What is the treatment regimen for iron overload using desferroxamine?

Deferoxamine Treatment for Iron Overload

For standard chronic iron overload, administer deferoxamine subcutaneously at 20-60 mg/kg/day over 8-12 hours, 5-7 days per week; for severe cardiac iron overload or acute heart failure, use continuous intravenous deferoxamine at 50-60 mg/kg/day for 24 hours daily. 1

Clinical Context and Indications

Deferoxamine is FDA-approved for acute iron intoxication and chronic iron overload from transfusion-dependent anemias, though it should not be used in primary hemochromatosis where phlebotomy is preferred 2. The drug is particularly critical in β-thalassemia major, where cardiac iron overload historically caused 70% of deaths before modern chelation protocols 3.

Standard Dosing Regimens

Chronic Iron Overload (Maintenance Therapy)

• Subcutaneous administration: 20-60 mg/kg/day via portable infusion pump over 8-12 hours (typically overnight), administered 5-7 days per week 1
• This route is preferred for long-term maintenance as it avoids infection risks associated with prolonged intravenous access 3
• Continuous subcutaneous infusion is approximately 80% as effective as intravenous therapy for iron chelation 4

Severe Cardiac Iron Overload or Heart Failure

• Continuous intravenous administration: 50-60 mg/kg/day for 24 hours daily 1
• This intensive regimen is reserved for patients with cardiac T2* <6 ms or decompensated heart failure 3
• Clinical stabilization may occur within 14 days but can take months 3
• After the acute period, conversion from 24-hour intravenous to 24-hour subcutaneous infusion can be considered 3

Combination Therapy

• Deferoxamine plus deferiprone: Daily subcutaneous deferoxamine (at standard doses) combined with oral deferiprone 75 mg/kg/day in 3 divided doses 3
• This combination is used extensively for patients with impaired left ventricular function without decompensated heart failure 3
• Combination therapy shows superior reduction in serum ferritin and improved left ventricular ejection fraction compared to monotherapy 5
• Both drugs are taken together every day (not alternating) 3

Administration Technique

• Subcutaneous route: Use a portable infusion pump with slow infusion over 8-12 hours 1, 4
• Intravenous route: Requires careful management of the intravenous line, anticoagulation, and scrupulous sterile access techniques 3
• Local adverse reactions at infusion sites (pain, swelling) are common and should be monitored 5

Monitoring Protocol

Baseline and Regular Assessments

• Serum ferritin: Every 3 months (monthly if possible), with target <1000 ng/mL 1, 6
• Cardiac T2 MRI:* Annually in transfusion-dependent patients to assess cardiac iron content 1, 6
• Liver iron concentration: Annually using MRI techniques 1
• Cardiac function: LVEF assessment (can improve substantially within weeks), electrocardiography, and echocardiography annually starting at age 10 3, 1

Treatment Adjustment Based on Cardiac T2*

• T2 <6 ms:* Treat as acute heart failure with maximal chelation (47% risk of heart failure within 1 year) 3, 6
• T2 6-10 ms:* Intensified but not necessarily maximal chelation therapy 3
• T2 10-20 ms:* Conservative management with dose modifications or alternative chelators 3
• T2 >20 ms:* Standard maintenance dosing 3

Treatment Duration and Long-Term Management

• Lifelong chelation is typically required in transfusion-dependent patients 1, 6
• After resolution of decompensated heart failure, treatment must continue for several years to completely remove cardiac iron 3, 6
• Cardiac iron removal is extremely slow even with intensive chelation 3
• Compliance with chelation is essential for long-term survival, requiring specialist center follow-up 3

Special Populations

Pediatric Patients

• Iron chelation should not be given to children under age 3 with minimal iron overload unless significant iron mobilization (≥1 mg iron/day) can be demonstrated 2
• In children with sickle cell disease on chronic transfusion programs, initiate chelation after 12-20 transfusions 6
• Start chelation when serum ferritin reaches ≥1000 ng/mL or after ≥20 red blood cell transfusions 6

Renal Impairment

• Patients with renal failure may require early dialysis to remove the iron chelator, though efficacy is not proven 3
• Deferasirox should be avoided in acute heart failure or marginal renal perfusion 3, 6

Critical Pitfalls to Avoid

• Do not use aggressive inotropic therapy in thalassemia patients with heart failure, as it can be detrimental 3
• Do not stop intensive chelation prematurely after cardiac function improves, as cardiac iron clearance lags behind functional improvement and relapse risk is high 3
• Do not adjust chelation based solely on blood pressure in thalassemia patients, as they typically have low baseline blood pressure 3
• Monitor for chelator-mediated toxicity by adjusting treatment according to liver iron and serum ferritin levels 3

Adverse Events and Safety

• Deferoxamine has fewer adverse events than deferiprone, with significantly lower rates in comparative trials 5
• Common local reactions include pain and swelling at infusion sites 5
• Long-term intravenous access carries infection risk, making subcutaneous administration preferable when feasible 3
• Deferiprone causes more permanent treatment withdrawals due to adverse events (agranulocytosis, neutropenia, arthropathy, gastrointestinal symptoms) compared to deferoxamine 5, 7