Desferal

Antidotes, Systemic
Chelating Agents

Administer intravenously or subcutaneously. Although the manufacturer indicates that intramuscular injection is the preferred route unless the patient is in shock, available literature supports using continuous intravenous infusion for any patient with acute iron toxicity. Furthermore, it appears that subcutaneous infusion over 8 to 12 hours is the preferred route of administration in most patients with chronic iron overload.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if visibly opaque particles, discoloration or foreign particles are observed. The reconstituted deferoxamine solution is an isotonic, clear and colorless to slightly-yellowish solution.
Deferoxamine reconstituted with Sterile Water for Injection is for single use only. Discard any unused portion.

Reconstitution
Reconstitute each 500-mg vial with 5 mL of Sterile Water for Injection for a resultant concentration of 95 mg/mL.
Storage: If not used immediately, store at room temperature between 20 and 25 degrees C (68 to 77 degrees F) for a maximum period of 24 hours. Do not refrigerate reconstituted solution.
 
Dilution
Dilute the reconstituted IV solution in 150 mL of 5% Dextrose for injection, 0.45% Sodium Chloride for injection, 0.9% Sodium Chloride for injection, or Lactated Ringer's Injection for a final concentration of 3 to 3.5 mg/mL.
Storage: If not used immediately, store at room temperature between 20 and 25 degrees C (68 to 77 degrees F) for a maximum period of 24 hours.
 
Continuous Intravenous Infusion
Infuse IV generally at a maximum rate of 15 mg/kg/hour; however, higher infusion rates up to 35 mg/kg/hour have been safely used. Rapid infusion may cause hypotension, erythema, urticaria, wheezing, convulsions, tachycardia, or shock.
If the patient is also receiving blood, deferoxamine should be administered in a line that is separate from the blood.

Reconstitution
Reconstitute each 500-mg vial with 2 mL of Sterile Water for Injection for a resultant concentration of 213 mg/mL.
Storage: If not used immediately, store at room temperature between 20 and 25 degrees C (68 to 77 degrees F) for a maximum period of 24 hours. Do not refrigerate reconstituted solution.
 
Intramuscular Injection
Inject deeply into a large muscle mass.

Reconstitution
Reconstitute each 500-mg vial with 5 mL of Sterile Water for Injection for a resultant concentration of 95 mg/mL.
Storage: If not used immediately, store at room temperature between 20 and 25 degrees C (68 to 77 degrees F) for a maximum period of 24 hours. Do not refrigerate reconstituted solution.
 
Continuous Subcutaneous Infusion
Infuse over 8 to 12 hours using a portable, light-weight infusion pump; longer infusion times up to 24 hours may be used.
Deferoxamine is not formulated to support subcutaneous bolus injection.

corneal opacification / Delayed / Incidence not known
optic neuritis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
night blindness / Delayed / Incidence not known
retinopathy / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
ototoxicity / Delayed / Incidence not known
seizures / Delayed / Incidence not known
dementia / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
cyanosis / Early / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known

blurred vision / Early / Incidence not known
scotomata / Delayed / Incidence not known
cataracts / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
encephalopathy / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known
erythema / Early / Incidence not known
hypotension / Rapid / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
growth inhibition / Delayed / Incidence not known
dyspnea / Early / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
dysuria / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known

tinnitus / Delayed / Incidence not known
infection / Delayed / Incidence not known
fever / Early / Incidence not known
dizziness / Early / Incidence not known
paresthesias / Delayed / Incidence not known
headache / Early / Incidence not known
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
flushing / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
abdominal pain / Early / Incidence not known
diarrhea / Early / Incidence not known
vomiting / Early / Incidence not known
nausea / Early / Incidence not known
myalgia / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known

Desferal

Rx

Iron-chelating agent
Used in the treatment of acute iron intoxication and transfusional iron overload in patients with chronic anemia
Also chelates aluminum and may be used for aluminum overload in patients with chronic kidney disease on dialysis

15 mg/kg/hour continuous IV infusion until signs and symptoms of iron poisoning are resolved and serum iron concentration within normal range. Higher doses (up to 35 mg/kg/hour) have been safely used and may be needed in severe ingestions. Although the FDA-approved labeling recommends a maximum dosage of 6 g/24 hours, higher doses are often used (16 to 20 g/day) and may be clinically necessary.    In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.

15 mg/kg/hour continuous IV infusion until signs and symptoms of iron poisoning are resolved and serum iron concentration within normal range. Higher doses (up to 35 mg/kg/hour) have been safely used and may be needed in severe ingestions. Although the FDA-approved labeling recommends a maximum dosage of 6 g/24 hours, higher doses are often used (16 to 20 g/day) and may be clinically necessary. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.

