Deferoxamine is a medication primarily used to treat iron overload caused by blood transfusions in conditions such as thalassemia and hemochromatosis. It belongs to a class of drugs known as iron chelators, which means it binds to excess iron in the bloodstream and helps remove it from the body.

Iron overload can occur in individuals who require frequent blood transfusions, as each transfusion adds additional iron to the body. Over time, this excess iron can accumulate in organs such as the heart, liver, and pancreas, leading to serious complications such as organ damage and failure.

Deferoxamine works by binding to the excess iron and forming a compound that can be excreted from the body through urine and feces. It is typically administered through intravenous infusion or subcutaneous injection.

Desferal (Deferoxamine) is an iron-chelating drug that is used in the treatment of acute and chronic iron overload as in patients with thalassemia. It also binds aluminum and is used in patients on hemodialysis with aluminum toxicity.

Indications of Desferal (Deferoxamine):

• Acute iron toxicity:
  • It is used as an adjunct in the treatment of acute iron intoxication.
• Chronic iron overload:
  • It is indicated for the treatment of chronic iron overload secondary to multiple transfusions (often due to the presence of thalassemia major or sickle cell disease).
• Off Label Use of Deferoxamine in Adults:
  • Diagnosis or treatment of aluminum-induced toxicity associated with chronic kidney disease (CKD).

Desferal (Deferoxamine) dose in adults:

Desferal (Deferoxamine) dose in the treatment of Acute iron toxicity:

In the treatment of acute iron toxicity, the recommended dose of deferoxamine varies based on the severity of toxicity and the route of administration. Here's a typical dosing regimen:

Intravenous (IV) Route:

• Initial dose: 1,000 mg
• Followed by 500 mg every 4 hours for 2 doses
• Subsequent doses of 500 mg may be administered every 4 to 12 hours based on clinical response
• Maximum recommended dose: 6,000 mg per day (as per manufacturer's recommendation)

It's important to note that the IV route is preferred, especially in cases of severe toxicity characterized by cardiovascular collapse, systemic symptoms (such as coma, shock, metabolic acidosis, or gastrointestinal bleeding), or peak serum iron levels exceeding 500 mcg/dL. IV administration allows for rapid and effective delivery of deferoxamine, particularly in critical situations.

Intramuscular (IM) Route:

• IM administration may be used according to the manufacturer's recommendations but is not preferred and rarely indicated.

The use of deferoxamine in situations where the peak serum iron concentration is less than 500 mcg/dL or when severe toxicity is not evident is a subject of clinical debate. Individual patient factors, including the severity of symptoms and the risk of iron toxicity, should be carefully considered when determining the appropriate dosing regimen.

Desferal (Deferoxamine) dose in the treatment of Chronic iron overload:

In the treatment of chronic iron overload, the dosage of deferoxamine can vary depending on the route of administration and individual patient factors. Here are the typical dosing regimens:

Intramuscular (IM) Route:

• Initial dose: 500 to 1,000 mg per day
• Maximum dose: 1,000 mg per day

Intravenous (IV) Route:

• Initial dose: 40 to 50 mg/kg per day
• Maximum dose: 60 mg/kg per day
• Administration duration: Over 8 to 12 hours
• Frequency: 5 to 7 days per week

Subcutaneous (SubQ) Route:

• Initial dose: 1,000 to 2,000 mg per day or 20 to 40 mg/kg per day
• Administration duration: Over 8 to 24 hours

Off-label dosing:

• IV or SubQ: 25 to 50 mg/kg over 8 to 10 hours
• Frequency: 5 to 7 days per week

It's important to note that individual patient factors, including the severity of iron overload and tolerance to the medication, should be considered when determining the appropriate dosage. Close monitoring by healthcare professionals is essential to ensure the safe and effective management of chronic iron overload.

