Desferal

Generic Name: Deferoxamine Mesylate
Class: Heavy Metal Antagonists
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

Introduction

Heavy metal antagonist; chelating agent for iron118 194 b and aluminum.195 196 197 b

Uses for Desferal

Acute Iron Intoxication

Adjunctive therapy for acute iron intoxication.118 b

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.118 202 b

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.202 203 204 205 b

Chronic Iron Overload

Treatment of chronic iron overload resulting from multiple transfusions in patients with thalassemia or other chronic anemias.118 194 b

Slideshow: The Ferocity of Chemotherapy - Does The End Justify The Means?

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

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,100 101 128 129 130 132 133 134 improve left ventricular function in patients with subclinical cardiac dysfunction,101 132 improve cardiac function in at least some patients with symptomatic cardiac disease102 ) and improve survival.129 133 134 135

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 years133 [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.129 130 133

Aluminum Toxicity

Diagnosis119 127 195 196 200 201 or treatment of aluminum-associated neurotoxicity and/or bone abnormalities in patients with chronic renal failure undergoing dialysis.104 105 106 107 108 109 126 195 196 197 200 201

Hemochromatosis

Has been used with some success for treatment of iron overload secondary to primary hemochromatosis.b Phlebotomy is the method of choice for removal of excess iron;118 b however, deferoxamine may be beneficial when phlebotomy is contraindicated.b

Other Uses

Has been studied as a chelating agent for aluminum and its potential beneficial effects in patients with Alzheimer’s disease;142 152 153 154 155 156 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.142 153

Desferal Dosage and Administration

Administration

Administer by IM injection, IV infusion, or sub-Q infusion.118 b

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.118 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.118 However, most experts recommend IV infusion for intoxications requiring deferoxamine therapy (see Acute Iron Intoxication under Uses).202 203 204 205

Chronic iron overload: Administer by slowsub-Q infusion.118 b May administer IM.118 b

Aluminum toxicity: Generally administered by slow IV infusion.126 195 196 200 201 Has been administered IM or intraperitoneally.107 108 109 149 200 201

IV Administration

Administer by slow IV infusion.118 b

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.118 Reconstituted solution is for single use only;118 discard unused portion.118

Dilution

Add the required amount of reconstituted solution to 0.9% sodium chloride, 0.45% sodium chloride, dextrose injection, or lactated Ringer’s injection.118

Rate of Administration

Rapid IV injection may result in flushing of the skin, generalized erythema, urticaria, hypotension, and shock.118 b Maximum safe rate of administration not scientifically established.159 203

Acute iron intoxication: Empiric maximum rate of 15 mg/kg per hour recommended for the first 1 g118 159 167 169 176 followed by a slower rate of ≤125 mg/hour if needed.118

Aluminum toxicity: Infuse dose over 1 hour.200 201

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.118 Reconstituted solution is for single use only; discard unused portion.118

Sub-Q Administration

Administer by slow sub-Q infusion via a small, portable controlled-infusion device.118

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.118 Reconstituted solution is for single use only; discard unused portion.118

The reconstituted solution may be infused sub-Q undiluted.b

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.118 b

Most convenient to administer the drug overnight as an 8- to 12-hour sub-Q infusion.b 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.118 b

Dosage

Available as deferoxamine mesylate; dosage expressed in terms of the salt.118

Pediatric Patients

Acute Iron Intoxication
IV or IM

Optimal dosage and duration of therapy not established.202 203 204 205 Consultation with poison control expert recommended in severe intoxications.204 205

Manufacturer recommends 1 g initially; may be followed by 500 mg every 4 hours for 2 doses.118 Subsequent doses of 500 mg may be administered every 4–12 hours depending on clinical response (maximum 6 g in 24 hours).118

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.b Subsequent doses of 10 mg/kg or 300 mg/m2may be administered every 4–12 hours as needed.b

Chronic Iron Overload
IM

Usual IM dosage is 0.5–1 g daily.118 b 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).118

Sub-Q

Usual dosage is 1–2 g (20–40 mg/kg) infused daily.118 b

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.201 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.201

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.201

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.201 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).201

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.201

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

Table 1.

