, 2011.
Stiles ML, Allen LV, and Prince SJ, “Stability of Deferoxamine Mesylate, Floxuridine, Fluorouracil, Hydromorphone Hydrochloride, Lorazepam, and Midazolam Hydrochloride in Polypropylene Infusion-Pump Syringes,” Am J Health Syst Pharm, 1996, 53(13):1583-8.
Valentine K, Mastropietro C, and Sarnaik AP, “Infantile Iron Poisoning: Challenges in Diagnosis and Management,” Pediatr Crit Care Med, 2009, 10(3):e31-3.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
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