Desferal (Deferoxamine) Dose in the Diagnosis of aluminum-induced toxicity with CKD (off-label use:

In the diagnosis of aluminum-induced toxicity with chronic kidney disease (CKD), particularly in off-label use scenarios, the following deferoxamine dosing regimen may be employed:

Intravenous (IV) Route:

• Test dose: 5 mg/kg during the last hour of dialysis
• Indications for testing:
  • Baseline serum aluminum concentrations are 60 to 200 mcg/L
  • Clinical signs/symptoms of toxicity
  • Aluminum exposure prior to parathyroid surgery
• Measure aluminum just prior to deferoxamine administration
• Remeasure aluminum 2 days later
• Test is considered positive if serum aluminum increases by ≥50 mcg/L
• Do not use if unstimulated aluminum serum concentrations are >200 mcg/L to avoid deferoxamine-induced neurotoxicity.

This dosing regimen aims to assess the response of serum aluminum levels to deferoxamine administration, particularly in patients with CKD who may be at risk of aluminum toxicity due to factors such as dialysis treatment or aluminum exposure from medications or other sources. It's crucial to follow guidelines and recommendations closely to ensure the safe and effective use of deferoxamine in diagnosing aluminum-induced toxicity in CKD patients.

Desferal (Deferoxamine) dose in the treatment of aluminum toxicity with CKD (off-label use):

In the treatment of aluminum toxicity with chronic kidney disease (CKD), particularly in off-label use scenarios, the following deferoxamine dosing regimen may be employed:

Intravenous (IV) Route:

• Administer after diagnostic deferoxamine test dose.
• Note: Do not perform the deferoxamine-stimulation test and administer intensive dialysis until serum aluminum concentrations are <200 mcg/L to avoid the risk of deferoxamine-associated neurotoxicity.

If serum aluminum concentration rises to ≥300 mcg/L two days after the deferoxamine test dose or there are side effects after the deferoxamine-stimulation test:

• Dosage: 5 mg/kg once a week, administered 5 hours before dialysis for 4 months.
• After 4 months: Discontinue deferoxamine for one month and perform the deferoxamine-stimulation test again.

If serum aluminum concentration is <300 mcg/L two days after the deferoxamine test dose and there are no side effects after the deferoxamine-stimulation test:

• Dosage: 5 mg/kg once a week, administered during the last hour of dialysis for 2 months.
• After 2 months: Discontinue deferoxamine for one month and perform the deferoxamine-stimulation test again.

This dosing regimen aims to manage aluminum toxicity in CKD patients while minimizing the risk of deferoxamine-associated neurotoxicity. It involves careful monitoring of serum aluminum concentrations and adjustment of deferoxamine dosage based on the patient's response and tolerance. Close adherence to guidelines and recommendations is essential for the safe and effective treatment of aluminum toxicity in CKD patients.

Desferal Desferal (Deferoxamine) dose in children:

Desferal (Deferoxamine) dose for Acute iron intoxication:

In the treatment of acute iron intoxication, the dosage of deferoxamine varies based on the severity of toxicity and the route of administration. Here are the typical dosing regimens:

Children & Adolescents

Intravenous (IV) Route:

• Continuous IV infusion:
  • Initial dose: 15 mg/kg/hour
  • Maximum daily dose: 80 mg/kg/day, not to exceed 6 g/day
• Initial bolus dose:
  • Initial dose: 20 mg/kg (maximum dose: 1,000 mg) administered no faster than 15 mg/kg/hour
  • Followed by 10 mg/kg (maximum dose: 500 mg) over 4-hour intervals for 2 doses
  • Subsequent doses of 10 mg/kg (maximum dose: 500 mg) over 4 to 12 hours may be repeated depending on clinical response
  • Maximum daily dose: 6 g/day
• IV dosing may also be used if symptoms are not severe

Intramuscular (IM) Route:

• Initial dose: 90 mg/kg/dose for one dose
• Subsequent doses: 45 mg/kg/dose every 4 to 12 hours as needed
• Maximum single dose:
  • Children: 1,000 mg
  • Adults: 2,000 mg
• Maximum daily dose: 6 g/day

It's important to note that individual patient factors, including the severity of symptoms and the risk of iron toxicity, should be considered when determining the appropriate dosage. Close monitoring by healthcare professionals is essential to ensure the safe and effective management of acute iron intoxication.

