Deferoxamine is an iron-chelating agent used in the treatment of acute iron intoxication and chronic iron overload secondary to multiple blood transfusions (i.e., transfusional iron overload) in patients with chronic anemia. Initially produced as a ferric compound, the drug has the iron component chemically removed, resulting in an iron-free ligand. This ligand is then used to bind excess ferric ions in cases of iron poisoning or iron overload associated with transfusion-dependent anemia. Deferoxamine is not indicated for the treatment of primary hemochromatosis, since phlebotomy is the method of choice for removing excess iron in this disorder. Deferoxamine also chelates aluminum and increases its renal clearance, and the drug can be used to diagnose and treat aluminum overload in patients with chronic kidney disease on dialysis.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Administer intravenously or subcutaneously. Although the manufacturer indicates that intramuscular injection is the preferred route unless the patient is in shock, available literature supports using continuous intravenous infusion for any patient with acute iron toxicity. Furthermore, it appears that subcutaneous infusion over 8 to 12 hours is the preferred route of administration in most patients with chronic iron overload.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if visibly opaque particles, discoloration or foreign particles are observed. The reconstituted deferoxamine solution is an isotonic, clear and colorless to slightly-yellowish solution.
-Deferoxamine reconstituted with Sterile Water for Injection is for single use only. Discard any unused portion.
Intravenous Administration
Reconstitution
-Reconstitute each 500-mg vial with 5 mL of Sterile Water for Injection for a resultant concentration of 95 mg/mL.
-Storage: If not used immediately, store at room temperature between 20 and 25 degrees C (68 to 77 degrees F) for a maximum period of 24 hours. Do not refrigerate reconstituted solution.
Dilution
-Dilute the reconstituted IV solution in 150 mL of 5% Dextrose for injection, 0.45% Sodium Chloride for injection, 0.9% Sodium Chloride for injection, or Lactated Ringer's Injection for a final concentration of 3 to 3.5 mg/mL.
-Storage: If not used immediately, store at room temperature between 20 and 25 degrees C (68 to 77 degrees F) for a maximum period of 24 hours.
Continuous Intravenous Infusion
-Infuse IV generally at a maximum rate of 15 mg/kg/hour; however, higher infusion rates up to 35 mg/kg/hour have been safely used. Rapid infusion may cause hypotension, erythema, urticaria, wheezing, convulsions, tachycardia, or shock.
-If the patient is also receiving blood, deferoxamine should be administered in a line that is separate from the blood.
Intramuscular Administration
Reconstitution
-Reconstitute each 500-mg vial with 2 mL of Sterile Water for Injection for a resultant concentration of 213 mg/mL.
-Storage: If not used immediately, store at room temperature between 20 and 25 degrees C (68 to 77 degrees F) for a maximum period of 24 hours. Do not refrigerate reconstituted solution.
Intramuscular Injection
-Inject deeply into a large muscle mass.
Subcutaneous Administration
Reconstitution
-Reconstitute each 500-mg vial with 5 mL of Sterile Water for Injection for a resultant concentration of 95 mg/mL.
-Storage: If not used immediately, store at room temperature between 20 and 25 degrees C (68 to 77 degrees F) for a maximum period of 24 hours. Do not refrigerate reconstituted solution.
Continuous Subcutaneous Infusion
-Infuse over 8 to 12 hours using a portable, light-weight infusion pump; longer infusion times up to 24 hours may be used.
-Deferoxamine is not formulated to support subcutaneous bolus injection.
Ocular toxicity has been reported with deferoxamine therapy. The ocular disturbances observed have included blurred vision; cataracts after prolonged administration in chronic iron overload; impaired color vision, night blindness, optic neuritis, corneal opacification, retinal deposits, retinopathy, and visual impairment (decreased acuity, loss of vision, scotomata, or other visual field defects). In most cases, ocular disturbances were reversible upon immediate cessation of treatment. Risk factors for ocular disturbances include prolonged treatment duration, higher doses, or low ferritin levels. The risk of ocular toxicity may be increased in elderly patients. Visual acuity tests, slit-lamp examinations, and funduscopy are recommended periodically in patients who will be treated for long periods of time. Toxicity is more likely to be reversed if symptoms or test abnormalities are detected early.
