Deferoxamine

Usage

Deferoxamine is prescribed for treating acute iron intoxication and chronic iron overload resulting from transfusion-dependent anemias (e.g., thalassemia, sickle cell disease). Its pharmacological classification is as an iron chelator. It works by binding free iron in the body, forming a stable complex (ferrioxamine) that can be excreted in the urine and feces, thus reducing excess iron levels.

Alternate Names

Deferoxamine is also known as desferrioxamine. A common brand name is Desferal.

How It Works

Pharmacodynamics: Deferoxamine specifically binds to ferric iron (Fe3+), forming ferrioxamine, a water-soluble complex. This complex is then eliminated from the body, primarily through the kidneys (glomerular filtration and renal tubular secretion), and a small portion is also excreted in the bile and feces. Deferoxamine does not chelate iron that is essential for hemoglobin or other iron-containing proteins.

Pharmacokinetics: Deferoxamine is poorly absorbed when administered orally and is, therefore, given parenterally. Subcutaneous (SC) infusion is the preferred route for chronic iron overload. Intramuscular (IM) administration is used for acute iron poisoning in stable patients, and intravenous (IV) administration is reserved for cases of cardiovascular collapse due to iron intoxication. The drug is metabolized to ferrioxamine and smaller inactive metabolites.

Mechanism of Action: Deferoxamine acts as a chelating agent by binding free iron in tissues and fluids, preventing iron-catalyzed free radical damage. It has a high affinity for ferric iron. This interaction does not involve receptor binding, enzyme inhibition, or neurotransmitter modulation in the traditional sense. The ferrioxamine complex is stable and inactive, ready for excretion. Elimination occurs primarily through renal excretion and partially by hepatic excretion/biliary elimination.

Dosage

Standard Dosage

Adults:

• Chronic Iron Overload: 40-50 mg/kg/day SC infused over 8-12 hours, 5-7 days/week. The maximum dose should not exceed 60 mg/kg/day.
• Acute Iron Poisoning (IM): Initial dose of 1 g IM, followed by 500 mg every 4 hours for two doses. Subsequent doses of 500 mg may be given every 4-12 hours as needed, with a maximum total dose of 6 g in 24 hours.
• Acute Iron Poisoning (IV - for cardiovascular collapse): Initial dose of 1 g IV infused at a rate not exceeding 15 mg/kg/hour. Subsequent doses of 500 mg can be administered every 4-12 hours, with a maximum infusion rate of 125 mg/hour and a maximum daily dose of 6 g in 24 hours.

Children:

• Chronic Iron Overload: 20-40 mg/kg/day SC infused over 8-12 hours, 5-7 days/week. The maximum dose should not exceed 40 mg/kg/day until growth has ceased.
• Acute Iron Poisoning: Dosage must be determined by the physician based on the child’s weight and clinical condition.

Special Cases:

• Elderly Patients: Start with a lower dose and adjust cautiously based on renal function and concomitant conditions.
• Patients with Renal Impairment: Use with caution. Adjust the dose downwards. Contraindicated in severe renal disease or anuria.
• Patients with Hepatic Dysfunction: Adjust the dose cautiously. Close monitoring is recommended.
• Patients with Comorbid Conditions: Careful dose adjustment and monitoring are needed. In patients with heart failure, avoid concurrent use with Vitamin C.

Clinical Use Cases

The use of deferoxamine is not indicated for intubation, standard surgical procedures, mechanical ventilation, or general ICU use. Its primary clinical applications are for acute iron poisoning and chronic iron overload, with IV administration specifically for patients in cardiovascular collapse due to iron toxicity. There are no dosage recommendations for specific clinical settings like general intubation, mechanical ventilation, or ICU use. Emergency situations are addressed in the context of acute iron poisoning.

Dosage Adjustments

Dose adjustments are based on renal/hepatic function, patient response, and serum ferritin levels. Close monitoring of serum ferritin and iron levels is necessary during therapy.

Side Effects

Common Side Effects:

Injection site reactions (pain, redness, swelling), abdominal discomfort, diarrhea, nausea, vomiting, headache, fever, rash.

Rare but Serious Side Effects:

Allergic reactions (anaphylaxis), hypotension, hearing loss, vision changes (blurred vision, cataracts, night blindness, optic neuritis, loss of color vision), growth retardation in children, infection, pulmonary toxicity (acute respiratory distress syndrome), neurologic effects (peripheral neuropathy, seizures), renal impairment.

Long-Term Effects:

Hearing impairment, visual disturbances, bone changes.