Desferal (Deferoxamine) dose in Chronic iron overload:

In the treatment of chronic iron overload, the dosage of deferoxamine can vary depending on the route of administration and the age of the patient. Here are the typical dosing regimens:

Intravenous (IV) Route:

• Children and growing adolescents: 20 to 40 mg/kg/day over 8 to 12 hours, 5 to 7 days per week
  • Usual maximum daily dose: 40 mg/kg/day
• Adolescents once growth has ceased: 40 to 50 mg/kg/day over 8 to 12 hours, 5 to 7 days per week
  • Usual maximum daily dose: 60 mg/kg/day

Subcutaneous (SubQ) Route via a portable, controlled infusion device:

• 20 to 40 mg/kg/day over 8 to 12 hours, 3 to 7 days per week
• Maximum daily dose: 2,000 mg/day
• Doses exceeding 60 mg/kg/day have not been shown to provide additional benefit

It's essential to adhere to the recommended dosing guidelines provided by the manufacturer and consider factors such as patient age, growth status, and response to treatment when determining the appropriate dosage of deferoxamine for chronic iron overload. Close monitoring by healthcare professionals is necessary to ensure the safe and effective management of iron overload in pediatric and adolescent patients.

Desferal (Deferoxamine) dose for chronic iron overload in patients with Sickle cell disease:

In the treatment of chronic iron overload in sickle cell disease, particularly in children and adolescents, the typical dosing regimen for deferoxamine is as follows:

Subcutaneous (SubQ) Route:

• Dosage: 25 mg/kg/day
• Administration duration: Over 8 hours
• Dose and duration may be increased as needed based on individual patient response and tolerance

It's essential to closely monitor patients receiving deferoxamine therapy for chronic iron overload, adjusting the dosage and duration as necessary to effectively manage iron levels while minimizing the risk of adverse effects.

Desferal (Deferoxamine) dose in chronic iron overload in patients with Thalassemia:

In the treatment of chronic iron overload in thalassemia, the dosage of deferoxamine varies depending on the age of the patient and their growth status. Here are the typical dosing regimens:

Children and Growing Adolescents:

• Subcutaneous (SubQ) infusion:
  • Dosage: 20 to 40 mg/kg/day over 8 to 12 hours
  • Frequency: 6 to 7 nights per week
  • Maximum daily dose: 40 mg/kg/day

Adolescents once growth has ceased:

• SubQ infusion (preferred):
  • Dosage: 40 to 60 mg/kg/day over 8 to 12 hours
  • Frequency: 6 to 7 nights per week
  • Maximum daily dose: 2,000 mg/day
• SubQ bolus:
  • Dosage: 45 mg/kg/dose
  • Frequency: 5 times per week

It's important to monitor ferritin levels regularly and adjust the deferoxamine dosage as needed to maintain the therapeutic index below 0.025. Additionally, individual patient factors and response to treatment should be considered when determining the appropriate dosage for managing chronic iron overload in thalassemia.

Desferal (Deferoxamine) dose in the treatment of aluminum-induced bone disease in chronic renal failure:

In the treatment of aluminum-induced bone disease in chronic renal failure, particularly in children and adolescents, the dosage of deferoxamine is as follows:

Test (Diagnostic) Dose:

• Intravenous (IV) route: 5 mg/kg as a single dose infused over the last hour of dialysis.
• Serum aluminum concentration should be measured 2 days later.
• Depending on the change in serum aluminum concentration, treatment with deferoxamine may be indicated.

Treatment:

• Monitor serum aluminum levels closely.
• Refer to National Kidney Foundation guidelines for additional details on treatment algorithms.

It's important to note that deferoxamine treatment should only be initiated if serum aluminum concentration is within the intended range of 60 to 200 mcg/L. If serum aluminum concentration exceeds 200 mcg/L, intensive dialysis should be employed until serum aluminum levels decrease below the threshold for chelation therapy.