Deferoxamine Test Results

Deferoxamine Treatment Regimen

Occurrence of adverse neurologic effects or an increase in serum aluminum concentration of ≥300 mcg/L above baseline:

5 mg/kg infused over 1 hour once weekly for 4 months;201 administer the weekly dose 5 hours prior to high-efficiency hemodialysis to ensure rapid removal of aluminum-chelator complex201

 

Following 4 months of therapy, discontinue deferoxamine, repeat the diagnostic test dose of deferoxamine following a 1-month washout period, and assess test results201

No adverse neurologic effects and an increase in serum aluminum concentration of 50–299 mcg/L above baseline:

5 mg/kg once weekly for 2 months;201 infuse the weekly dose over the last hour of a hemodialysis session; perform high-efficiency hemodialysis 44 hours later201

 

Following 2 months of therapy, discontinue deferoxamine, repeat the diagnostic test dose of deferoxamine following a 1-month washout period, and assess test results201

No adverse neurologic effects and an increase in serum aluminum concentration of <50 mcg/L above baseline:

Repeat diagnostic test dose of deferoxamine in 1 month and (if same result obtained) again after 4 months;201 if serum aluminum concentration remains <50 mcg/L above baseline, no further therapy required201

Adults

Acute Iron Intoxication
IV or IM

Optimal dosage and duration of therapy not established.202 203 204 205 Consultation with poison control expert recommended in severe intoxications.204 205

Manufacturer recommends 1 g initially; may be followed by 500 mg every 4 hours for 2 doses.118 b Subsequent doses of 500 mg may be administered every 4–12 hours depending on clinical response (maximum 6 g in 24 hours).118 b

Chronic Iron Overload
IM

Usual IM dosage is 0.5–1 g daily.118 b 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).118

Sub-Q

Usual dosage is 1–2 g (20–40 mg/kg) infused daily.118 b

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.200 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.200

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.200

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.200 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).200

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

Table 2.

Deferoxamine Test Results

Deferoxamine Treatment Regimen

Occurrence of adverse neurologic effects or an increase in serum aluminum concentration of ≥300 mcg/L above baseline:

5 mg/kg infused over 1 hour once weekly for 4 months;200 administer the weekly dose 5 hours prior to high-efficiency hemodialysis to ensure rapid removal of aluminum-chelator complex200

Following 4 months of therapy, discontinue deferoxamine, repeat the diagnostic test dose of deferoxamine following a 1-month washout period, and assess test results200

No adverse neurologic effects and an increase in serum aluminum concentration of 50–299 mcg/L above baseline:

5 mg/kg once weekly for 2 months;200 infuse the weekly dose over the last hour of a hemodialysis session; perform high-efficiency hemodialysis 44 hours later200

Following 2 months of therapy, discontinue deferoxamine, repeat the diagnostic test dose of deferoxamine following a 1-month washout period, and assess test results200

No adverse neurologic effects and an increase in serum aluminum concentration of <50 mcg/L above baseline:

Repeat diagnostic test dose of deferoxamine in 1 month and (if same result obtained) again after 4 months;200 if serum aluminum concentration remains <50 mcg/L above baseline, no further therapy required200

Prescribing Limits

Pediatric Patients

Acute Iron Intoxication
IV or IM

Maximum 6 g daily recommended by manufacturer.118 Some experts state that larger dosages may be required in severe intoxications.202 203 204

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).118

Adults

Acute Iron Intoxication
IV or IM

Maximum 6 g daily recommended by manufacturer.118 Some experts state that larger dosages may be required in severe intoxications.202 203 204

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).118

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.118

Renal Impairment

No specific dosage recommendations at this time.118 (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.118

Cautions for Desferal

Contraindications

Warnings/Precautions

Warnings

Ocular and Otic Effects

Risk of ocular toxicity including cataracts following prolonged administration;118 b decreased visual acuity (i.e., blurred vision, visual loss);112 116 118 119 120 133 visual field defects (e.g., scotoma, loss of central or peripheral vision);112 114 115 116 118 133 160 impaired color and night vision;112 114 115 116 118 119 120 133 160 161 optic neuritis;115 116 118 133 corneal opacities;118 and retinal pigmentary abnormalities.112 115 116 118 133 160

Risk of ototoxicity including tinnitus,118 hearing loss (e.g., high frequency sensorineural hearing loss),116 117 118 160 162 audiogram abnormalities (with or without clinical hearing loss), and occasionally deafness.116 117 118 120 133 159 160 162

High dosages, prolonged therapy, and/or low iron stores increase risk for development of ocular toxicity118 159 160 161 and ototoxicity.118 159 162 164

Early detection of abnormalities important to minimize risk of irreversible toxicity.118 b Monitor patients regularly for body iron burden and hemoglobin.162 b 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.118 162 b 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.116

Immediatediscontinuance of deferoxamine generally results in reversal of ocular and otic effects.118 Ocular and otic effects may partially or completely resolve following discontinuance of the drug.116 117 In some cases, ocular and otic effects may persist.112 113 114 115 116 120 133 159 If hearing loss persists, a hearing aid may be necessary.116 159 Deferoxamine therapy usually can be resumed, if necessary, at a reduced dosage with close electroretinographic monitoring.133

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.118 133 178 179 183 185 (See Pediatric Use under Cautions.)

