Deferoxamine (Monograph)

Brand name: Desferal
Drug class: Heavy Metal Antagonists
- Antidotes
ATC class: VO3AC01
VA class: AD300
Chemical name: N-[5-[3-[(5-aminopentyl)hydroxycarbamoyl]propionamido]pentyl]-3-[[5-(N-hydroxyacetamido)pentyl]carbamoyl]propionohydroxamic acid monomethanesulfonate (salt)
Molecular formula: C₂₅H₄₈N₆O₈.CH₄O₃S
CAS number: 138-14-7

Medically reviewed by Drugs.com on Mar 22, 2024. Written by ASHP.

Introduction

Heavy metal antagonist; chelating agent for iron and aluminum.

Uses for Deferoxamine

Acute Iron Intoxication

Adjunctive therapy for acute iron intoxication.

Not a substitute for standard measures generally used, including GI decontamination (e.g., induction of emesis, gastric lavage, whole-bowel irrigation), suction and maintenance of airway, correction of acidosis, and control of shock with IV fluids, blood, oxygen, and vasopressors.

Recommended for patients with severe manifestations of iron intoxication (e.g., metabolic acidosis, repetitive vomiting, lethargy, coma, seizures, hypotension, GI bleeding, signs of shock) or serum iron concentration >500 mcg/dL; less serious ingestions may be treated with supportive care alone.

Chronic Iron Overload

Treatment of chronic iron overload resulting from multiple transfusions in patients with thalassemia or other chronic anemias.

Long-term therapy may have beneficial effects on the liver (i.e., slow accumulation of hepatic iron, retard or eliminate progression of hepatic fibrosis).

In patients with thalassemia, long-term therapymay have beneficial effects on the heart (e.g., delay and/or prevent development of iron-associated cardiac disease, improve left ventricular function in patients with subclinical cardiac dysfunction, improve cardiac function in at least some patients with symptomatic cardiac disease ) and improve survival.

Initiate therapy early in the course of thalassemia (i.e., some clinicians recommend initiation of chelation therapy when serum ferritin concentrations reach 1000 ng/mL or child reaches the age of 3 years [see Pediatric Use under Cautions]) and monitor compliance closely; noncompliance with chelation regimen and failure to initiate therapy prior to development of irreversible tissue damage are associated with cardiac disease.

Aluminum Toxicity

Diagnosis or treatment of aluminum-associated neurotoxicity and/or bone abnormalities in patients with chronic renal failure undergoing dialysis^{† [off-label]}.

Hemochromatosis

Has been used with some success for treatment of iron overload secondary to primary hemochromatosis^{† [off-label]}. Phlebotomy is the method of choice for removal of excess iron; however, deferoxamine may be beneficial when phlebotomy is contraindicated.

Other Uses

Has been studied as a chelating agent for aluminum and its potential beneficial effects in patients with Alzheimer’s disease^{† [off-label]}; not currently recommended for this use since existing evidence to support such use is weak and long-term chelation therapy may be associated with potentially serious adverse effects.

Deferoxamine Dosage and Administration

Administration

Administer by IM injection, IV infusion, or sub-Q infusion.

Acute iron intoxication: Manufacturer states that IM injection is the preferred route of administration and should be used for all patients who are not in shock. Manufacturer recommends slowIV infusion only for patients with cardiovascular failure or shock, with switch to IM administration as soon as the patient’s clinical condition permits. However, most experts recommend IV infusion for intoxications requiring deferoxamine therapy (see Acute Iron Intoxication under Uses).

Chronic iron overload: Administer by slowsub-Q infusion. May administer IM.

Aluminum toxicity^{† [off-label]}: Generally administered by slow IV infusion. Has been administered IM or intraperitoneally^{† [off-label]}.

IV Administration

Administer by slow IV infusion.

Reconstitution

Reconstitute vial containing 500 mg of deferoxamine mesylate with 5 mL of sterile water for injection or vial containing 2 g of the drug with 20 mL of sterile water for injection to provide solution containing 95 mg/mL. Reconstituted solution is for single use only; discard unused portion.

Dilution

Add the required amount of reconstituted solution to 0.9% sodium chloride, 0.45% sodium chloride, dextrose injection, or lactated Ringer’s injection.