In the treatment of aluminum serum concentration rise to ≥300 mcg/L or if adverse effects occur with the test dose, the recommended deferoxamine dosage is as follows:

Intravenous (IV) Route:

• Dosage: 5 mg/kg once a week
• Timing: Administered 5 hours before dialysis
• Duration: Treatment should continue for 4 months

For aluminum serum concentration rise to <300 mcg/L, the recommended deferoxamine dosage is:

Intravenous (IV) Route:

• Dosage: 5 mg/kg once a week
• Timing: Administered during the last hour of dialysis
• Duration: Treatment should continue for 2 months

These dosing regimens aim to manage elevated aluminum levels effectively while minimizing the risk of adverse effects associated with deferoxamine therapy. It's crucial to closely monitor serum aluminum concentrations during treatment and adjust the dosage or duration as needed based on the patient's response.

Pregnancy Risk Factor C

• While studies on animals have shown some problems during pregnancy with deferoxamine, it's not clear if it can harm the baby directly.
• However, if a pregnant woman takes too much deferoxamine or iron, it might affect her body in a way that could harm the baby.
• If a pregnant woman has a sudden overdose of iron, she should still get treatment, even though there's a small risk to the baby.

Deferoxamine use during breastfeeding:

• It's uncertain if deferoxamine passes into breast milk.
• One woman who took deferoxamine while breastfeeding had normal levels of iron in her breast milk, and her twins didn't have any reported problems.
• However, caution is still advised when giving deferoxamine to breastfeeding women, according to the manufacturer's recommendation.

Desferal (Deferoxamine) Dose adjustment in renal disease:

For individuals with severe kidney disease or anuria (lack of urine production), the use of deferoxamine is not recommended according to the manufacturer's labeling in the United States.

However, some clinicians have made adjustments based on the patient's kidney function:

• For adults with creatinine clearance (CrCl) greater than 50 mL/minute, no adjustment to the dose of deferoxamine is typically needed.
• For adults with CrCl between 10 to 50 mL/minute or those undergoing continuous renal replacement therapy (CRRT), the dose of deferoxamine may be reduced to 25% to 50% of the normal dose.
• For adults with CrCl less than 10 mL/minute or those undergoing hemodialysis or peritoneal dialysis, the use of deferoxamine should be avoided.

These adjustments aim to minimize the risk of adverse effects and ensure safe use of deferoxamine in individuals with impaired kidney function. It's important for healthcare providers to carefully assess each patient's renal status and consider these adjustments when prescribing deferoxamine therapy.

Desferal (Deferoxamine) Dose adjustment in liver disease:

The manufacturer's labeling for deferoxamine does not include dosage adjustments for individuals with hepatic impairment because this population has not been specifically studied. Therefore, there are no established guidelines for adjusting the dose of deferoxamine based on liver function.

Side effects of Desferal (Deferoxamine):