15 mg/kg/hour continuous IV infusion until signs and symptoms of iron poisoning are resolved and serum iron concentration within normal range. Higher doses (up to 35 mg/kg/hour) have been safely used and may be needed in severe ingestions. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.

NOTE: Although intramuscular administration is FDA-approved, this route is not preferred and is typically not used in clinical practice.

1 g IM once, followed by 500 mg IM every 4 to 12 hours as needed based on clinical response. Although the FDA-approved labeling recommends a maximum dosage of 6 g/24 hours, higher doses are often used (16 to 20 g/day) and may be clinically necessary. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.

40 to 90 mg/kg/dose (Max: 2 g/dose) IM every 4 to 8 hours as needed based on clinical response. The FDA-approved dosage is 1 g IM once, followed by 500 mg IM every 4 to 12 hours as needed based on clinical response. Although the FDA-approved labeling recommends a maximum dosage of 6 g/24 hours, higher doses are often used (16 to 20 g/day) and may be clinically necessary. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.

40 to 90 mg/kg/dose IM every 4 to 8 hours as needed based on clinical response. In general, deferoxamine can be discontinued within 24 hours; however, up to 48 hours of therapy may necessary.

20 to 60 mg/kg/day subcutaneously over 8 to 24 hours for 5 to 7 days/week. General deferoxamine requirements by serum ferritin concentration are 25 mg/kg/day for serum ferritin below 2,000 ng/mL, 35 mg/kg/day for serum ferritin 2,000 to 3,000 ng/mL, and up to 55 mg/kg/day for serum ferritin more than 3,000 ng/mL. Do not regularly exceed an average daily dose of 50 mg/kg/day except when very intensive chelation is needed in persons who have completed growth. If ferritin concentrations decrease below 1,000 ng/mL, the risk of deferoxamine toxicity increases; consider lowering the total weekly dose in these cases.

20 to 60 mg/kg/day subcutaneously over 8 to 24 hours for 5 to 7 days/week. General deferoxamine requirements by serum ferritin concentration are 25 mg/kg/day for serum ferritin below 2,000 ng/mL, 35 mg/kg/day for serum ferritin 2,000 to 3,000 ng/mL, and up to 55 mg/kg/day for serum ferritin more than 3,000 ng/mL. Do not regularly exceed an average daily dose of 50 mg/kg/day except when very intensive chelation is needed in persons who have completed growth. If ferritin concentrations decrease below 1,000 ng/mL, the risk of deferoxamine toxicity increases; consider lowering the total weekly dose in these cases.

25 to 35 mg/kg/dose subcutaneously over 8 to 24 hours for 5 to 7 days/week. Safe and effective use has not been established; however, some children with thalassemia younger than 3 years will exhibit signs of iron toxicity. Evaluate hepatic iron concentration in children that have required regular transfusions for at least 1 year; if elevated, deferoxamine therapy may be beneficial. Start at the lower end of the dosing range and increase the dose only if hepatic iron concentration or total body iron burden are still elevated.

40 to 50 mg/kg/day IV over 8 to 12 hours for 5 to 7 days/week. Max: 60 mg/kg/day.

20 to 40 mg/kg/day IV over 8 to 12 hours for 5 to 7 days/week. Max: 40 mg/kg/day until growth (body weight and linear growth) has stopped.

25 to 35 mg/kg/dose IV over 8 to 12 hours for 5 to 7 days/week. Safe and effective use has not been established; however, some children with thalassemia younger than 3 years will exhibit signs of iron toxicity. Evaluate hepatic iron concentration in children that have required regular transfusions for at least 1 year; if elevated, deferoxamine therapy may be beneficial. Start at the lower end of the dosing range and increase the dose only if hepatic iron concentration or total body iron burden are still elevated.

NOTE: Although intramuscular administration is FDA-approved, this route is not preferred and is typically not used in clinical practice.

0.5 to 1 g IM once daily.

0.5 to 1 g IM once daily.

5 mg/kg/dose by slow IV infusion over the last hour of dialysis session. Measure serum aluminum before deferoxamine infusion and 2 days later before the next dialysis session. The test is considered positive if the serum aluminum rise is at least 50 mcg/L.

5 mg/kg/dose by slow IV infusion over the last hour of dialysis session. Measure serum aluminum before deferoxamine infusion and 2 days later before the next dialysis session. The test is considered positive if the serum aluminum rise is at least 50 mcg/L.