Rate of Administration

Rapid IV injection may result in flushing of the skin, generalized erythema, urticaria, hypotension, and shock. Maximum safe rate of administration not scientifically established.

Acute iron intoxication: Empiric maximum rate of 15 mg/kg per hour recommended for the first 1 g followed by a slower rate of ≤125 mg/hour if needed.

Aluminum toxicity: Infuse dose over 1 hour.

IM Administration

Reconstitution

Reconstitute vial containing 500 mg of deferoxamine mesylate with 2 mL of sterile water for injection or vial containing 2 g of the drug with 8 mL of sterile water for injection to provide solution containing 210 or 213 mg/mL, respectively. Reconstituted solution is for single use only; discard unused portion.

Sub-Q Administration

Administer by slow sub-Q infusion via a small, portable controlled-infusion device.

Reconstitution

Reconstitute vial containing 500 mg of deferoxamine mesylate with 5 mL of sterile water for injection or vial containing 2 g of the drug with 20 mL of sterile water for injection to provide solution containing 95 mg/mL. Reconstituted solution is for single use only; discard unused portion.

The reconstituted solution may be infused sub-Q undiluted.

Rate of Administration

Rate of infusion in patients with chronic iron overload must be individualized, but ranges from 20–40 mg/kg daily infused over 8–24 hours.

Most convenient to administer the drug overnight as an 8- to 12-hour sub-Q infusion. In some patients, iron excretion will be as high following an 8- to 12-hour infusion as the same dose administered over a 24-hour period.

Dosage

Available as deferoxamine mesylate; dosage expressed in terms of the salt.

Pediatric Patients

Acute Iron Intoxication

IV or IM

Optimal dosage and duration of therapy not established. Consultation with poison control expert recommended in severe intoxications.

Manufacturer recommends 1 g initially; may be followed by 500 mg every 4 hours for 2 doses. Subsequent doses of 500 mg may be administered every 4–12 hours depending on clinical response (maximum 6 g in 24 hours).

Alternatively, initial dose of 20 mg/kg or 600 mg/m² followed by 10 mg/kg or 300 mg/m² at 4-hour intervals for 2 doses. Subsequent doses of 10 mg/kg or 300 mg/m²may be administered every 4–12 hours as needed.

Chronic Iron Overload

IM

Usual IM dosage is 0.5–1 g daily. In addition, administer 2 g of the drug by slowIV infusion with, but separate from, each unit of blood transfused (not to exceed 6 g with transfusion, even if ≥3 units of blood or packed RBCs transfused).

Sub-Q

Usual dosage is 1–2 g (20–40 mg/kg) infused daily.

Aluminum Toxicity†

Diagnosis† in Patients with CKD

IV

Test dose of 5 mg/kg (by slowIV infusion during the last hour of a dialysis session) in patients with clinical signs and symptoms of aluminum toxicity, with serum aluminum concentrations of 60–200 mcg/L, or prior to parathyroidectomy if patient has had aluminum exposure for ≥4 months. Test is positive for aluminum toxicity if the increase in serum aluminum above baseline is ≥50 mcg/L 2 days later at the start of the next dialysis session.

If baseline serum aluminum concentration is >200 mcg/L, institute measures (i.e., discontinue all aluminum intake, perform dialysis 6 days per week) to reduce aluminum concentration to <200 mcg/L (to reduce risk of neurotoxicity) prior to administering deferoxamine test dose.

Treatment† in Patients with CKD

IV

Deferoxamine treatment is indicated in symptomatic patients with serum aluminum concentrations >60 but <200 mcg/L or with an increase in serum aluminum concentration of ≥50 mcg/L following deferoxamine test dose. To avoid deferoxamine-induced neurotoxicity in patients with serum aluminum concentrations >200 mcg/L, delay initiation of deferoxamine therapy until predialysis serum aluminum concentration is reduced to <200 mcg/L (e.g., by intensive dialysis [6 days per week with high-flux membrane; dialysate aluminum concentration <5 mcg/L], elimination of other sources of aluminum intake).

Deferoxamine treatment considered optional in asymptomatic children receiving maintenance hemodialysis with serum aluminum concentrations of 60–200 mcg/L unless desired serum aluminum concentration is not achieved with discontinuance of aluminum-containing gels and intensive dialysis.