• Cardiovascular:
  • Flushing
  • Hypotension
  • Shock
  • Tachycardia
• Central Nervous System:
  • Brain Disease (Aluminum Toxicity/Dialysis-Related)
  • Dizziness
  • Headache
  • Neuropathy
  • Paresthesia
  • Seizure
• Dermatologic:
  • Skin Rash
  • Urticaria
• Endocrine & Metabolic:
  • Growth Suppression (Children)
  • Hyperparathyroidism (Aggravated)
  • Hypocalcemia
• Gastrointestinal:
  • Abdominal Distress
  • Abdominal Pain
  • Diarrhea
  • Nausea
  • Vomiting
• Genitourinary:
  • Dysuria
  • Urine Discoloration (Pink, Orange Or Reddish Color)
• Hematologic & Oncologic:
  • Dysplasia
  • Leukopenia
  • Thrombocytopenia
• Hepatic:
  • Hepatic Insufficiency
  • Increased Serum Transaminases
• Hypersensitivity:
  • Anaphylaxis (With Or Without Shock)
  • Angioedema
  • Hypersensitivity
• Infection:
  • Infection (Yersinia Mucormycosis)
• Local:
  • Injection Site Reaction
    • Burning
    • Crust
    • Edema
    • Erythema
    • Eschar
    • Induration
    • Infiltration
    • Irritation
    • Pain
    • Pruritus
    • Swelling
    • Vesicles
    • Wheal Formation
• Neuromuscular & Skeletal:
  • Arthralgia
  • Muscle Spasm
  • Myalgia
• Ophthalmic:
  • Blurred Vision
  • Cataract
  • Chromatopsia
  • Corneal Opacity
  • Decreased Peripheral Vision
  • Decreased Visual Acuity
  • Nocturnal Amblyopia
  • Optic Neuritis
  • Retinal Pigment Changes
  • Scotoma
  • Vision Loss
  • Visual Field Defect
• Otic:
  • Hearing Loss
  • Tinnitus
• Renal:
  • Acute Renal Failure
  • Increased Serum Creatinine
  • Renal Tubular Disease
• Respiratory:
  • Acute Respiratory Distress (Dyspnea, Cyanosis And/Or Interstitial Infiltrates)
  • Asthma
• Miscellaneous:
  • Fever

Contraindications to Desferal (Deferoxamine):

Deferoxamine is contraindicated in individuals who have a known hypersensitivity to deferoxamine or any component of the formulation. Additionally, it is contraindicated in patients with severe renal disease or anuria (lack of urine production).

If someone has experienced an allergic reaction to deferoxamine or its components in the past, they should not use this medication. Similarly, individuals with severe kidney disease or anuria should avoid deferoxamine due to the potential risks associated with its use in these conditions.

Warnings and precautions

Acute respiratory distress syndrome (ARDS).

• Deferoxamine, when given in very high doses through the veins to treat severe iron poisoning or thalassemia, has been linked to a condition called acute respiratory distress syndrome (ARDS).
• This has been observed in both children and adults.
• ARDS is a serious lung problem where the lungs can't supply enough oxygen to the body.
• It's important for healthcare providers to monitor patients closely and use deferoxamine carefully to avoid this complication.

Auditory effects

• Auditory problems like ringing in the ears (tinnitus) and difficulty hearing high-pitched sounds can occur with prolonged use of deferoxamine, especially at high doses or in patients with low levels of ferritin (a protein that stores iron).
• These effects are usually reversible if detected early and if deferoxamine is stopped immediately.
• Elderly patients are more prone to experiencing hearing loss.
• Regular audiology exams are advised for patients on long-term deferoxamine treatment to monitor their hearing health.

Growth Retardation

• High doses of deferoxamine along with low levels of ferritin (a protein that stores iron) can lead to growth retardation, especially in children.
• Growth velocity, which refers to how quickly a child grows, may slow down when taking deferoxamine.
• However, if the dose of deferoxamine is reduced, growth velocity may partially return to its previous rate.
• It's important for healthcare providers to monitor growth carefully in children receiving deferoxamine and adjust the dosage as needed to minimize the risk of growth retardation.

Infection

• Patients with iron overload, such as those receiving deferoxamine treatment, are more vulnerable to infections caused by bacteria like Yersinia enterocolitica and Yersinia pseudotuberculosis.
• Deferoxamine therapy can further increase this risk.
• If a patient on deferoxamine develops an infection, it's essential to stop the therapy until the infection is resolved.
• This precaution helps prevent the infection from worsening or spreading while the patient's immune system fights it off.

Infusion reactions

• Infusion reactions, which can include symptoms like flushing of the skin, low blood pressure (hypotension), hives (urticaria), and even shock, are linked with rapidly giving deferoxamine through an intravenous (IV) infusion.
• To prevent these reactions, deferoxamine should be given slowly through IV infusion, or it can also be given through intramuscular (IM) injection or slow subcutaneous infusion.
• This cautious approach helps minimize the risk of adverse reactions and ensures the safety of the patient during treatment with deferoxamine.