Adverse Drug Reactions (ADR):

Anaphylaxis, severe hypotension, acute respiratory distress syndrome, acute renal failure, seizures.

Contraindications

• Hypersensitivity to deferoxamine.
• Severe renal disease or anuria.

Drug Interactions

• Prochlorperazine: Concomitant use can lead to temporary loss of consciousness.
• Vitamin C: May worsen iron toxicity in heart failure patients, especially in the early stages of treatment. Use cautiously after the first month of deferoxamine therapy.
• Gallium-67: Can interfere with imaging studies using Gallium-67.
• Other iron preparations (especially oral): Reduced absorption of oral iron.

Pregnancy and Breastfeeding

• Pregnancy: Deferoxamine is Pregnancy Category C. Animal studies have shown potential adverse fetal effects. Use only if potential benefit outweighs risk to the fetus.
• Breastfeeding: Limited data suggest that deferoxamine might be excreted in breast milk. It is generally recommended to avoid breastfeeding during deferoxamine therapy. Infant’s iron levels should be monitored if breastfeeding is continued.

Drug Profile Summary

• Mechanism of Action: Iron chelator, binding free iron for urinary and fecal excretion.
• Side Effects: Injection site pain, GI upset, hearing/vision changes, allergic reactions (anaphylaxis).
• Contraindications: Hypersensitivity, severe renal disease/anuria.
• Drug Interactions: Prochlorperazine, vitamin C (in heart failure patients), gallium-67.
• Pregnancy & Breastfeeding: Category C; not recommended during breastfeeding.
• Dosage: Variable based on indication, route, and patient characteristics.
• Monitoring Parameters: Serum ferritin, iron levels, renal and hepatic function, audiometry, ophthalmologic exams.

Popular Combinations

Vitamin C (after initial deferoxamine therapy), given to enhance iron chelation in some cases.

Precautions

• General Precautions: Renal and hepatic function monitoring, audiometric and ophthalmologic evaluations, monitoring for infection.
• Specific Populations:
  • Pregnant Women: Potential risk to fetus.
  • Breastfeeding Mothers: Avoid if possible; monitor infant iron if breastfeeding continued.
  • Children & Elderly: Dose adjustments may be necessary.
• Lifestyle Considerations: No specific lifestyle considerations are indicated apart from general health maintenance.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Deferoxamine?

A: The dosage varies by indication, route, and patient characteristics. For chronic iron overload, the standard dose is 40-50 mg/kg/day SC for adults and 20-40 mg/kg/day SC for children, infused over 8-12 hours, 5-7 days/week. For acute iron poisoning, the initial IM dose is 1g, followed by 500 mg every 4 hours for two doses for adults. IV administration is reserved for cardiovascular collapse due to iron poisoning. Pediatric and special population doses should be individualized by a physician.

Q2: What is the mechanism of action of Deferoxamine?

A: Deferoxamine chelates free iron, forming ferrioxamine, which is then excreted, primarily through the kidneys.

Q3: What are the major side effects of Deferoxamine?

A: Injection site reactions, gastrointestinal disturbances, hearing loss, visual disturbances, and allergic reactions, including anaphylaxis.

Q4: Can Deferoxamine be used during pregnancy?

A: It is a Pregnancy Category C drug. Use only if the potential benefit outweighs risk to the fetus.

Q5: Is it safe to breastfeed while taking Deferoxamine?

A: Limited data suggest that deferoxamine might be excreted in breast milk. It is generally recommended to avoid breastfeeding or monitor the infant’s iron levels if breastfeeding continues.

Q6: How is Deferoxamine administered?

A: It is administered parenterally via SC infusion (preferred for chronic overload), IM injection (acute poisoning in stable patients), or IV infusion (cardiovascular collapse due to iron poisoning). Oral administration is ineffective due to poor absorption.

Q7: What are the contraindications for Deferoxamine?

A: Hypersensitivity to deferoxamine and severe renal disease or anuria.

Q8: What are the key drug interactions with Deferoxamine?

A: Prochlorperazine, vitamin C (especially in heart failure patients), and gallium-67.

Q9: What monitoring is required during Deferoxamine therapy?

A: Serum ferritin and iron levels, renal and hepatic function, hearing tests (audiometry), and eye exams (ophthalmologic evaluations) should be monitored regularly.

Q10: What is the role of Vitamin C in conjunction with Deferoxamine therapy?

A: Vitamin C can enhance iron chelation but should be used cautiously and generally only after an initial month of deferoxamine therapy, especially in patients with heart failure, as it might worsen iron toxicity early in the treatment.