Ototoxicity has been reported with deferoxamine therapy. This is usually manifest as auditory toxicity. The auditory toxicities reported have included tinnitus and hearing loss, including high frequency sensorineural hearing loss. Risk factors for auditory disturbances include prolonged treatment duration, higher doses, or low ferritin levels. The risk of hearing loss and deafness may be increased in elderly patients. In most cases, auditory disturbances were reversible upon immediate cessation of treatment. Audiometry is recommended periodically in patients who will be treated for long periods of time. Toxicity is more likely to be reversed if symptoms or test abnormalities are detected early.
Deferoxamine may increase the risk of Yersinia enterocolitica and Yersinia pseudotuberculosis infection. Avoid starting deferoxamine treatment in patients with active Yersinia infections. If an infection develops, interrupt deferoxamine treatment until the infection is resolved. Cases of mucormycosis, some with a fatal outcome, have occurred in deferoxamine-treated patients. Signs or symptoms are specific to the site of infection. If mucormycosis is suspected, discontinue deferoxamine, conduct mycological testing, and treat immediately.
Neurological disturbances reported during deferoxamine therapy include dizziness, headache, fever, peripheral neuropathy, and paresthesias. In dialysis patients with aluminum-related encephalopathy, deferoxamine may exacerbate seizures or other neurological dysfunction, most likely due to an acute increase in aluminum concentrations. Deferoxamine may also precipitate the onset of dialysis encephalopathy or dementia. Further, use of deferoxamine in patients with aluminum overload may result in hypocalcemia and aggravation of hyperparathyroidism.
Hypersensitivity reactions, including anaphylactic shock, angioedema, hypotension, rash, urticaria, and skin flushing have occurred in deferoxamine-treated patients. These reactions typically occur when deferoxamine was administered by rapid intravenous injection. Therefore, administer deferoxamine by slow intravenous or subcutaneous infusion. Although the manufacturer recommends intramuscular administration of deferoxamine, this route is not preferred and is typically not used in clinical practice. Localized irritation, pain, burning, swelling, induration, infiltration, pruritus, erythema, wheal formation, eschar, crust, vesicles, and local edema may also occur as an injection site reaction.
Gastrointestinal adverse events associated with deferoxamine therapy include diarrhea, abdominal pain, nausea, and vomiting.
Cases of thrombocytopenia and leukopenia have been reported with deferoxamine use.
High doses of deferoxamine and concomitant low ferritin levels have been associated with growth inhibition and bone changes (e.g., metaphyseal dysplasia) in pediatric patients. The maximum recommended daily dose in pediatric patients with chronic iron overload is 40 mg/kg/day until growth (body weight and linear growth) has ceased. Others recommend that the dose of deferoxamine in young children should not exceed 25 to 35 mg/kg/day to minimize interference with growth and skeletal development. After reduction of deferoxamine dose, growth velocity may partially resume to pre-treatment rates. Monitor growth (weight and height) in pediatric patients treated with deferoxamine every 3 months. Other musculoskeletal adverse events associated with deferoxamine include arthralgia, myalgia, and muscle cramps or spasms.
Acute respiratory distress syndrome (ARDS), with symptoms of dyspnea, cyanosis, and/or interstitial infiltrates, following treatment with excessively high intravenous doses of deferoxamine, has been reported in patients with acute iron intoxication or thalassemia. Do not exceed the recommended daily doses. Asthma may also occur in association with a local injection site reaction.
Hepatic dysfunction and elevated hepatic enzymes (increased transaminases) have been reported with deferoxamine use.
Acute renal failure (unspecified), increased serum creatinine, renal tubular disorders, and dysuria have been reported with deferoxamine use.