Treatment recommendations are based on results of deferoxamine diagnostic testing (see table 1).

Adults

Acute Iron Intoxication

IV or IM

Optimal dosage and duration of therapy not established. Consultation with poison control expert recommended in severe intoxications.

Manufacturer recommends 1 g initially; may be followed by 500 mg every 4 hours for 2 doses. Subsequent doses of 500 mg may be administered every 4–12 hours depending on clinical response (maximum 6 g in 24 hours).

Chronic Iron Overload

IM

Usual IM dosage is 0.5–1 g daily. In addition, administer 2 g of the drug by slowIV infusion with, but separate from, each unit of blood transfused (not to exceed 6 g with transfusion, even if ≥3 units of blood or packed RBCs transfused).

Sub-Q

Usual dosage is 1–2 g (20–40 mg/kg) infused daily.

Aluminum Toxicity†

Diagnosis† in Patients with CKD

IV

Test dose of 5 mg/kg (by slow IV infusion during the last hour of a dialysis session) in patients with clinical signs and symptoms of aluminum toxicity, with serum aluminum concentrations of 60–200 mcg/L, or prior to parathyroid surgery if patient has had aluminum exposure. Test is positive for aluminum toxicity if the increase in serum aluminum above baseline is ≥50 mcg/L 2 days later at the start of the next dialysis session.

If baseline serum aluminum concentration is >200 mcg/L, institute measures (i.e., discontinue all aluminum intake, perform dialysis 6 days per week) to reduce aluminum concentration to <200 mcg/L (to reduce risk of neurotoxicity) prior to administering deferoxamine test dose.

Treatment† in Patients with CKD

IV

Deferoxamine treatment is indicated in symptomatic patients with serum aluminum concentrations >60 but <200 mcg/L or with an increase in serum aluminum concentration of ≥50 mcg/L following deferoxamine test dose. To avoid deferoxamine-induced neurotoxicity in patients with serum aluminum concentrations >200 mcg/L, delay initiation of deferoxamine therapy until predialysis serum aluminum concentration is reduced to <200 mcg/L (e.g., by intensive dialysis [6 days per week with high-flux membrane; dialysate aluminum concentration <5 mcg/L], elimination of other sources of aluminum intake).

Treatment recommendations are based on results of deferoxamine diagnostic testing (see table 2).

Prescribing Limits

Pediatric Patients

Acute Iron Intoxication

IV or IM

Maximum 6 g daily recommended by manufacturer. Some experts state that larger dosages may be required in severe intoxications.

Chronic Iron Overload

IM

Maximum 1 g daily in the absence of transfusion, or 6 g daily with transfusion (even if ≥3 units of blood or packed RBCs transfused).

Adults

Acute Iron Intoxication

IV or IM

Maximum 6 g daily recommended by manufacturer. Some experts state that larger dosages may be required in severe intoxications.

Chronic Iron Overload

IM

Maximum 1 g daily in the absence of transfusion, or 6 g daily with transfusion (even if ≥3 units of blood or packed RBCs transfused).

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time. (See Renal Impairment under Cautions.)

Geriatric Patients

Select dosage with caution because of age-related decreases in renal, hepatic, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Deferoxamine

Contraindications

• Severe renal disease or anuria (although may be used for diagnosis or treatment of aluminum toxicity in patients with chronic renal failure undergoing dialysis^† [see Renal Impairment under Cautions]).

Warnings/Precautions

Warnings

Ocular and Otic Effects

Risk of ocular toxicity including cataracts following prolonged administration; decreased visual acuity (i.e., blurred vision, visual loss); visual field defects (e.g., scotoma, loss of central or peripheral vision); impaired color and night vision; optic neuritis; corneal opacities; and retinal pigmentary abnormalities.

Risk of ototoxicity including tinnitus, hearing loss (e.g., high frequency sensorineural hearing loss), audiogram abnormalities (with or without clinical hearing loss), and occasionally deafness.

High dosages, prolonged therapy, and/or low iron stores increase risk for development of ocular toxicity and ototoxicity.

