NAME OF DRUG
deferoxamine mesylate

CLASSIFICATION

Iron chelating agent

ALTERNATE NAME

DESFERAL

INDICATIONS

• to facilitate removal of iron in acute iron intoxication and chronic iron overload
• treatment of aluminum toxicity in chronic renal failure

RECONSTITUTION AND STABILITY

• store at room temperature

• IM use: reconstitute deferoxamine mesylate 500mg vial with 2 mL sterile water for injection to provide a solution of 210 mg/mL

•  IV use: reconstitute 500mg vial with 5 mL sterile water for injection to make a 10% solution (~100 mg/mL); withdraw entire contents from vial

• reconstituted solutions should not be stored longer than 24 hours at room temperature

COMPATIBILITY

• compatible with NS, D5W, RL
• incompatible with other drugs

ROUTES OF ADMINISTRATION

• Acute iron intoxication
      IM - not recommended due to inferior efficacy, pain at injection site and erratic absorption
      IV infusion - infusion rate not to exceed 15 mg/kg/hr
  
• Chronic iron overload and aluminum toxicity
      IM - used in addition to I.V. infusions with each unit of blood transfused
      IV, S.C. infusion - further dilution with NS, D5W or RL is required
      Intraperitoneally in peritoneal dialysis patients
  
  VH & HSC ADMINISTRATION POLICY

A - Not to be administered by the direct IV route
H - IV/SC infusion rates must be controlled with an automated infusion control device


DOSAGE

ACUTE IRON INTOXICATION (Adults):

IM (patients not in shock)

• initial dose 90 mg/kg, not exceeding a total dose of 2 g, then 45 mg/kg every 4-12 hours if necessary

IV (preferred route)

• 15mg/kg/hour via continuous infusion (rates up to 35 mg/kg/hr have been tolerated by severely poisoned adults)
• Total daily dose: the manufacturer recommends a maximum daily dose of 6 g; however higher doses are often required and up to 16 g/day and higher have been tolerated
• Consider discontinuation of therapy when all of the following occur: symptoms of systemic iron poisoning iron poisoning have resolved; radiopacities no longer present on abdominal radiograph; serum iron level < 63 umol/L; and vin rose urine colouration, if initially present, has cleared

CHRONIC IRON OVERLOAD (Adults ):

IM

• 0.5-1g for 6-7 days/week in addition: 2g IV to be administered with, but separate from, each unit of blood transfused

IV, SC

• 20-60mg/kg (1-4g) infused over 8-12 hours (infusion rate should not exceed 15 mg/kg/hr)
• Dosages up to 200 mg/kg/day have been used in thalassemia major

ALUMINUM TOXICITY

Hemodialysis: 5mg/kg in 150mLD5W infused IV over last hour of dialysis
Intraperitoneal: 5mg/kg added to final daily dialysate exchange

POTENTIAL HAZARDS OF PARENTERAL ADMINISTRATION

• pain and induration at injection site
• following too rapid IV injection - hypotension, flushing, generalized erythema, tachycardia and shock
• local inflammation and irritation following subcutaneous injection if a concentration greater than 500mg/2mL is used

IMPORTANT IMPLICATIONS

• theoretically, 100 mg of deferoxamine binds 8.5 mg of iron and 4.1mg aluminum
• serum iron (SI) and total iron binding capacity (TIBC) should be regularly monitored; in the acute setting, treatment is indicated if SI>TIBC, SI>63 umol/L and a TIBC is unavailable or if SI is not readily available and the patient is symptomatic
• leukocytosis (WBC > 15000 x A9/L), hyperglycemia (blood glucose >8.5) or diarrhea strongly suggest SI will be in the toxic range
• I.V. and S.C. routes have been reported to be more effective than the I.M. route
• other adverse reactions include: ocular and auditory toxicities, abdominal discomfort, diarrhea, leg cramps, thrombocytopenia and increased risk of opportunistic infections
• deferoxamine complexes with iron to form ferrioxamine; this chelate is excreted through the kidneys and imparts a reddish color to the urine
• long term therapy for chronic iron storage diseases may increase the risk of allergic type reactions (pruritus, rash, anaphylaxis)
• may cause a slight increase in sodium and calcium excretion
• contraindicated in patients with severe renal failure or anuria not on dialysis

Rev. Dec 2005