Cardiovascular adverse events observed in recipients of deferoxamine include sinus tachycardia, hypotension, and cardiogenic shock. Cardiac dysfunction has occurred in deferoxamine-treated patients with severe chronic iron overload following concomitant treatment with high doses of vitamin C (more than 500 mg daily in adults). The cardiac dysfunction was reversible when vitamin C was discontinued. Do not use ascorbic acid concurrently with deferoxamine in patients with known cardiac decompensation or heart failure. To decrease the risk of cardiac dysfunction, the following are recommended: initiate vitamin C supplementation only after the initial month of deferoxamine therapy; only administer vitamin C to patients receiving deferoxamine regularly; avoid vitamin C doses more than 200 mg/day in adults, 100 mg/day in older pediatric patients, and 50 mg/day in pediatric patients younger than 10 years; and monitor cardiac function during concomitant therapy.
Hypersensitivity reactions, including anaphylactic shock, angioedema, hypotension, rash, urticaria, and skin flushing have occurred in deferoxamine-treated patients. These reactions typically occur when deferoxamine was administered by rapid intravenous injection. Therefore, administer deferoxamine by slow intravenous or subcutaneous infusion. Although the manufacturer recommends intramuscular administration of deferoxamine, this route is not preferred and is typically not used in clinical practice.
Deferoxamine is not indicated for the treatment of primary hemochromatosis, since phlebotomy is the method of choice for removing excess iron in this disorder.
Deferoxamine is contraindicated for use in patients with anuria or severe renal disease (especially renal failure) because the drug and the iron chelate are eliminated primarily by the kidneys. Increases in serum creatinine, acute renal failure, and renal tubular disorders have been reported with deferoxamine use. Monitor serum creatinine to assess for changes in renal function. In dialysis patients with aluminum-related encephalopathy, high doses of deferoxamine may exacerbate neurological dysfunction (e.g., seizures), possibly due to an acute increase in circulating aluminum. Deferoxamine may precipitate the onset of dialysis dementia. Treatment with deferoxamine in the presence of aluminum overload may result in decreased serum calcium and aggravation of hyperparathyroidism.
Deferoxamine increases the urinary excretion of iron, in the form of an iron chelate. The urinary excretion of parenterally administered iron has been reported to exacerbate latent pyelonephritis. It is possible that deferoxamine therapy might also exacerbate pyelonephritis; caution is recommended.
Deferoxamine may increase the risk of Yersinia enterocolitica and Yersinia pseudotuberculosis infection. Avoid starting deferoxamine treatment in patients with active Yersinia infections. If an infection develops, interrupt deferoxamine treatment until the infection is resolved. Cases of mucormycosis, some with a fatal outcome, have occurred in deferoxamine-treated patients. Signs or symptoms are specific to the site of infection. If mucormycosis is suspected, discontinue deferoxamine, conduct mycological testing, and treat immediately.
Deferoxamine may cause both ocular toxicity (i.e., vision loss, visual disturbance, cataracts) and ototoxicity (i.e., tinnitus, hearing impairment or loss). Risk factors for both ocular and auditory disturbances include prolonged treatment duration, higher doses, or low ferritin levels. In most cases, both ocular and auditory disturbances were reversible upon immediate cessation of treatment. Visual acuity tests, slit-lamp examinations, funduscopy, and audiometry are recommended periodically in patients treated for prolonged periods of time. Toxicity is more likely to be reversed if symptoms or test abnormalities are detected early. Furthermore, postmarketing reports indicate that color blindness, maculopathy, and scotoma adverse ocular effects may occur more commonly in geriatric patients, although whether these effects are dose-related in this population is not known. In addition, deafness and hearing loss may also be increased in elderly patients. In general, dose selection for elderly patients should be cautious, starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or drug therapy.
Deferoxamine may cause dizziness, which may impair the ability to drive a car or operate machinery. Patients should refrain from driving or operating machinery until they know how deferoxamine will affect their ability to engage in these activities.