Early detection of abnormalities important to minimize risk of irreversible toxicity. Monitor patients regularly for body iron burden and hemoglobin. Periodic ophthalmologic examinations (e.g., visual acuity tests, slit-lamp examinations, funduscopy) and auditory testing (e.g., otolaryngologic and audiometric examinations) recommended in patients receiving prolonged therapy. Some clinicians recommend complete ophthalmologic examinations, studies of visual evoked potentials, and audiometry every 3 months in patients treated for chronic iron overload, particularly when dosages >50 mg/kg daily are employed.

Immediatediscontinuance of deferoxamine generally results in reversal of ocular and otic effects. Ocular and otic effects may partially or completely resolve following discontinuance of the drug. In some cases, ocular and otic effects may persist. If hearing loss persists, a hearing aid may be necessary. Deferoxamine therapy usually can be resumed, if necessary, at a reduced dosage with close electroretinographic monitoring.

Effects on Bone Development and Growth

Risk of growth retardation in children receiving long-term deferoxamine therapy if excessive dosage is given or therapy is initiated prior to accumulation of a clinically important iron load. (See Pediatric Use under Cautions.)

Changes may include abnormalities in metaphyseal growth plate, vertebral abnormalities, and rickets- or scurvy-like changes in long bones.

Growth velocity may partially return to pretreatment rates following dosage reduction.

Adult Respiratory Distress Syndrome (ARDS)

Risk of ARDS-like condition (sometimes fatal) with dyspnea, cyanosis, and/or interstitial infiltrates.

Reported in both adult and pediatric patients receiving excessively high dosages (including total and cumulative doses) and prolonged continuous IV therapy (>24 hours).

Sensitivity Reactions

Hypersensitivity Reactions

Generalized rash, urticaria, angioedema, and anaphylactic reaction (with or without shock) reported. Local injection site reactions may be accompanied by systemic allergic reactions.

Following rapid IV injection, flushing of the skin, generalized erythema, urticaria, hypotension, and shock may occur; administer IM or by slowIV or sub-Q infusion to avoid these reactions. (See IV Administration: Rate of Administration, under Dosage and Administration).

Allergic-type reactions, such as cutaneous wheal formation, pruritus, rash, and anaphylactoid reactions, reported in patients receiving long-term therapy for chronic iron overload.

General Precautions

Susceptibility to Infection

Increased susceptibility to Yersinia enterocolitica and Y. pseudotuberculosis infections reported, potentially resulting in generalized infections.

If Y. enterocolitica or Y. pseudotuberculosis infection is confirmed or strongly suspected, discontinue the drug until the infection resolves and initiate appropriate anti-infective therapy.

Fungal infections (e.g., mucormycosis, including infections caused by Rhizopus) reported rarely (sometimes fatal).

If signs or symptoms suggestive of mucormycosis occur, discontinue the drug, perform mycologic tests, and initiate appropriate anti-infective therapy.

Cardiovascular Effects

Hypotension, with associated tachycardia, reported following rapid IV administration of relatively large dosages.

BP usually returns to normal ≤1 hour following discontinuance of the infusion.

If hypotension occurs, discontinue deferoxamine and reinitiate at a slower infusion rate once BP returns to normal; however, exercise caution in attributing the hypotension to the drug in acute iron intoxication, especially when drug therapy is considered urgent.

Increased risk of impaired cardiovascular function in patients with severe chronic iron overload receiving deferoxamine and high dosages of ascorbic acid. (See Interactions.)

Neurologic Effects

Potential for exacerbation of neurologic dysfunction including seizures in patients with aluminum-related encephalopathy, probably due to an acute increase in circulating aluminum. Risk of acute, potentially fatal neurotoxicity in those with serum aluminum concentrations >200 mcg/L; delay initiation of deferoxamine until predialysis serum aluminum concentrations are reduced to <200 mcg/L by other means (see Aluminum Toxicity, under Pediatric Patients and also under Adults, in Dosage and Administration).

May precipitate the onset of dialysis dementia.

Hypocalcemia

Treatment with deferoxamine in the presence of aluminum overload may result in decreased serum calcium concentrations and aggravate hyperparathyroidism.

