Deferoxamine

Dosage Forms & Strengths

powder for injection

• 500mg/vial
• 2g/vial

Acute Iron Poisoning

IM administration is indicated for all patients NOT in shock; administer 1g IM initially and then 500mg Q4hr for 2 doses

Depending upon clinical response, subsequent doses of 500mg Q4-12hr can be administered

Maximum dose: 6g in 24 hours

IV administration should be reserved for patients in a state of cardiovascular collapse or shock; 1g slow IV infusion

Rate of infusion should not exceed 15mg/kg/hr for the first dose; subsequent doses should not be infused at a faster rate than 125mg/hr  

Chronic Iron Overload

SC administration: 1-2g (20-40mg/kg/day) SC over 8-24 hours using a small portable pump capable of providing continuous mini-infusion; individualize infusion duration

IV administration in patients with IV access: 40-50mg/kg/day over 8-12 hours for 5-7 days/ week (maximum of < 60mg/kg/day and an IV infusion rate of <15mg/kg/hr)

IM administration: 0.5-1g QD (maximum of 1g QD)  

Additional Information

Can be administered prior to or following same day blood transfusion in patients that are poorly compliant; should not be administered concurrently as this can lead to errors in interpretation of ADRs

Dosage Forms & Strengths

powder for injection

• 500mg/vial
• 2g/vial

Acute Iron Poisoning

<3 years: Safety and effectiveness has not been established

≥3 years: Administer 1g IM initially and then 500mg Q4hr for 2 doses for all patients not in shock

Depending upon clinical response, subsequent doses of 500mg Q4-12hr can be administered; maximum dose: 6g in 24 hours

IV administration should be reserved for patients in a state of cardiovascular collapse or shock; 1g slow IV infusion

Rate of infusion should not exceed 15mg/kg/hr for the first dose; subsequent doses should not be infused at a faster rate than 125mg/hr

20 mg/kg IM (for all patients not in shock) or IV (only if patient in cardiovascular collapse/shock); then, 10 mg/kg IM/IV q4hr x2; then, depending on clinical circumstance, may administer addtional doses of 10 mg/kg IM/IV q4-12hr PRN 

IV infusion rate: Initial 1 g at 15 mg/kg/hr, all subsequent doses no more than 125 mg/hr

No more than 6 g/day (IM/IV), but in severe cases should continue infusion up to 24 hours

Chronic Iron Overload

<3 years: Safety and effectiveness has not been established

≥3 years: 0.5-1g IM QD (maximum of 1g QD)

SC administration: 1-2g (20-40mg/kg/day) SC over 8-24 hours using a small portable pump capable of providing continuous mini-infusion; individualize infusion duration  

IV administration in patients with IV access: 40-50mg/kg/day over 8-12 hours for 5-7 days/ week (maximum of < 60mg/kg/day and an IV infusion rate of <15mg/kg/hr)  

Additional Information

Can be administered prior to or following same day blood transfusion in patients that are poorly compliant; should not be administered concurrently as this can lead to errors in interpretation of ADRs

Frequency Not Defined

Injection site reactions (eg, localized irritation, induration, infiltration, pain, erythema, wheal formation, eschar, burning, swelling, pruritus, crust, vesicles, local edema); these may be associated with systemic allergic reactions

Systemic reactions (eg, abdominal pain, arthralgia, asthma, fever, headache, myalgia, nausea, vomiting)

Cardiovascular reactions (eg, hypotension with too rapid IV infusion, tachycardia, shock)

Hypersensitivity reactions (eg, anaphylactic reaction with or without shock, angioedema, generalized rash, urticaria)

Digestive reactions (eg, abdominal discomfort, diarrhea, nausea, vomiting)

Hematologic reactions (eg, blood dyscrasia including thrombocytopenia and leucopenia)

Hepatic reactions (eg, increased transaminases, hepatic dysfunction)

Musculoskeletal reactions (eg, muscle spasms, growth retardation and bone changes including metaphyseal dysplasia are common in doses ≥ 60 mg/kg, especially those who begin iron chelation in the first three years of life; reduced risk if doses are kept to ≤ 40 mg/kg)

Nervous System reactions (eg, neurological disturbances including dizziness, peripheral sensory, motor, or mixed neuropathy, paresthesias, seizures; exacerbation or precipitation of aluminum-related dialysis encephalopathy)