Cardiac dysfunction has occurred in deferoxamine-treated patients with severe chronic iron overload following concomitant treatment with high doses of vitamin C (more than 500 mg daily in adults). The cardiac dysfunction was reversible when vitamin C was discontinued. Do not use ascorbic acid concurrently with deferoxamine in patients with known cardiac decompensation or heart failure. To decrease the risk of cardiac dysfunction, the following are recommended: initiate vitamin C supplementation only after the initial month of deferoxamine therapy; only administer vitamin C to patients receiving deferoxamine regularly; avoid vitamin C doses more than 200 mg/day in adults, 100 mg/day in older pediatric patients, and 50 mg/day in pediatric patients younger than 10 years; and monitor cardiac function during concomitant therapy.
High doses of deferoxamine and concomitant low ferritin levels have been associated with growth inhibition and bone changes (e.g., metaphyseal dysplasia) in pediatric patients. The maximum recommended daily dose in pediatric patients with chronic iron overload is 40 mg/kg/day until growth (body weight and linear growth) has ceased. Others recommend that the dose of deferoxamine in young children should not exceed 25 to 35 mg/kg/day to minimize interference with growth and skeletal development. After reduction of deferoxamine dose, growth velocity may partially resume to pre-treatment rates. Monitor growth (weight and height) in pediatric patients treated with deferoxamine every 3 months. Iron mobilization with deferoxamine is relatively poor in infants and children less than 3 years with relatively little iron overload. The drug should ordinarily not be given to such patients unless significant iron mobilization (e.g., 1 mg or more of iron per day) can be demonstrated.
Imaging results may be distorted because of the rapid urinary excretion of deferoxamine-bound gallium-67. Discontinue deferoxamine 48 hours prior to scintigraphy (including radiographic contrast administration with gallium-67).
There are no available data on deferoxamine use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. However, based on animal data, deferoxamine can cause malformations at doses less than the human dose. In animal reproduction studies, subcutaneous administration of deferoxamine to pregnant animals (mice or rabbits) during organogenesis at doses approximately 0.2 or greater (mice) and 0.7 or greater (rabbits) times the maximum recommended human dose resulted in maternal toxicity and adverse developmental outcomes. Advise pregnant women of the potential risk to a fetus. Consider the benefits and risks of deferoxamine for the mother and possible risks to the fetus when prescribing deferoxamine during pregnancy.
There are no data on the presence of deferoxamine or its metabolite in either human or animal milk, the effects on the breastfed child, or the effects on milk production. It is not known whether deferoxamine is excreted in human milk. Because of the potential for serious adverse reactions in the breastfed child, advise patients to avoid breast-feeding during treatment with deferoxamine, and for one week after the last dose.
Deferoxamine has not been studied in patients with hepatic disease. For patients with hepatic impairment, dose selection should usually start at the low end of the dosing range.
Counsel patients about the reproductive risk and contraception requirements during deferoxamine treatment. Deferoxamine can cause fetal harm when administered to pregnant women. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for 1 month after the last deferoxamine dose.
For the treatment of iron toxicity, including acute iron toxicity and chronic iron toxicity due to transfusional iron overload:
-for the treatment of acute iron toxicity as an adjunct:
NOTE: Initiation of deferoxamine is indicated for persons with serum iron concentration more than 500 mcg/dL, symptomatic persons with significant clinical manifestations of iron poisoning (i.e., lethargy, coma, hypovolemia, metabolic acidosis, coagulopathy), or persons with abdominal radiograph demonstrating significant number of pills despite attempts at gastrointestinal decontamination. Persons with peak iron concentrations of 350 to 500 mcg/dL should be evaluated for chelation therapy on an individual basis; the presence of significant clinical symptoms mandates treatment.
NOTE: In general, no more than 24 hours of deferoxamine administration is required. However, the most reliable indication for deferoxamine discontinuation is resolution of the signs and symptoms of iron toxicity. In addition, serum iron concentrations should no longer be elevated, usually less than 100 mcg/dL. However, it may be difficult to assess accurate iron concentrations in the presence of deferoxamine as they may be falsely low. In those persons that develop a vin-rose colored urine after the initiation of deferoxamine treatment, the urine should return to a normal color before the drug is discontinued. However, not all exhibit a change in urine color, or the urine may be dark and concentrated before deferoxamine initiation secondary to dehydration. If the urine does not change color with deferoxamine treatment, absence of color should not be used to determine length of therapy.