Pyelonephritis

Urinary excretion of parenterally administered iron has been reported to exacerbate latent pyelonephritis; this also may occur with deferoxamine therapy. Use deferoxamine with caution in patients with pyelonephritis.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether deferoxamine is distributed into milk. Use caution in nursing women.

Pediatric Use

Safety and efficacy not established in children <3 years of age.

Iron mobilization with deferoxamine is relatively poor in children <3 years of age with relatively little iron overload; drug should generally not be given to such patients unless mobilization of ≥1 mg of iron daily can be demonstrated.

Monitor growth and body weight of children receiving long-term therapy (e.g., those with thalassemia) every 3 months, since growth retardation reported; document measurements on charts to detect early changes in growth patterns and establish appropriate plan for further treatment.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.

Postmarketing experience suggests possible increased risk of ocular disorders (color blindness, maculopathy, scotoma) and ototoxicity (deafness, hearing loss) in geriatric patients. Unclear whether ocular disorders were dose related.

Renal Impairment

Manufacturer states that deferoxamine is contraindicated in severe renal disease or anuria, since deferoxamine and ferrioxamine are excreted principally in urine; however, may be used for diagnosis or treatment of aluminum toxicity in patients with chronic renal failure undergoing dialysis^†.

When used for treatment of aluminum toxicity, use in a manner that maximizes removal of chelated aluminum and iron (e.g., 3 or 4 dialysis sessions scheduled between doses, appropriate intervals between deferoxamine administration and next dialysis session, use of highly permeable dialyzer membrane) (see Aluminum Toxicity, under Pediatric Patients and also under Adults, in Dosage and Administration).

Common Adverse Effects

Data regarding frequency of adverse events are lacking.

Localized pain, irritation, burning, swelling, and induration may occur at the injection site following IV or sub-Q administration.

Adverse ocular and otic effects (see Warnings), abdominal discomfort, diarrhea, nausea, vomiting, leg cramps, tachycardia, and fever reported.

Drug Interactions

Specific Drugs and Laboratory Tests

Deferoxamine Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from the GI tract in the presence of intact mucosa; however, absorption may occur in patients with acute iron intoxication.

Distribution

Extent

Widely distributed into body tissues and fluids.

Elimination

Metabolism

Metabolized principally by plasma enzymes, but exact pathways remain to be determined.

Elimination Route

Excreted principally in urine as unchanged drug and ferrioxamine (gives urine a characteristic reddish color); ferrioxamine also excreted in feces via bile.

Deferoxamine is removed by dialysis. Deferoxamine-iron and deferoxamine-aluminum chelates also removed by dialysis (see Renal Impairment under Cautions).

Half-life

20 minutes.

Stability

Storage

Parenteral

Powder for Injection

≤25°C.

Reconstituted solution is stable for 1 week at room temperature. However, the manufacturer recommends use within 3 hours of reconstitution for microbiologic safety.

Store solutions prepared under aseptic conditions for ≤24 hours at room temperature; avoid refrigeration. Do not use turbid solutions.

Compatibility

Parenteral

Solution Compatibility

Actions

• Chelates iron by binding ferric ions to the 3 hydroxamic groups of the molecule and forming a stable complex, ferrioxamine, that prevents iron from entering into further chemical reactions.

• A hexadentate ligand with high binding affinity for iron in a 1:1 ratio.

• Theoretically, 1 g of deferoxamine mesylate is capable of sequestering 85 mg of iron (as the ferric ion); however, the rate of complex formation appears to be pH dependent (most rapid at acid pH).

• Main effect is probably on loosely bound stored iron; in vitro studies have shown that deferoxamine removes iron from ferritin, hemosiderin, and, to a lesser extent, transferrin, but not from cytochromes or hemoglobin.

• Also chelates aluminum and increases its excretion by the kidneys and/or removal by dialysis.

Advice to Patients

• Potential for drug to cause nervous system effects (e.g., dizziness) or impairment of vision or hearing; avoid driving or operating machinery if such effects occur.

• Advise patients that therapy may cause a reddish discoloration of urine.

• Importance of compliance with long-term chelation therapy for chronic iron overload.

• Importance of periodic ophthalmologic examinations and auditory testing during long-term therapy.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary (e.g., vitamin C) and herbal supplements, as well as any concomitant illnesses.

• Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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