DESCRIPTION

Deferoxamine mesylate (Desferal) is an antidote for iron poisoning.

FORMS AND USES

• Each vial contains 500 mg of lyophilized powder.
• Deferoxamine is used therapeutically for:
  • Acute iron poisoning.
  • Chronic iron overload from multiple transfusions.
  • Chronic aluminum overload from treatment with dialysis or total parenteral nutrition.

MECHANISM OF ACTION

• Free iron in the ferric (Fe⁺³) form causes iron toxicity by directly injuring the intestinal mucosa and creating oxygen free radicals.
• Deferoxamine chelates ferric iron, to form ferrioxamine, a less toxic compound than ferric iron.
• Deferoxamine does not remove iron from transferrin, ferritin, hemoglobin, hemosiderin, or cytochrome enzymes.
• Ferrioxamine is not metabolized and is excreted unchanged in the urine.
• One mole of deferoxamine binds 1 mole of iron; therefore, 100 mg of deferoxamine binds 9.35 mg of iron.

DRUG AND DISEASE INTERACTIONS

Concurrent administration of deferoxamine with ascorbic acid is not recommended for treating either acute or chronic iron overload because it may mobilize iron, which both enhances excretion and allows further tissue deposition.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category C. Studies have shown that the drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
• Deferoxamine crosses the placenta poorly; however, its use is recommended in acute maternal iron poisoning to optimize the mother's condition.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

• Treatment of acute iron toxicity
  • Signs of iron toxicity, including protracted vomiting or diarrhea, persistent tachycardia, hypotension, altered mental status, increased anion gap metabolic acidosis, acidemia, or hematochezia
  • Serum iron greater than 500 µg/dl on blood drawn 4 to 6 hours after ingestion
• Chronic iron overload from multiple transfusions
• Chronic aluminum overload states in patients on chronic dialysis

CONTRAINDICATIONS

• Renal insufficiency or oliguric renal failure are relative contraindications
• Ferrioxamine complex is renally eliminated; therefore, combined deferoxamine and hemodialysis treatment may be useful in the treatment of iron poisoning.

ADVERSE EFFECTS

Hypotension

• Dose-related hypotension occurs commonly with rapid intravenous infusion or following the intramuscular administration of a large dose.
• Hypotension is avoided by using continuous intravenous infusion instead of bolus intramuscular administration.
• If hypotension due to deferoxamine occurs, the rate of infusion should be decreased.

Anaphylactoid Reactions

• The risk of reaction is increased with large dose or rapid infusion rate.
• Anaphylactoid reactions increase the risk of hypotension in patients who are already volume depleted.

Infections

• Yersinia enterocolitica infection. Yersinia enterocolitica is a siderophore and thrives in a high iron environment as provided by the iron-deferoxamine complex.
• Fungal infection (mucormycosis, Rhizopus, phycomycosis) is associated rarely with treatment of iron or aluminum toxicity.

Ocular Toxicity

• Decreased visual acuity, decreased visual fields, impairment of night vision, altered color vision, retrobulbar optic neuropathy, and cataracts have been reported.
• The risk increases with larger doses and long-term therapy for chronic iron overload.

Auditory Toxicity

• Tinnitus and sensorineural hearing loss have been reported.
• There is an increased risk with larger doses and chronic therapy for states of chronic iron overload.

Adult Respiratory Distress Syndrome

• Pulmonary edema has been reported after prolonged use (more than 24 hours) of deferoxamine treatment of acute iron overdose.
• Deferoxamine can usually be tapered or discontinued within 24 hours.

Renal Insufficiency

Renal insufficiency may be related to hypotension produced by severe iron toxicity.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS
  • Hypotension
  • Anaphylactoid Reactions
  • Infections
  • Ocular Toxicity
  • Auditory Toxicity
  • Adult Respiratory Distress Syndrome
  • Renal Insufficiency

ACUTE IRON TOXICITY

Intravenous Dose

• The initial adult or pediatric dose is 15 mg/kg/hour by continuous infusion. This dose is adequate for most patients.
• The dose should be titrated to signs of iron toxicity, the serum iron concentration, and severity of acidosis. Rates of 20 to 25 mg/kg/h are usually adequate to treat severe poisoning, although rates as high as 40 mg/kg/h have been used when treating life-threatening iron toxicity.
• As the patient improves, the hourly dose of deferoxamine can be tapered.
• Although the package labeling indicates that 6 g is the recommended maximum 24-hour dose, this limit is based on intramuscular administration. Much larger doses are often needed. Intravenous doses of more than 25 gfday are commonly administered without adverse effect.
• Only severe cases of iron toxicity require more than 24 hours of continuous infusion.

Intramuscular Dose

Intramuscular treatment is not usually recommended for the treatment of acute iron toxicity due to erratic absorption and the increased incidence of adverse events. Pain and induration at the injection site may occur if an intramuscular route of administration is used. It has been used to begin therapy in some cases where intravenous access is difficult. However, intravenous administration is needed for crystalloid resuscitation, and this approach is discouraged.

• The initial adult dose is 1 g followed by 500 mg every 4 to 12 hours.
• The initial pediatric dose is 50 mg/kg followed by 50 mg/kg every 4 to 6 hours.

CHRONIC IRON OVERLOAD

Intravenous Dose

• Concurrent with blood transfusions or dialysis. Doses of 15 mg/kg/h to a dose of 2 g have been administered with each unit of blood or during each dialysis session.
• Deferoxamine should not be administered in the same intravenous line as blood.
• Intramuscular dose. The adult or pediatric dose is 500 mg to 1 g per day.
• Subcutaneous infusion has been reported useful.
• Rectal administration is not recommended due to decreased excretion of iron compared with intravenous administration.

Section Outline:

• ACUTE IRON TOXICITY
  • Intravenous Dose
  • Intramuscular Dose
• CHRONIC IRON OVERLOAD
  • Intravenous Dose

• Following deferoxamine administration, the serum iron level becomes uninterpretable.
• A deferoxamine challenge test is not recommended.
• Absence of a vin rosec discoloration of the urine following the administration of deferoxamine does not exclude iron toxicity.
• In the treatment of acute iron toxicity deferoxamine should be administered by the intravenous route, not intramuscularly.
• The health-care provider should not delay deferoxamine while awaiting iron levels in severely symptomatic patients.
• Hemodialysis may be useful in patients with renal insufficiency or renal failure and iron toxicity to remove the ferrioxamine complex, which is normally renally excreted.
• Oral administration is contraindicated because it may increase the absorption of iron.
• The total iron-binding capacity (TIBC) measured at a time of concurrent deferoxamine administration may be falsely elevated (the TIBC is not clinically useful when managing acute iron toxicity).

Toxic effect of other metals: other specified metals.

See Also: SECTION IV, Aluminum and Iron chapters.

RECOMMENDED READING

Goldfrank LR. Iron. In: Goldfrank LR, et al., eds. Goldfrank's toxicologic emergencies, 6th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Edwin K. Kuffner

Reviewer: Katherine M. Hurlbut