Changes may include abnormalities in metaphyseal growth plate,118 183 185 vertebral abnormalities,133 181 182 185 and rickets- or scurvy-like changes in long bones.133 184

Growth velocity may partially return to pretreatment rates following dosage reduction.118 133 186

Adult Respiratory Distress Syndrome (ARDS)

Risk of ARDS-like condition (sometimes fatal) with dyspnea, cyanosis, and/or interstitial infiltrates.118 133 159 165 170 171 172 173

Reported in both adult and pediatric patients118 133 159 165 170 171 172 173 receiving excessively high dosages (including total and cumulative doses) and prolonged continuous IV therapy (>24 hours).118 133 159 165 167 173 202 203

Sensitivity Reactions

Hypersensitivity Reactions

Generalized rash, urticaria, angioedema, and anaphylactic reaction (with or without shock) reported.118 Local injection site reactions may be accompanied by systemic allergic reactions.118

Following rapid IV injection, flushing of the skin, generalized erythema, urticaria, hypotension, and shock may occur;118 b administer IM or by slowIV or sub-Q infusion to avoid these reactions.118 b (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.b

General Precautions

Susceptibility to Infection

Increased susceptibility to Yersinia enterocolitica and Y. pseudotuberculosis infections reported, potentially resulting in generalized infections.118 b

If Y. enterocolitica or Y. pseudotuberculosis infection is confirmed or strongly suspected, discontinue the drug until the infection resolves118 b and initiate appropriate anti-infective therapy.b

Fungal infections (e.g., mucormycosis, including infections caused by Rhizopus) reported rarely (sometimes fatal).118 200 201 b

If signs or symptoms suggestive of mucormycosis occur, discontinue the drug, perform mycologic tests, and initiate appropriate anti-infective therapy.118 b

Cardiovascular Effects

Hypotension, with associated tachycardia, reported following rapid IV administration of relatively large dosages.118 159 160 174 177

BP usually returns to normal ≤1 hour following discontinuance of the infusion.160

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.160

Increased risk of impaired cardiovascular function in patients with severe chronic iron overload receiving deferoxamine and high dosages of ascorbic acid.118 (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.118 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).200 201

May precipitate the onset of dialysis dementia.118

Hypocalcemia

Treatment with deferoxamine in the presence of aluminum overload may result in decreased serum calcium concentrations and aggravate hyperparathyroidism.118

Pyelonephritis

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

Specific Populations

Pregnancy

Category C.118 b

Lactation

Not known whether deferoxamine is distributed into milk.118 Use caution in nursing women.118

Pediatric Use

Safety and efficacy not established in children <3 years of age.118

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.118

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.118 133 181

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.118

Postmarketing experience suggests possible increased risk of ocular disorders (color blindness, maculopathy, scotoma) and ototoxicity (deafness, hearing loss) in geriatric patients.118 Unclear whether ocular disorders were dose related.118

Renal Impairment

Manufacturer states that deferoxamine is contraindicated in severe renal disease or anuria, since deferoxamine and ferrioxamine are excreted principally in urine;118 b however, may be used for diagnosis119 127 195 196 200 201 or treatment of aluminum toxicity in patients with chronic renal failure undergoing dialysis.104 105 106 107 108 109 126 195 196 197 200 201

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).200 201

Common Adverse Effects

Data regarding frequency of adverse events are lacking.118

Localized pain, irritation, burning, swelling, and induration may occur at the injection site following IV or sub-Q administration.118 b

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

Interactions for Desferal

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Ascorbic acid

Increases availability of iron for chelation118

Potential for impaired cardiovascular function following concomitant therapy with deferoxamine and high dosages of ascorbic acid (i.e., >500 mg daily in adults) in patients with severe chronic iron overload; cardiovascular dysfunction reversible following discontinuance of ascorbic acid118 b

Avoid ascorbic acid supplements in deferoxamine-treated patients with cardiac failure118

If concomitant therapy is warranted, initiate ascorbic acid only following 1 month of regular deferoxamine therapy; avoid ascorbic acid dosages of >200 mg daily (given in divided doses) in adults; in children <10 years of age, ascorbic acid 50 mg daily is recommended; for children ≥10 years of age, 100 mg daily is recommended118

Clinical monitoring of cardiac function advised in patients receiving concomitant therapy118

Prochlorperazine

Possible synergistic increase in adverse neurologic effects of the drugs; potential for temporary loss of consciousness 118 188

Gallium Ga 67

Imaging results may be distorted because of rapid urinary excretion of deferoxamine-bound gallium Ga 67118 189 190 191

