Deferoxamine

Uses

Desferrioxamine Mesylate is used for Diagnosis of iron storage disease, Aluminum overload, Diagnosis of aluminum overload, Chronic iron overload, Acute iron poisoning

Deferoxamine is also used to associated treatment for these conditions: Aluminum overload, Chronic Iron Overload, Chronic aluminum overload, Iron Overload

How Deferoxamine works

Deferoxamine works in treating iron toxicity by binding trivalent (ferric) iron (for which it has a strong affinity), forming ferrioxamine, a stable complex which is eliminated via the kidneys. 100 mg of deferoxamine is capable of binding approximately 8.5 mg of trivalent (ferric) iron. Deferoxamine works in treating aluminum toxicity by binding to tissue-bound aluminum to form aluminoxamine, a stable, water-soluble complex. The formation of aluminoxamine increases blood concentrations of aluminum, resulting in an increased concentration gradient between the blood and dialysate, boosting the removal of aluminum during dialysis. 100 mg of deferoxamine is capable of binding approximately 4.1 mg of aluminum.

Dosage

Deferoxamine dosage

Intramuscular-

Diagnosis of iron storage disease:

• Adult: 500 mg as a single dose. To estimate the excretion of Fe in urine over the next 6 hr. An excretion of >1 g suggests Fe storage disease and >1.5 g suggests a pathological cause.

Intravenous-

Aluminum overload:

• Adult: Patients with end-stage renal failure, hemodialysis or hemofiltration patients: 5 mg/kg once a wk by slow infusion during the last hr of the dialysis session or 5 hr before the session in more severe cases. For patients on peritoneal dialysis: 5 mg/kg once a wk (via slow IV infusion/ SC/ IM/ intraperitoneally) should be given before the final exchange of the day.

Intravenous-

Diagnosis of aluminum overload:

• Adult: 5 mg/kg given via slow IV during the last hr of the dialysis session. Increase in serum aluminium conc above baseline >150 ng/ml (measured at the start of the next dialysis session) suggests aluminium overload.

Parenteral-

Chronic iron overload:

• Adult: Initially, 500 mg via IV/SC infusion (usually given over 8-12 hr or in some patients, 24 hr). Usual effective dose range: 20-60 mg/kg daily. Admin 3-7 times a wk depending on extent of iron overload. If given via IM inj, initial dose: 0.5-1 g daily as 1 or 2 injections; maintenance dose is determined by response.

Parenteral-

Acute iron poisoning:

• Adult: Initial dose: 15 mg/kg/hr by slow IV infusion, reducing after 4-6 hr so that the total dose dose not exceed 80 mg/kg in 24 hr. It can also be given via IM Inj as a single dose of 2 g.
• Child: Given via IM injection: 1 g as a single dose.

Intramuscular: Add 2 ml of sterile water for Inj to each 500 mg vial or 8 ml of sterile water for Inj to each 2 g vial.

Intravenous: Add 5 ml of sterile water for Inj to each 500 mg vial or 20 ml of sterile water for Inj to each 2 g vial. This results in a 10% solution. This can then be added to saline, glucose or Ringer's lactate solution to be used as an infusion.

Side Effects

Rapid IV injection: Flushing, urticaria, hypotension and shock. SC or IM injection: Local pain. Prolonged SC: Pruritus, erythema and swelling. GI disorders, dysuria, fever, allergic skin rashes, tachycardia, cardiac arrhythmias, convulsions and leg cramps; visual disturbances, cataract formation, hearing loss; may retard growth in very young childn. Pulmonary syndrome with high IV doses.

Toxicity

Intravenous LD₅₀ in mouse, rat, and rabbit is 340 mg/kg, 520 mg/kg, and 600 mg/kg, respectively. Subcutaneous LD₅₀ in mouse and rat is 1600 mg/kg and >1000 mg/kg, respectively. Oral LD₅₀ in mouse and rat is >3000 mg/kg and >1000 mg/kg, respectively. Nephrotoxicity, ototoxicity and retinal toxicity have been reported following long-term administration for chronic iron overload.

Precaution

Impaired renal function; may color the urine reddish-brown, exacerbate aluminum-related encephalopathy and precipitate seizure (prophylactic with antiepileptic if at risk); susceptible to infection; monitor urinary excretion of iron, ophthalmological, audiological and cardiac function examinations; pregnancy.

Interaction

Increased risk of neurological symptoms when used concurrently with phenothiazines. Ascorbic acid improves Fe excretion but it should not be given during the 1st mth of starting deferoxamine treatment as it may worsen Fe toxicity. May affect imaging results if given together with gallium-67.

Food Interaction

Deferoxamine Drug Interaction

Unknown: aspirin, aspirin, ciprofloxacin, ciprofloxacin, glucose, glucose, diltiazem, diltiazem, glycerin, glycerin, metoprolol, metoprolol, metoprolol, metoprolol, acetaminophen, acetaminophen, valproic acid, valproic acid, cholecalciferol, cholecalciferol

Deferoxamine Disease Interaction

Major: renal dysfunctionModerate: auditory dysfunction, hepatic impairment, ocular dysfunction, respiratory distress syndrome

Elimination Route

Deferoxamine is rapidly absorbed after intramuscular or subcutaneous administration, but only poorly absorbed from the gastrointestinal tract in the presence of intact mucosa.

Half Life

Biphasic elimination pattern in healthy volunteers with a first rapid phase half life of 1 hour and a second slow phase half-life of 6 hours.

Elimination Route

Deferoxamine mesylate is metabolized principally by plasma enzymes, but the pathways have not yet been defined. Some is also excreted in the feces via the bile.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Severe renal disease or anuria.

Acute Overdose

Symptoms: Hypotension, tachycardia, GI disturbances, transient loss of vision, aphasia, agitation, headache, nausea, pallor, CNS depression, coma, bradycardia and acute renal failure.

Management: There is no antidote and treatment is symptomatic. Haemodialysis is helpful in drug removal.

Storage Condition

Before reconstitution: store below 25°C.

After reconstitution: May store at room temperature for 7 days; protect from light. Do not refrigerate reconstituted solution.

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