Intravenous dosage:
Adults: 15 mg/kg/hour continuous IV infusion until signs and symptoms of iron poisoning are resolved and serum iron concentration within normal range. Higher doses (up to 35 mg/kg/hour) have been safely used and may be needed in severe ingestions. Although the FDA-approved labeling recommends a maximum dosage of 6 g/24 hours, higher doses are often used (16 to 20 g/day) and may be clinically necessary. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.
Children and Adolescents 3 to 17 years: 15 mg/kg/hour continuous IV infusion until signs and symptoms of iron poisoning are resolved and serum iron concentration within normal range. Higher doses (up to 35 mg/kg/hour) have been safely used and may be needed in severe ingestions. Although the FDA-approved labeling recommends a maximum dosage of 6 g/24 hours, higher doses are often used (16 to 20 g/day) and may be clinically necessary. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.
Infants* and Children 1 to 2 years*: 15 mg/kg/hour continuous IV infusion until signs and symptoms of iron poisoning are resolved and serum iron concentration within normal range. Higher doses (up to 35 mg/kg/hour) have been safely used and may be needed in severe ingestions. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.
Intramuscular dosage:
NOTE: Although intramuscular administration is FDA-approved, this route is not preferred and is typically not used in clinical practice.
Adults: 1 g IM once, followed by 500 mg IM every 4 to 12 hours as needed based on clinical response. Although the FDA-approved labeling recommends a maximum dosage of 6 g/24 hours, higher doses are often used (16 to 20 g/day) and may be clinically necessary. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.
Children and Adolescents 3 to 17 years: 40 to 90 mg/kg/dose (Max: 2 g/dose) IM every 4 to 8 hours as needed based on clinical response. The FDA-approved dosage is 1 g IM once, followed by 500 mg IM every 4 to 12 hours as needed based on clinical response. Although the FDA-approved labeling recommends a maximum dosage of 6 g/24 hours, higher doses are often used (16 to 20 g/day) and may be clinically necessary. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.
Infants* and Children 1 to 2 years*: 40 to 90 mg/kg/dose IM every 4 to 8 hours as needed based on clinical response. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.
-for the treatment of chronic iron overload due to transfusional iron overload in persons with chronic anemia:
NOTE: Deferoxamine is not indicated for the treatment of chronic iron overload in persons with primary hemochromatosis; phlebotomy is the treatment of choice for this condition.
NOTE: In general, subcutaneous administration is the preferred route for chronic iron overload.
Subcutaneous infusion dosage:
Adults: 20 to 60 mg/kg/day subcutaneously over 8 to 24 hours for 5 to 7 days/week. General deferoxamine requirements by serum ferritin concentration are 25 mg/kg/day for serum ferritin below 2,000 ng/mL, 35 mg/kg/day for serum ferritin 2,000 to 3,000 ng/mL, and up to 55 mg/kg/day for serum ferritin more than 3,000 ng/mL. Do not regularly exceed an average daily dose of 50 mg/kg/day except when very intensive chelation is needed in persons who have completed growth. If ferritin concentrations decrease below 1,000 ng/mL, the risk of deferoxamine toxicity increases; consider lowering the total weekly dose in these cases.
Children and Adolescents 3 to 17 years: 20 to 60 mg/kg/day subcutaneously over 8 to 24 hours for 5 to 7 days/week. General deferoxamine requirements by serum ferritin concentration are 25 mg/kg/day for serum ferritin below 2,000 ng/mL, 35 mg/kg/day for serum ferritin 2,000 to 3,000 ng/mL, and up to 55 mg/kg/day for serum ferritin more than 3,000 ng/mL. Do not regularly exceed an average daily dose of 50 mg/kg/day except when very intensive chelation is needed in persons who have completed growth. If ferritin concentrations decrease below 1,000 ng/mL, the risk of deferoxamine toxicity increases; consider lowering the total weekly dose in these cases.