Discontinuance of deferoxamine 48 hours prior to scintigraphy is advised118

Desferal 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.b

Distribution

Extent

Widely distributed into body tissues and fluids.b

Elimination

Metabolism

Metabolized principally by plasma enzymes, but exact pathways remain to be determined.118

Elimination Route

Excreted principally in urine as unchanged drug and ferrioxamine (gives urine a characteristic reddish color);118 b ferrioxamine also excreted in feces via bile.118

Deferoxamine is removed by dialysis.118 195 Deferoxamine-iron and deferoxamine-aluminum chelates also removed by dialysis (see Renal Impairment under Cautions).195 200 201 b

Half-life

20 minutes.198 199

Stability

Storage

Parenteral

Powder for Injection

≤25°C.118 b

Reconstituted solution is stable for 1 week at room temperature.b However, the manufacturer recommends use within 3 hours of reconstitution for microbiologic safety.118 b

Store solutions prepared under aseptic conditions for ≤24 hours at room temperature; avoid refrigeration.118 b Do not use turbid solutions.118 b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible118 b

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

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.118 b

  • A hexadentate ligand with high binding affinity for iron in a 1:1 ratio.198

  • Theoretically, 1 g of deferoxamine mesylate is capable of sequestering 85 mg of iron (as the ferric ion);118 b however, the rate of complex formation appears to be pH dependent (most rapid at acid pH).b

  • 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.b

  • Also chelates aluminum104 105 106 107 108 109 and increases its excretion by the kidneys106 and/or removal by dialysis.104 105 106 107 108 109

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.118

  • Advise patients that therapy may cause a reddish discoloration of urine.118

  • Importance of compliance with long-term chelation therapy for chronic iron overload.129 130 133

  • Importance of periodic ophthalmologic examinations and auditory testing during long-term therapy.118 162 b

  • 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.118

  • Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.118

  • Importance of informing patients of other important precautionary information.118 (See Cautions.)

Preparations

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

Deferoxamine Mesylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

500 mg and 2 g

Deferoxamine Mesylate for Injection

Desferal

Novartis

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

100. Wolfe L, Olivieri N, Sallan D et al. Prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major. N Engl J Med. 1986; 312:1600-3.

101. Freeman AP, Giles RW, Berdoukas VA et al. Early left ventricular dysfunction and chelation therapy in thalassemia major. Ann Intern Med. 1983; 99:450-4. [IDIS 176699] [PubMed 6625375]

102. Marcus RE, Davies SC, Bantock HM et al. Desferrioxamine to improve cardiac function in iron-overloaded patients with thalassaemia major. Lancet. 1984; 1:392-3. [IDIS 181610] [PubMed 6141447]

103. Anon. High-dose chelation therapy in thalassaemia. Lancet. 1984; 1:373-4. [PubMed 6141429]

104. Ackrill P, Ralston AJ, Day JP et al. Successful removal of aluminum from patients with dialysis encephalopathy. Lancet. 1980; 2:692-3. [IDIS 125335] [PubMed 6106803]

105. Brown DJ, Dawborn JK, Ham KN et al. Treatment of dialysis osteomalacia with desferrioxamine. Lancet. 1982; 2:343-5. [IDIS 155074] [PubMed 6124756]

106. Malluche HH, Smith AJ, Abreo K et al. The use of deferoxamine in the management of aluminum accumulation in bone in patients with renal failure. N Engl J Med. 1984; 311:140-4. [IDIS 187536] [PubMed 6377067]

107. Payton CD, Junor BJR, Fell GS. Successful treatment of aluminum encephalopathy by intraperitoneal desferrioxamine. Lancet. 1984; 1:1132-3. [IDIS 185483] [PubMed 6144870]

108. Andreoli SP, Dunn D, DeMyer W et al. Intraperitoneal deferoxamine therapy for aluminum intoxication in a child undergoing continuous ambulatory peritoneal dialysis. J Pediatr. 1985; 107:760-3. [IDIS 209623] [PubMed 3932629]

109. Freundlich M, Zilleruelo G, Faugere MC et al. Treatment of aluminum toxicity in infantile uremia with deferoxamine. J Pediatr. 1986; 109:140-3. [IDIS 218528] [PubMed 3723235]

110. Miller KB, Rosenwasser LJ, Bessette JM et al. Rapid desensitization for desferrioxamine anaphylactic reaction. Lancet. 1981; 1:1059.