Mucormycosis

• Rare but severe cases of mucormycosis, a serious fungal infection, including instances resulting in death, have been reported with the use of deferoxamine.
• If a patient shows signs or symptoms suggestive of mucormycosis, it's important to stop treatment with deferoxamine immediately.
• This precaution helps prevent the worsening of the infection and allows for prompt medical intervention to manage the condition effectively.

Ocular effects

• Ocular (eye-related) problems like blurred vision, cataracts, corneal opacities, and decreased visual acuity can occur with prolonged use of deferoxamine, especially at high doses or in patients with low ferritin levels (a protein that stores iron).
• Other eye issues may include impaired peripheral, color, and night vision, optic neuritis, retinal pigment abnormalities, retinopathy, scotoma, and visual loss or defects.
• Fortunately, these effects are usually reversible if detected early and if deferoxamine is stopped immediately.
• Elderly patients are more at risk for developing eye disorders.
• To monitor eye health, regular eye exams are recommended for patients receiving long-term deferoxamine treatment.

Effects on the renal system:

• Deferoxamine can affect the kidneys, leading to increases in serum creatinine levels, acute renal failure, and disorders of the renal tubules.
• It's important to monitor changes in renal function while using deferoxamine.
• The good news is that deferoxamine can be removed from the body through dialysis because when it binds with iron, the resulting compound is water-soluble and can be excreted through the kidneys.
• This means that in cases where deferoxamine causes kidney issues, dialysis can help remove it from the body.

Urine discoloration:

• Patients should be informed that their urine may appear pink, reddish, or orange in color while they are taking deferoxamine.
• This discoloration, often referred to as "vin rosé discoloration," is a common and harmless side effect of the medication.
• It occurs because deferoxamine can change the color of the urine, but it does not indicate any serious health problems.
• However, it's essential for healthcare providers to inform patients about this potential side effect to prevent unnecessary concern or alarm.

Aluminum toxicity

• In patients with aluminum toxicity, using deferoxamine as a treatment can potentially lead to low calcium levels (hypocalcemia) and worsen hyperparathyroidism.
• Additionally, in individuals with aluminum-related brain problems receiving dialysis, deferoxamine may cause neurological symptoms, including seizures, and could speed up the onset of dialysis dementia.

Hemochromatosis:

• Deferoxamine is not recommended for the treatment of primary hemochromatosis.
• The preferred treatment for primary hemochromatosis is phlebotomy, which involves regularly removing blood to reduce iron levels in the body.
• Phlebotomy is considered the most effective and commonly used treatment for managing iron overload in primary hemochromatosis.

Deferoxamine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor D (Consider therapy modification)
Ascorbic Acid	May enhance the adverse/toxic effect of Deferoxamine. Left ventricular dysfunction is of particular concern. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function.
Multivitamins/Fluoride (with ADE)	May enhance the adverse/toxic effect of Deferoxamine. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function.
Multivitamins/Minerals (with ADEK, Folate, Iron)	May enhance the adverse/toxic effect of Deferoxamine. Left ventricular dysfunction is of particular concern. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function.
Multivitamins/Minerals (with AE, No Iron)	May enhance the adverse/toxic effect of Deferoxamine. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function.
Prochlorperazine	Deferoxamine may enhance the adverse/toxic effect of Prochlorperazine. Specifically, prolonged loss of consciousness has been reported.

Monitoring parameters:

Monitoring and Tests

• Serum Iron, Ferritin, Total Iron-Binding Capacity (TIBC): Measures iron levels in the blood and the body's ability to transport iron.
• Complete Blood Count (CBC) with Differential: Checks different types of blood cells, including red and white blood cells.
• Renal Function Tests (Serum Creatinine): Assesses kidney function by measuring levels of creatinine in the blood.
• Liver Function Tests: Evaluates liver health through various blood markers.
• Serum Chemistries: Examines different chemicals and minerals in the blood.
• Ophthalmologic Exam: Includes visual acuity tests, fundoscopy (examining the back of the eye), and slit-lamp exam (examining the eye's structures).
• Audiometry: Tests hearing function with long-term treatment.
• Growth and Body Weight in Children: Monitors growth and weight every 3 months.

