Deferoxamine Mesylate

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

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

Contraindications

• Severe renal disease or anuria118 b (although may be used for diagnosis119 127 195 196 200 201 or treatment of aluminum toxicity in patients with chronic renal failure undergoing dialysis† [see Renal Impairment under Cautions]).104 105 106 107 108 109 126 195 196 197 200 201

Warnings/Precautions

Warnings

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

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

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

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

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

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.)

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

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

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

Category C.118 b

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

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

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

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

Storage

Parenteral

≤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

• 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

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.