111. Bousquet J, Navarro M, Robert G et al. Rapid desensitization for desferrioxamine anaphylactoid reactions. Lancet. 1983; 2:859-60. [IDIS 176866] [PubMed 6137689]

112. Davies SC, Marcus RE, Hungerford JL et al. Ocular toxicity of high-dose intravenous desferrioxamine. Lancet. 1983; 2:181-4. [PubMed 6135026]

113. Borgna-Pignatti C, De Stefano P, Broglia AM. Visual loss in patients on high-dose subcutaneous desferrioxamine. Lancet. 1984; 1:681. [IDIS 183172] [PubMed 6142370]

114. Rubinstein M, Dupont P, Doppee JP et al. Ocular toxicity of desferrioxamine. Lancet. 1985; 1:817-8. [IDIS 198851] [PubMed 2858690]

115. Lakhanpal V, Schocket SS, Jiji R. Deferoxamine (Desferal)-induced toxic retinal pigmentary degeneration and presumed optic neuropathy. Ophthalmology. 1984; 91:443-51. [PubMed 6739047]

116. Olivieri NF, Buncic JR, Chew E et al. Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions. N Engl J Med. 1986; 314:869-73. [IDIS 213050] [PubMed 3485251]

117. Guerin A, London G, Marchais S et al. Acute deafness and desferrioxamine. Lancet. 1985; 2:39-40. [IDIS 202046] [PubMed 2861480]

118. Novartis. Desferal(deferoxamine mesylate) for injection prescribing information. East Hanover, NJ; 2007 Nov. From DailyMed website ().

119. Bene C, Manzler D, Kranias G. Irreversible ocular toxicity from single “challenge” dose of deferoxamine. Clin Nephrol. 1989; 31:45-8. [PubMed 2783668]

120. Cases A, Kelly J, Sabater J et al. Acute visual and auditory neurotoxicity in patients with end-stage renal disease receiving desferrioxamine. Clin Nephrol. 1988; 29:176-8. [PubMed 3365862]

121. Goodill JJ, Abuelo JG. Mucormycosis—a new risk of deferoxamine therapy in dialysis patients with aluminum or iron overload? N Engl J Med. 1987; 317:54. Letter.

122. Veis JH, Contiguglia R, Klein M et al. Mucormycosis in deferoxamine-treated patients on dialysis. Ann Intern Med. 1987; 107:258. [IDIS 233231] [PubMed 3605912]

123. Sane A, Manzi S, Perfect J et al. Deferoxamine treatment as a risk factor for zygomycete infection. J Infect Dis. 1989; 159:151-2. [IDIS 250860] [PubMed 2909637]

124. Windus DW, Stokes TJ, Julian BA et al. Fatal rhizopus infections in hemodialysis patients receiving deferoxamine. Ann Intern Med. 1987; 107:678-80. [IDIS 235743] [PubMed 3662280]

125. Gallant T, Freedman MH, Vellend H et al. Yersinia sepsis in patients with iron overload treated with deferoxamine. N Engl J Med. 1986; 314:1643. [IDIS 217213] [PubMed 3713766]

126. American Academy of Pediatrics (AAP) Committee on Nutrition. Aluminum toxicity in infants and children. Pediatrics. 1996 (reaffirmed by AAP in Jan 2004); 97:413-6.

127. Milliner DS, Nebeker HG, Ott SM et al. Use of the deferoxamine infusion test in the diagnosis of aluminum-related osteodystrophy. Ann Intern Med. 1984; 101:775-80. [IDIS 194140] [PubMed 6208838]

128. Brittenham GM, Griffith PM, Nienhuis AW et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major, N Engl J Med. 1994; 331:567-73.

129. Olivieri NF, Nathan DG, MacMillan JH et al. Survival in medically treated patients with homozygous β-thalassemia. N Engl J Med. 1994; 331:574-8. [IDIS 334508] [PubMed 8047081]

130. Dover GJ, Valle D. Therapy for β-thalassemia—a paradigm for the treatment of genetic disorders. N Engl J Med. 1994; 331:609-10. [IDIS 334510] [PubMed 8047089]

131. Bronspiegel-Weintrob N, Olivieri NF, Tyler B et al. Effect of age at the start of iron chelation therapy on gonadal function in thalassemia major. N Engl J Med. 1990; 323:713-9. [IDIS 270513] [PubMed 2388669]

132. Grisaru D, Goldfarb AW, Gotsman MS et al. Deferoxamine improves left ventricular function in β-thalassemia. JAMA. 1986; 146:2344-9.