Infants* and Children 1 to 2 years*: 25 to 35 mg/kg/dose subcutaneously over 8 to 24 hours for 5 to 7 days/week. Safe and effective use has not been established; however, some children with thalassemia younger than 3 years will exhibit signs of iron toxicity. Evaluate hepatic iron concentration in children that have required regular transfusions for at least 1 year; if elevated, deferoxamine therapy may be beneficial. Start at the lower end of the dosing range and increase the dose only if hepatic iron concentration or total body iron burden are still elevated.
Intravenous dosage:
Adults: 40 to 50 mg/kg/day IV over 8 to 12 hours for 5 to 7 days/week. Max: 60 mg/kg/day.
Children and Adolescents 3 to 17 years: 20 to 40 mg/kg/day IV over 8 to 12 hours for 5 to 7 days/week. Max: 40 mg/kg/day until growth (body weight and linear growth) has stopped.
Infants* and Children 1 to 2 years*: 25 to 35 mg/kg/dose IV over 8 to 12 hours for 5 to 7 days/week. Safe and effective use has not been established; however, some children with thalassemia younger than 3 years will exhibit signs of iron toxicity. Evaluate hepatic iron concentration in children that have required regular transfusions for at least 1 year; if elevated, deferoxamine therapy may be beneficial. Start at the lower end of the dosing range and increase the dose only if hepatic iron concentration or total body iron burden are still elevated.
Intramuscular dosage:
NOTE: Although intramuscular administration is FDA-approved, this route is not preferred and is typically not used in clinical practice.
Adults: 0.5 to 1 g IM once daily.
Children and Adolescents 3 to 17 years: 0.5 to 1 g IM once daily.
For the treatment of aluminum toxicity* in patients with chronic kidney disease on dialysis:
-for the diagnosis of aluminum toxicity using the deferoxamine test dose:
NOTE: A deferoxamine test should be performed if there are elevated serum aluminum levels (60 to 200 mcg/L), clinical signs and symptoms of aluminum toxicity, or prior to parathyroid surgery if the patient has had aluminum exposure. A deferoxamine test should not be performed if the serum aluminum level is more than 200 mcg/L to avoid deferoxamine-induced neurotoxicity. Deferoxamine should not be given until intensive dialysis (6 days per week) is performed and aluminum level has decreased to 200 mcg/L or less.
Intravenous dosage:
Adults: 5 mg/kg/dose by slow IV infusion over the last hour of dialysis session. Measure serum aluminum before deferoxamine infusion and 2 days later before the next dialysis session. The test is considered positive if the serum aluminum rise is at least 50 mcg/L.
Infants, Children, and Adolescents: 5 mg/kg/dose by slow IV infusion over the last hour of dialysis session. Measure serum aluminum before deferoxamine infusion and 2 days later before the next dialysis session. The test is considered positive if the serum aluminum rise is at least 50 mcg/L.
-for aluminum toxicity if serum aluminum concentration rise is 50 to 299 mcg/L AND there are no side effects after deferoxamine test dose:
Intravenous dosage:
Adults: 5 mg/kg/dose by slow IV infusion over the last hour of dialysis once weekly for 2 months. Then discontinue deferoxamine for one month and perform the deferoxamine-stimulation test again.
Infants, Children, and Adolescents: 5 mg/kg/dose by slow IV infusion over the last hour of dialysis once weekly for 2 months. Then discontinue deferoxamine for one month and perform the deferoxamine-stimulation test again.
Intraperitoneal dosage:
NOTE: The intraperitoneal route is preferred in patients receiving continuous peritoneal dialysis.
Adults: 5 mg/kg/dose intraperitoneally once weekly prior to the final exchange of the day once weekly for 2 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.
Infants, Children, and Adolescents: 5 mg/kg/dose intraperitoneally once weekly prior to the final exchange of the day once weekly for 2 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.
-for aluminum toxicity if serum aluminum concentration rise is 300 mcg/L or more OR side effects after deferoxamine test dose:
Intravenous dosage:
Adults: 5 mg/kg/dose by slow IV infusion over 1 hour once weekly 5 hours before dialysis for 4 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.