Special Senses reactions (eg, high-frequency sensorineural hearing loss and/or tinnitus are uncommon if dosage guidelines are not exceeded and if dose is reduced when ferritin levels decline; visual disturbances inlcuding decreased acuity, blurred vision, loss of vision, dyschromatopsia, night blindness, visual field defects, scotoma, retinopathy (pigmentary degeneration), optic neuritis, and cataracts are rare if dosage guidelines are not exceeded)

Respiratory reactions (eg, acute respiratory distress syndrome with dyspnea, cyanosis, and/or interstitial infiltrates)

Very rare generalized rash

Urogenital reactions including dysuria, acute renal failure, increased serum creatinine and renal tubular disorders

Postmarketing Reports

Renal dysfunction, including renal failure; monitor patients for changes in renal function (eg, increased serum creatinine)

Desferal chelates iron by forming a stable complex that prevents the iron from entering into further chemical reactions. It readily chelates iron from ferritin and hemosiderin but not readily from transferrin; it does not combine with the iron from cytochromes and hemoglobin. Desferal does not cause any demonstrable increase in the excretion of electrolytes or trace metals. Theoretically, 100 parts by weight of Desferal is capable of binding approximately 8.5 parts by weight of ferric iron.

Desferal 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.

Serious side effects have been reported with deferoxamine. See the "Drug Precautions" section.

Common side effects of deferoxamine include the following:

• injection site pain
• rash
• fever
• headache
• dizziness
• stomach pain
• diarrhea
• nausea
• vomiting

This is not a complete list of deferoxamine side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

You should not use this medication if you are allergic to deferoxamine, if you have severe kidney disease, or if you are unable to urinate.

To make sure you can safely use deferoxamine, tell your doctor if you have any of these other conditions:

• kidney disease (or if you are on dialysis);

• heart disease;

• liver disease;

• vision or hearing problems;

• asthma or other breathing disorder;

• low levels of calcium in your blood (hypocalcemia); or

• a parathyroid disorder.

If you need to have any type of x-ray or CT scan using a dye that is injected into a vein, you may need to temporarily stop using deferoxamine. Be sure the doctor knows ahead of time that you are using this medication.

FDA pregnancy category C. It is not known whether deferoxamine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether deferoxamine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Long-term use of deferoxamine can slow a child's growth. Tell your doctor if the child using this medication is not growing or gaining weight properly.

Usual Adult Dose for Iron Poisoning -- Acute:

Initial dose: 1000 mg, IM or IV (maximum IV rate: 15 mg/kg/hour)
Maintenance dose: 500 mg, IM or IV, every 4 hours, for 2 doses; additional 500 mg doses every 4 to 12 hours may be given based on clinical response
Maximum dose: 6000 mg per 24 hour period

Comments:
-IM administration is preferred for all patients not in shock.
-Slow IV administration should only be used for cardiovascular collapse.
-As soon as the clinical condition allows, discontinue IV and switch to IM administration.
-This drug is an adjunct to, not a substitute for, standard treatment for acute iron intoxication (e.g. inducing emesis, gastric lavage)

Use: Acute iron poisoning

Usual Adult Dose for Iron Poisoning -- Chronic:

1000 to 2000 mg, subcutaneously over 8 to 24 hours, daily
or
40 to 50 mg/kg/day, IV over 8 to 12 hours (maximum IV rate: 15 mg/kg/hour), 5 to 7 days per week
Maximum IV dose: 60 mg/kg/day
or
500 to 1000 mg, IM,
Maximum IM dose: 1000 mg/day

Comments:
-Subcutaneous administration is recommended.
-Intravenous administration can be used in patients with intravenous access.

Use: Chronic iron overload

Usual Pediatric Dose for Iron Poisoning -- Acute:

3 years and older:
Initial dose: 1000 mg, IM or IV (maximum IV rate: 15 mg/kg/hour)
Maintenance dose: 500 mg, IM or IV, every 4 hours, for 2 doses; additional 500 mg doses every 4 to 12 hours may be given based on clinical response
Maximum dose: 6000 mg per 24 hour period

Comments:
-IM administration is preferred for all patients not in shock.
-Slow IV administration should only be used for cardiovascular collapse.
-As soon as the clinical condition allows, discontinue IV and switch to IM administration.
-This drug is an adjunct to, not a substitute for, standard treatment for acute iron intoxication (e.g. inducing emesis, gastric lavage)

Use: Acute iron poisoning

Usual Pediatric Dose for Iron Poisoning -- Chronic:

3 years and older:
1000 to 2000 mg, subcutaneously over 8 to 24 hours, daily
or
20 to 40 mg/kg/day, IV over 8 to 12 hours (maximum IV rate: 15 mg/kg/hour), 5 to 7 days per week
Maximum IV dose: 40 mg/kg/day (until growth has ceased)
or
500 to 1000 mg, IM,
Maximum IM dose: 1000 mg/day

Comments:
-Monitor for body weight and growth every 3 months.
-Subcutaneous administration is recommended.
-Intravenous administration can be used in patients with intravenous access.