133. Porter JB. A risk-benefit assessment of iron-chelation therapy. Drug Saf. 1997; 17:407-21. [PubMed 9429839]

134. Gabutti V, Piga A. Results of long-term iron-chelating therapy. Acta Haematol. 1996; 95:26-36. [PubMed 8604584]

135. Modell B, Letsky EA, Flynn DM et al. Survival and desferrioxamine in thalassemia major. BMJ. 1982; 284:1081-4. [IDIS 149211] [PubMed 6802413]

136. Cazzola M, Locatelli F, De Stefano P. Deferoxamine in thalassemia major. N Engl J Med. 1995; 332:271-2. [IDIS 341337] [PubMed 7808503]

137. Klein GL. Aluminum in parenteral solutions revisited—again. Am J Clin Nutr. 1995; 61:449-56. [IDIS 344049] [PubMed 7872206]

138. American Society for Clinical Nutrition (ASCN)/American Society for Parenteral and Enteral Nutrition (ASPEN) Working Group on Standards for Aluminum Content of Parenteral Nutrition Solutions. Parenteral drug products containing aluminum as an ingredient or a contaminant: response to Food and Drug Administration notice of intent and request for information. J Parenteral Enteral Nutr. 1991; 15:194-8.

139. Food and Drug Administration. Parenteral drug products containing aluminum as an ingredient or a contaminant; notice of intent and request for information. 21 CFR Ch. 1. [Docket No. 90N-0056] Fed Regist. 1990; 55:20799-802. (IDIS 266263)

140. Pell GS, Shenkin A, Halls DJ. Aluminium contamination of intravenous pharmaceuticals, nutrients, and blood products. Lancet. 1986; 1:380.

141. American Academy of Pediatrics Committee on Nutrition. Pediatric nutrition handbook. 4th ed. Elk Grove Village, IL; 1998:261-2.

142. Voesct EE, Vreugdenhil G, Marx JJM. Iron-chelating agents in non-iron overload conditions. Ann Intern Med. 1994; 120:490-9. [IDIS 326408] [PubMed 8311372]

143. Tielemans C, Collart F, Wens J et al. Improvement of anaemia with deferoxamine in hemodialysis patients with aluminum-induced bone disease. Clin Nephrol. 1985; 24:237-41. [PubMed 4075595]

144. Altmann P, Plowman D, Marsh F et al. Aluminium chelation therapy in dialysis patients: evidence for inhibition of haemoglobin synthesis by low levels of aluminium. Lancet. 1988; 1:1012-5. [IDIS 241047] [PubMed 2896867]

145. Praga M, Enriquez de Salamanca R, Andres A et al. Treatment of haemodialysis-related porphyria cutanea tarda with deferoxamine. N Engl J Med. 1987; 316:547-8. [IDIS 225772] [PubMed 3808000]

146. Rosenlof K, Gronhagen-Riska C, Sovijari A et al. Beneficial effects of erythropoietin on haematological parameters, aerobic capacity, and body fluid composition in patients on haemodialysis. J Intern Med. 1989; 226:311-7. [PubMed 2809506]

147. Vreugdenhil G, Feelders RA, Coppens PJ et al. Possible mechanisms underlying potentiating effects of iron chelators in hematopoietic response to erythropoietin. Nephron. 1992; 61:475-6. [PubMed 1501748]

148. McCarthy JT, Kurtz SB, Mussman GV. Deferoxamine-enhanced fecal losses of aluminum and iron in a patient undergoing continuous ambulatory peritoneal dialysis. JAMA. 1987; 82:367-70.

149. Warady BA, Ford DM, Gaston CE et al. Aluminum intoxication in a child: treatment with intraperitoneal desferrioxamine. Pediatrics. 1986; 78:651-5. [IDIS 225124] [PubMed 3763276]

150. Klein GL, Snodgrass WR, Griffin MP et al. Hypocalcemia complicating deferoxamine therapy in an infant with parenteral nutrition-associated aluminum overload: evidence for a role of aluminum in the bone disease of infants. J Pediatr Gastroenterol Nutr. 1989; 9:400-3. [IDIS 260538] [PubMed 2515268]

151. Koo WWK, Kaplan LA, Bendon R et al. Response to aluminum in parenteral nutrition during infancy. J Pediatr. 1986; 109:877-83. [IDIS 227889] [PubMed 3095522]

152. Anon. Is aluminium a dementing ion? Lancet. 1992; 339:713-4. Editorial.

153. American Psychiatric Association. Practice guideline for the treatment of patients with Alzheimer’s disease and other dementias of late life. Am J Psychiatry. 1997; 154(Suppl):1-39.

154. Parnetti L, Senin U, Mecocci P. Cognitive enhancement therapy for Alzheimer’s disease: the way forward. Drugs. 1997; 53:752-68. [PubMed 9129864]

155. Crapper McLachlan DR, Dalton AJ, Kruck TPA et al. Intramuscular desferrioxamine in patients with Alzheimer’s disease. Lancet. 1991; 337:1304-8. [IDIS 281413] [PubMed 1674295]

156. Andrews DF, Crapper McLachlan DR, Dalton AJ et al. Desferrioxamine for Alzheimer’s disease. Lancet. 1991; 338:325-6.