5 mg/kg/dose by slow IV infusion over the last hour of dialysis once weekly for 2 months. Then discontinue deferoxamine for one month and perform the deferoxamine-stimulation test again.

5 mg/kg/dose by slow IV infusion over the last hour of dialysis once weekly for 2 months. Then discontinue deferoxamine for one month and perform the deferoxamine-stimulation test again.

NOTE: The intraperitoneal route is preferred in patients receiving continuous peritoneal dialysis.

5 mg/kg/dose intraperitoneally once weekly prior to the final exchange of the day once weekly for 2 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.

5 mg/kg/dose intraperitoneally once weekly prior to the final exchange of the day once weekly for 2 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.

5 mg/kg/dose by slow IV infusion over 1 hour once weekly 5 hours before dialysis for 4 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.

5 mg/kg/dose by slow IV infusion over 1 hour once weekly 5 hours before dialysis for 4 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.

NOTE: The intraperitoneal route is preferred in patients receiving continuous peritoneal dialysis.

5 mg/kg/dose intraperitoneally once weekly prior to the final exchange of the day for 4 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.

5 mg/kg/dose intraperitoneally once weekly prior to the final exchange of the day for 4 months. Then discontinue deferoxamine for 1 month and perform the deferoxamine-stimulation test again.

†Indicates off-label use

Specific guidelines are not available; for patients with hepatic impairment, dose selection should usually start at the low end of the dosing range.

Deferoxamine is contraindicated in patients with severe renal impairment or anuria or with other severe renal disease, since the drug and iron chelate (i.e., ferrioxamine) are eliminated primarily by the kidney. For patients with mild or moderate renal impairment, dose selection should usually start at the low end of the dosing range.
 
Intermittent hemodialysis
Both deferoxamine and ferrioxamine are removed by hemodialysis.

Ascorbic Acid, Vitamin C: (Major) Patients should be advised not to take ascorbic acid, vitamin C supplements along with deferoxamine chelation therapy unless such supplements are prescribed with the approval of their health care professional. Patients with iron overload usually become vitamin C deficient, probably because iron oxidizes the vitamin. Vitamin C can be a beneficial adjunct in iron chelation therapy because it facilitates iron chelation and iron complex excretion. As an adjuvant to iron chelation therapy (e.g., deferoxamine), vitamin C (in doses up to 200 mg/day for adults, 50 mg/day in children < 10 years of age or 100 mg/day in older children) may be given in divided doses, starting after an initial month of regular treatment with deferoxamine. However, higher doses of ascorbic acid, vitamin C can facilitate iron deposition, particularly in the heart tissue, causing cardiac decompensation. In patients with severe chronic iron overload, the concomitant use of deferoxamine with > 500 mg/day PO of vitamin C in adults has lead to impairment of cardiac function; the dysfunction was reversible when vitamin C was discontinued. The manufacturer of deferoxamine recommends certain precautions for the coadministration of vitamin C with deferoxamine. First, vitamin C supplements should not be given concurrently with deferoxamine in patients with heart failure. Secondly, in other patients, such supplementation should not be started until 1 month of regular treatment with deferoxamine, and should be given only to patients receiving regular deferoxamine treatments. Do not exceed vitamin C doses of 200 mg/day for adults, 50 mg/day in children < 10 years of age, or 100 mg/day in older children, given in divided doses. Clinically monitor all patients, especially the elderly, for signs or symptoms of decreased cardiac function.
Cyclosporine: (Moderate) Although not specifically studied, reduced serum concentrations of deferoxamine may occur in patients taking other CYP3A4 substrates such as cyclosporine. If these drugs are used together, monitor patients for a decrease in the effects of cyclosporine. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including cyclosporine, may increase the risk of acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and cyclosporine concomitantly.
Prochlorperazine: (Moderate) Concurrent treatment with deferoxamine and prochlorperazine may lead to a temporary impairment of consciousness. The mechanism of the interaction is not clear.
Vigabatrin: (Major) Vigabatrin should not be used with deferoxamine, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.

Deferoxamine/Deferoxamine Mesylate/Desferal Intramuscular Inj Pwd F/Sol: 2g, 500mg
Deferoxamine/Deferoxamine Mesylate/Desferal Intravenous Inj Pwd F/Sol: 2g, 500mg
Deferoxamine/Deferoxamine Mesylate/Desferal Subcutaneous Inj Pwd F/Sol: 2g, 500mg

Generally, 15 mg/kg/hour continuous IV infusion for acute iron toxicity; however, higher doses (up to 35 mg/kg/hour) have been safely used; FDA-approved maximum is 6 g/day; however, higher doses (16 to 20 g/day) are often needed. 60 mg/kg/day subcutaneously/IV/IM for chronic iron overload.