Infants, Children, and Adolescents: 5 mg/kg/dose by slow IV infusion over 1 hour once weekly 5 hours before dialysis for 4 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.
Intraperitoneal dosage:
NOTE: The intraperitoneal route is preferred in patients receiving continuous peritoneal dialysis.
Adults: 5 mg/kg/dose intraperitoneally once weekly prior to the final exchange of the day for 4 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.
Infants, Children, and Adolescents: 5 mg/kg/dose intraperitoneally once weekly prior to the final exchange of the day for 4 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.
Maximum Dosage Limits:
-Adults
Generally, 15 mg/kg/hour continuous IV infusion for acute iron toxicity; however, higher doses (up to 35 mg/kg/hour) have been safely used; FDA-approved maximum is 6 g/day; however, higher doses (16 to 20 g/day) are often needed. 60 mg/kg/day subcutaneously/IV/IM for chronic iron overload.
-Geriatric
Generally, 15 mg/kg/hour continuous IV infusion for acute iron toxicity; however, higher doses (up to 35 mg/kg/hour) have been safely used; FDA-approved maximum is 6 g/day; however, higher doses (16 to 20 g/day) are often needed. 60 mg/kg/day subcutaneously/IV/IM for chronic iron overload.
-Adolescents
Generally, 15 mg/kg/hour continuous IV infusion for acute iron toxicity; however, higher doses (up to 35 mg/kg/hour) have been safely used; FDA-approved maximum is 6 g/day; however, higher doses (16 to 20 g/day) are often needed. 50 mg/kg/day subcutaneously/IV/IM for chronic iron overload.
-Children
3 to 12 years: Generally, 15 mg/kg/hour continuous IV infusion for acute iron toxicity; however, higher doses (up to 35 mg/kg/hour) have been safely used; FDA-approved maximum is 6 g/day; however, higher doses (16 to 20 g/day) are often needed. 50 mg/kg/day subcutaneously/IV/IM for chronic iron overload.
1 to 2 years: Safety and efficacy have not been established; however, doses up to 15 to 35 mg/kg/hour continuous IV infusion for acute iron toxicity and 35 mg/kg/day IV/subcutaneously for chronic iron overload have been used off-label.
-Infants
Safety and efficacy have not been established; however, doses up to 15 to 35 mg/kg/hour continuous IV infusion for acute iron toxicity and 35 mg/kg/day IV/subcutaneously for chronic iron overload have been used off-label.
Patients with Hepatic Impairment Dosing
Specific guidelines are not available; for patients with hepatic impairment, dose selection should usually start at the low end of the dosing range.
Patients with Renal Impairment Dosing
Deferoxamine is contraindicated in patients with severe renal impairment or anuria or with other severe renal disease, since the drug and iron chelate (i.e., ferrioxamine) are eliminated primarily by the kidney. For patients with mild or moderate renal impairment, dose selection should usually start at the low end of the dosing range.
Intermittent hemodialysis
Both deferoxamine and ferrioxamine are removed by hemodialysis.
*non-FDA-approved indication
Ascorbic Acid, Vitamin C: (Major) Patients should be advised not to take ascorbic acid, vitamin C supplements along with deferoxamine chelation therapy unless such supplements are prescribed with the approval of their health care professional. Patients with iron overload usually become vitamin C deficient, probably because iron oxidizes the vitamin. Vitamin C can be a beneficial adjunct in iron chelation therapy because it facilitates iron chelation and iron complex excretion. As an adjuvant to iron chelation therapy (e.g., deferoxamine), vitamin C (in doses up to 200 mg/day for adults, 50 mg/day in children < 10 years of age or 100 mg/day in older children) may be given in divided doses, starting after an initial month of regular treatment with deferoxamine. However, higher doses of ascorbic acid, vitamin C can facilitate iron deposition, particularly in the heart tissue, causing cardiac decompensation. In patients with severe chronic iron overload, the concomitant use of deferoxamine with > 500 mg/day PO of vitamin C in adults has lead to impairment of cardiac function; the dysfunction was reversible when vitamin C was discontinued. The manufacturer of deferoxamine recommends certain precautions for the coadministration of vitamin C with deferoxamine. First, vitamin C supplements should not be given concurrently with deferoxamine in patients with heart failure. Secondly, in other patients, such supplementation should not be started until 1 month of regular treatment with deferoxamine, and should be given only to patients receiving regular deferoxamine treatments. Do not exceed vitamin C doses of 200 mg/day for adults, 50 mg/day in children < 10 years of age, or 100 mg/day in older children, given in divided doses. Clinically monitor all patients, especially the elderly, for signs or symptoms of decreased cardiac function.