158. Crapper McLachlan DR, Kruck TP, Lukiw WJ et al. Would decreased aluminium ingestion reduce the incidence of Alzheimer’s disease? Can Med Assoc J. 1991; 145:793-804.

159. Howland MA. Risks of parenteral deferoxamine for acute iron poisoning. J Toxicol Clin Toxicol. 1995; 34:491-7.

160. Bentur Y, McGuigan M, Koren G. Deferoxamine (desferrioxamine): new toxicities for an old drug. Drug Saf. 1991; 6:37-46. [PubMed 2029352]

161. De Virgiliis S, Congia M, Turco MP et al. Depletion of trace elements and acute ocular toxicity induced by desferrioxamine in patients with thalassaemia. Arch Dis Child. 1988; 63:250-5. [IDIS 240736] [PubMed 3355204]

162. Chiodo AA, Alberti PW, Sher GD et al. Desferrioxamine ototoxicity in an adult transfusion-dependent population. J Otolaryngol. 1997; 26:116-22. [PubMed 9106087]

163. Arden GB, Wonke B, Kennedy C et al. Ocular changes in patients undergoing long-term desferrioxamine treatment. Br J Ophthalmol. 1984; 68:873-7. [PubMed 6509007]

164. Porter JB, Jaswon MS, Huehns ER et al. Desferrioxamine ototoxicity: evaluation of risk factors in thalassaemic patients and guidelines for safe dosage. Br J Haematol. 1989; 73:403-9. [PubMed 2605127]

165. Tenenbein M, Kowalski S, Sienko A et al. Pulmonary toxic effects of continuous desferrioxamine administration in acute iron poisoning. Lancet. 1992; 339:699-701. [IDIS 293562] [PubMed 1347583]

166. Shannon M. Desferrioxamine in acute iron poisoning. Lancet. 1992; 339:1601. [IDIS 298299] [PubMed 1351565]

167. Macarol V, Yawalkar SJ. Desferrioxamine in acute iron poisoning. Lancet. 1992; 339:1601. [IDIS 298300] [PubMed 1351564]

168. Chan KW, Bond M, Fernandez W. Desferrioxamine in acute iron poisoning. Lancet. 1992; 339:1602.

169. Proudfoot AT, Simpson D, Dyson EH. Management of acute iron poisoning. Med Toxicol. 1986; 1:83-100. [IDIS 221647] [PubMed 3784842]

170. Anderson KJ, Rivers RPA. Desferrioxamine in acute iron poisoning. Lancet. 1992; 339:1602.

171. Helson L, Helson C, Braverman S et al. Desferrioxamine in acute iron poisoning. Lancet. 1992; 339:1603.

172. Castriota Scanderberg A, Izzi GC, Battufini A et al. Pulmonary syndrome and intravenous high-dose desferrioxamine. Lancet. 1990; 336:1511.

173. Freedman MH, Grisaru D, Olivieri N et al. Pulmonary syndrome in patients with thalessemia major receiving intravenous desferrioxamine infusions. 1990; 144:565-9.

174. Whitten CF, Gibson G, Good K et al. Studies in acute iron poisoning 11: desferrioxamine in the treatment of acute iron poisoning. Clinical observations, experimental studies, and theoretical considerations. Pediatrics. 1965; 36:322-5. [PubMed 5829325]

175. Whitten CF, Chen YC, Gibson GW. Studies in acute iron poisoning 11: desferrioxamine in the treatment of acute iron poisoning. Further observations of desferrioxamine in the treatment of acute experimental iron poisoning. Pediatrics. 1966; 38:102-10. [PubMed 5937669]

176. Weslin WE. Deferoxamine in the treatment of acute iron poisoning: clinical experiences with 172 children. Clin Pediatr Phila. 1966; 5:531-5. [PubMed 5911317]

177. Fischer DS, Parkman R, Fince SC. Acute iron poisoning in children. JAMA.

178. Low LC. Growth, puberty and endocrine function in beta-thalassaemia major. J Pediatr Endocrinol Metab. 1997; 10:175-84. [PubMed 9364350]

179. DeSanctis V, Pinamonti A, DiPalma A et al. Growth and development in thalassaemia major patients with severe bone lesions due to desferrioxamine. Eur J Pediatr. 1996; 155:368-72. [PubMed 8741032]

180. Saka N, Sukur M, Bundak R et al. Growth and puberty in thalassemia major. J Pediatr Endocrinol Metab. 1995; 8:181-6. [PubMed 8521192]