Use: Chronic iron overload

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a muscle or as an infusion into a vein over a period of time.
• It is given as an infusion under the skin over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

Acute Toxicity

Intravenous LD50s (mg/kg): mice, 287; rats, 329.

Signs and Symptoms

Inadvertent administration of an overdose or inadvertent intravenous bolus administration/rapid intravenous infusion may be associated with hypotension, tachycardia and gastrointestinal disturbances; acute but transient loss of vision, aphasia, agitation, headache, nausea, pallor, CNS depression including coma, bradycardia and acute renal failure have been reported.

Acute respiratory distress syndrome has been reported following treatment with excessively high intravenous doses of Deferoxamine mesylate in patients with acute iron intoxication and in patients with thalassemia.

Treatment

There is no specific antidote.  Deferoxamine mesylate should be discontinued and appropriate symptomatic measures undertaken.

Deferoxamine mesylate is readily dialyzable.

• Deferoxamine Mesylate
• Desferrioxamine
• Desferrioxamine Methanesulphonate
• DFM

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Frequency not defined.

Cardiovascular: Flushing, hypotension, shock, tachycardia

Central nervous system: Brain disease (aluminum toxicity/dialysis-related), dizziness, headache, neuropathy (peripheral, sensory, motor, or mixed), paresthesia, seizure

Dermatologic: Skin rash, urticaria

Endocrine & metabolic: Growth suppression (children), hyperparathyroidism (aggravated), hypocalcemia

Gastrointestinal: Abdominal distress, abdominal pain, diarrhea, nausea, vomiting

Genitourinary: Dysuria, urine discoloration (reddish color)

Hematologic & oncologic: Dysplasia (metaphyseal; children <3 years; dose related), leukopenia, thrombocytopenia

Hepatic: Hepatic insufficiency, increased serum transaminases

Hypersensitivity: Anaphylaxis (with or without shock), angioedema, hypersensitivity

Infection: Infection (Yersinia, mucormycosis)

Local: Injection site reaction (burning, crust, edema, erythema, eschar, induration, infiltration, irritation, pain, pruritus, swelling, vesicles, wheal formation)

Neuromuscular & skeletal: Arthralgia, muscle spasm, myalgia

Ophthalmic: Blurred vision, cataract, chromatopsia, corneal opacity, decreased peripheral vision, decreased visual acuity, nocturnal amblyopia, optic neuritis, retinal pigment changes, scotoma, vision loss, visual field defect

Otic: Hearing loss, tinnitus

Renal: Acute renal failure, increased serum creatinine, renal tubular disease

Respiratory: Acute respiratory distress (dyspnea, cyanosis, and/or interstitial infiltrates), asthma

Miscellaneous: Fever

Adverse events have been observed in animal reproduction studies. Toxic amounts of iron or deferoxamine have not been noted to cross the placenta; however, the metabolic effects of a maternal overdose may adversely affect the fetus. In case of acute iron toxicity, treatment during pregnancy should not be withheld (Chang 2011).

Applies to deferoxamine: injection powder for solution

Along with its needed effects, deferoxamine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking deferoxamine:

• Bluish fingernails, lips, or skin
• blurred vision or other problems with vision
• convulsions (seizures)
• difficulty with breathing or fast breathing
• fast heartbeat
• hearing problems
• redness or flushing of the skin

• Diarrhea
• difficult urination
• fever
• leg cramps
• nausea
• stomach and muscle cramps
• stomach discomfort
• unusual bleeding or bruising
• vomiting

• Agitation
• coma
• confusion
• cough
• decreased urine output
• depression
• difficulty with swallowing
• dizziness
• headache
• hives
• hostility
• irritability
• itching
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• lethargy
• muscle twitching
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain
• shortness of breath
• skin rash
• stupor
• swelling of the face, ankles, or hands
• tightness in the chest
• unusual tiredness or weakness
• wheezing

Some side effects of deferoxamine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site

Animal studies showed delayed ossification and skeletal anomalies. There are no controlled data in human pregnancy. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus. AU TGA pregnancy category: B3 US FDA pregnancy category: C