Cyclosporine: (Moderate) Although not specifically studied, reduced serum concentrations of deferoxamine may occur in patients taking other CYP3A4 substrates such as cyclosporine. If these drugs are used together, monitor patients for a decrease in the effects of cyclosporine. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including cyclosporine, may increase the risk of acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and cyclosporine concomitantly.
Exagamglogene autotemcel: (Major) Avoid use of deferoxamine for 3 months after exagamglogene autotemcel infusion. Phlebotomy can be used instead of iron chelation, when appropriate.
Lovotibeglogene autotemcel: (Major) Avoid use of deferoxamine for 3 months after lovotibeglogene autotemcel infusion. Phlebotomy can be used instead of iron chelation, when appropriate.
Prochlorperazine: (Moderate) Concurrent treatment with deferoxamine and prochlorperazine may lead to a temporary impairment of consciousness. The mechanism of the interaction is not clear.
Vigabatrin: (Major) Vigabatrin should not be used with deferoxamine, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Ferric ions bind to the 3 hydroxamic groups of deferoxamine, creating ferrioxamine, a stable, water-soluble complex that is then readily excreted by the kidneys. Deferoxamine's affinity for iron is greater than that of other chelating agents, and administration of the drug does not appear to increase the excretion of electrolytes or other trace minerals. Deferoxamine readily chelates iron from ferritin and hemosiderin but not readily from transferrin; it does not combine with the iron from cytochromes and hemoglobin.
One gram of deferoxamine has the potential to chelate with 85 mg of iron, but the rate of iron excreted is dependent on pH, occurring most readily at an acidic pH. Deferoxamine complexes preferentially, if not exclusively, with the ferric ion. Concomitant administration of ascorbic acid with deferoxamine may increase the excretion of iron by promoting the conversion of ferrous ions to ferric ions. While enhancement of the renal elimination of iron is believed to be the predominant action of deferoxamine, some believe that deferoxamine may exert protective actions at the cellular level. The chelation of deferoxamine (and its subsequent conversion to ferrioxamine) may limit iron entry into cells because ferrioxamine is less permeable than deferoxamine. It is also possible that deferoxamine chelates intracellular extramitochondrial iron.
Aluminum excretion by the kidneys is also increased by deferoxamine. One gram of deferoxamine has the potential to bind 41 mg of aluminum.
Deferoxamine is administered intravenously, subcutaneously, and rarely, intramuscularly. The Vd of deferoxamine ranges from 0.6 to 1.33 L/kg. Ferrioxamine is formed when deferoxamine binds the ferric cation. This binding transforms deferoxamine from a straight chain structure to a stable octahedral compound with distinctly different pharmacokinetic characteristics. The volume of distribution of ferrioxamine (0.2 L/kg) is much smaller than deferoxamine suggesting that the molecule remains exclusively in the extracellular fluid. Deferoxamine is metabolized principally by plasma enzymes, but the pathways have not yet been defined. The chelate is readily soluble in water and passes easily through the kidney, giving the urine a characteristic reddish color. Some is also excreted in the feces via the bile. The elimination half-life of deferoxamine is approximately 20 to 30 minutes.
-Special Populations
Renal Impairment
Deferoxamine and the iron chelate are excreted primarily by the kidney. For patients with renal impairment, dose selection should usually start at the low end of the dosing range.