Generally, 15 mg/kg/hour continuous IV infusion for acute iron toxicity; however, higher doses (up to 35 mg/kg/hour) have been safely used; FDA-approved maximum is 6 g/day; however, higher doses (16 to 20 g/day) are often needed. 60 mg/kg/day subcutaneously/IV/IM for chronic iron overload.

Generally, 15 mg/kg/hour continuous IV infusion for acute iron toxicity; however, higher doses (up to 35 mg/kg/hour) have been safely used; FDA-approved maximum is 6 g/day; however, higher doses (16 to 20 g/day) are often needed. 50 mg/kg/day subcutaneously/IV/IM for chronic iron overload.

3 to 12 years: Generally, 15 mg/kg/hour continuous IV infusion for acute iron toxicity; however, higher doses (up to 35 mg/kg/hour) have been safely used; FDA-approved maximum is 6 g/day; however, higher doses (16 to 20 g/day) are often needed. 50 mg/kg/day subcutaneously/IV/IM for chronic iron overload.
1 to 2 years: Safety and efficacy have not been established; however, doses up to 15 to 35 mg/kg/hour continuous IV infusion for acute iron toxicity and 35 mg/kg/day IV/subcutaneously for chronic iron overload have been used off-label.

Safety and efficacy have not been established; however, doses up to 15 to 35 mg/kg/hour continuous IV infusion for acute iron toxicity and 35 mg/kg/day IV/subcutaneously for chronic iron overload have been used off-label.

Ferric ions bind to the 3 hydroxamic groups of deferoxamine, creating ferrioxamine, a stable, water-soluble complex that is then readily excreted by the kidneys. Deferoxamine's affinity for iron is greater than that of other chelating agents, and administration of the drug does not appear to increase the excretion of electrolytes or other trace minerals. Deferoxamine readily chelates iron from ferritin and hemosiderin but not readily from transferrin; it does not combine with the iron from cytochromes and hemoglobin.
One gram of deferoxamine has the potential to chelate with 85 mg of iron, but the rate of iron excreted is dependent on pH, occurring most readily at an acidic pH. Deferoxamine complexes preferentially, if not exclusively, with the ferric ion. Concomitant administration of ascorbic acid with deferoxamine may increase the excretion of iron by promoting the conversion of ferrous ions to ferric ions. While enhancement of the renal elimination of iron is believed to be the predominant action of deferoxamine, some believe that deferoxamine may exert protective actions at the cellular level. The chelation of deferoxamine (and its subsequent conversion to ferrioxamine) may limit iron entry into cells because ferrioxamine is less permeable than deferoxamine. It is also possible that deferoxamine chelates intracellular extramitochondrial iron.
Aluminum excretion by the kidneys is also increased by deferoxamine. One gram of deferoxamine has the potential to bind 41 mg of aluminum.

Deferoxamine is administered intravenously, subcutaneously, and rarely, intramuscularly. The Vd of deferoxamine ranges from 0.6 to 1.33 L/kg. Ferrioxamine is formed when deferoxamine binds the ferric cation. This binding transforms deferoxamine from a straight chain structure to a stable octahedral compound with distinctly different pharmacokinetic characteristics. The volume of distribution of ferrioxamine (0.2 L/kg) is much smaller than deferoxamine suggesting that the molecule remains exclusively in the extracellular fluid. Deferoxamine 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. The elimination half-life of deferoxamine is approximately 20 to 30 minutes.

There are no available data on deferoxamine use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. However, based on animal data, deferoxamine can cause malformations at doses less than the human dose. In animal reproduction studies, subcutaneous administration of deferoxamine to pregnant animals (mice or rabbits) during organogenesis at doses approximately 0.2 or greater (mice) and 0.7 or greater (rabbits) times the maximum recommended human dose resulted in maternal toxicity and adverse developmental outcomes. Advise pregnant women of the potential risk to a fetus. Consider the benefits and risks of deferoxamine for the mother and possible risks to the fetus when prescribing deferoxamine during pregnancy.

There are no data on the presence of deferoxamine or its metabolite in either human or animal milk, the effects on the breastfed child, or the effects on milk production. It is not known whether deferoxamine is excreted in human milk. Because of the potential for serious adverse reactions in the breastfed child, advise patients to avoid breast-feeding during treatment with deferoxamine, and for one week after the last dose.