181. DeSanctis V, Katz M, Vullo C et al. Effect of different treatment regimes on linear growth and final height in beta-thalassemia major. Clin Endocrinol (Oxf). 1994; 40:791-8. [PubMed 8033371]

182. Hartkamp MJ, Babyn PS, Olivieri F. Spinal deformities in deferoxamine-treated homozygous beta-thalassemia major patients. Pediatr Radiol. 1993; 23:525-8. [PubMed 8309754]

183. Olivieri NF, Koren G, Harris J et al. Growth failure and bony changes induced by deferoxamine. Am J Pediatr Hematol Oncol. 1992; 14:48-56. [PubMed 1550263]

184. Orzincolo C, Scutellari PN, Castaldi G. Growth plate injury of the long bones in treated beta-thalassemia. Skeletal Radiol. 1992; 21:39-44. [PubMed 1546335]

185. Brill PW, Winchester P, Giardina PJ et al. Deferoxamine-induced bone dysplasia in patients with thalassemia major. Am J Roentgenol. 1991; 156:561-5.

186. Piga A, Luzzatto L, Capalbo P et al. High dose desferrioxamine as a cause of growth failure in thalassaemic patients. Eur J Haematol. 1988; 40:380-1. [PubMed 3366230]

187. Krishnan K, Trobe JD, Adams PT. Myasthenia gravis following iron chelation therapy with intravenous desferrioxamine. Eur J Haematol. 1995; 55:138-9. [PubMed 7628591]

188. Blake DR, Winyard P, Lunec J et al. Cerebral and ocular toxicity induced by desferrioxamine. Q J Med. 1985; 56:345-55. [IDIS 204455] [PubMed 4095247]

189. Brown SJ, Slizlfski WJ, Dadparvar S. Altered biodistribution of gallium-67 in a patient with aluminum toxicity treated with desferoxamine. J Nucl Med. 1990; 31:115-7. [IDIS 263578] [PubMed 2295931]

190. Nagamachi S, Hoshi H, Jinnouchi S et al. Gallium-67 scintigraphy in patients with hemochromatosis treated by deferoxamine. Ann Nucl Med. 1988; 2:35-9. [PubMed 3275103]

191. Baker DL, Manno CS. Rapid excretion of gallium-67 isotope in an iron-overloaded patient receiving high-dose intravenous deferoxamine. Am J Hematol. 1988; 29:230-2. [PubMed 3189321]

194. Roberts DJ, Rees D, Howard J et al. Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia. Cochrane Database of Systematic Reviews. 2005, Issue 4. Art. No.: CD004450. DOI:10.1002/14651858.CD004450.pub2.

195. Novartis, East Hanover, NJ: Personal communication.

196. Consensus conference summary. Diagnosis and treatment of aluminium overload in end-stage renal failure patients. Nephrol Dial Transplant. 1993; 8 (suppl 1):1-4.

197. Barata JD, D’Haese PC, Pires C et al. Low-dose (5 mg/kg) desferrioxamine treatment in acutely aluminium-intoxicated haemodialysis patients using two drug administration schedules. Nephrol Dial Transplant. 1996; 11:125-32. [PubMed 8649620]

198. Barton JC. Chelation therapy for iron overload. Curr Gastroenterol Rep. 2007; 9:74-82. [PubMed 17335681]

199. Cohen AR. New advances in iron chelation therapy. In: Berliner N, Linker C, Schiffer CA, eds. Hematology 2006. Washington, DC: American Society of Hematology; 2006:42-7.

200. National Kidney Foundation. Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for bone metabolism and disease in chronic kidney disease. 2003. Available at . Accessed 2008 Jan 9.

201. National Kidney Foundation. Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. 2005. Available at . Accessed 2008 Jan 29.

202. Perrone J. Iron. In: Goldfrank LR, Flomenbaum NE, Lewin NA et al, eds. Goldfrank’s toxicologic emergencies. 7th ed. New York: McGraw-Hill; 2002:548-57.

203. Howland MA. Deferoxamine. In: Goldfrank LR, Flomenbaum NE, Lewin NA et al, eds. Goldfrank’s toxicologic emergencies. 7th ed. New York: McGraw-Hill; 2002:558-62.

204. Liebelt EL, Kronfol R. Acute iron intoxication. From UpToDate website (). Updated 2007 Jan 8. Accessed 2008 Jan 10.

205. Anderson BD. Pediatric iron poisoning. From Medscape website: (). Medscape Pharmacists, 2000. Accessed 2008 Jan 10.

b. AHFS drug information 2009. McEvoy GK, ed. Deferoxamine mesylate. Bethesda, MD: American Society of Health-System Pharmacists; 2009.

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