Urine Discoloration

• When deferoxamine binds with iron, it creates a water-soluble compound called ferrioxamine, which can make urine look dark pink, often called "vin rosé" discoloration. However, this change in urine color is not a sign of treatment effectiveness and should not be used to gauge therapy success.

For Dialysis Patients

• Serum Aluminum: Should be checked yearly, with more frequent checks (every 3 months) for patients taking aluminum-containing medications.

Aluminum-Induced Bone Disease

• Serum aluminum concentration should be measured 2 days after a deferoxamine test dose. A positive result indicates a rise of ≥50 mcg/L, suggesting aluminum-induced bone disease.

How to administer Desferal (Deferoxamine)?

Intravenous (IV) Administration

• Adverse Effects: Urticaria, flushing of the skin, hypotension, and shock have been reported with rapid IV administration. To prevent these, limit the infusion rate to 15 mg/kg/hour.
• Acute Iron Toxicity: IV route is preferred for severe toxicity (e.g., patients in shock). Initially, administer 1,000 mg at 15 mg/kg/hour. Subsequent doses can be given over 4 to 12 hours, not exceeding 125 mg/hour.
• Chronic Iron Overload: Administer over 8 to 12 hours for 5 to 7 days per week, not exceeding 15 mg/kg/hour. Avoid concurrent administration with blood transfusion. Longer infusion times (up to 24 hours) may be needed for severe cardiac iron deposition.

Subcutaneous (SubQ) Administration

• For chronic iron overload, administer over 8 to 12 hours using a portable infusion pump. Longer infusion times (24 hours) may also be used.
• Topical anesthetic or glucocorticoid creams can be used for induration or erythema.

Intramuscular (IM) Administration

• IM route may be used for patients with acute iron toxicity without severe symptoms, but IV route is preferred. It may also be used in the treatment of chronic iron toxicity.

Mechanism of action of Desferal (Deferoxamine):

• Deferoxamine works by binding with trivalent ions, mainly ferric ions, primarily in the vascular space, forming a compound called ferrioxamine.
• This compound is then eliminated in the urine by the kidneys.
• Approximately 100 milligrams of deferoxamine can bind around 8.5 milligrams of free circulating elemental iron, which amounts to 85 milligrams per 1,000 milligram dose.
• However, it doesn't remove iron from transferrin or hemoglobin.
• By binding with cytoplasmic free iron, deferoxamine helps reduce the disruption caused by excess iron on mitochondrial cell membranes and enzyme systems.
• As ferrioxamine is excreted in the urine, it may cause the urine to appear pink, red, or orange in color.

Absorption:

• Well absorbed when administered intramuscularly (IM) or subcutaneously (SubQ).

Distribution:

• Deferoxamine is distributed throughout the body fluids.

Protein Binding:

• Less than 10% of deferoxamine binds to proteins.

Metabolism:

• Metabolized by plasma enzymes.
• Binds with iron to form ferrioxamine, which is an iron complex.

Half-life Elimination:

• Half-life for elimination is 14 hours.
• Plasma half-life ranges from 20 to 30 minutes.

Excretion:

• Primarily excreted in urine, both as unchanged drug and ferrioxamine.
• Some excretion occurs in feces via bile.

International Brands of Deferoxamine:

• Desferal
• PMS-Deferoxamine
• Desferin
• Talifer

Deferoxamine Brand Names in Pakistan:

deferoxamine Injection 500 mg
Desferal	Novartis Pharma (Pak) Ltd

 

deferoxamine Tablets 125 mg
Osveral	Nextar Pharma (Pvt) Ltd.

 

deferoxamine Tablets 250 mg
Osveral	Nextar Pharma (Pvt) Ltd.

 

deferoxamine Tablets 500 mg]
Osveral	Nextar Pharma (Pvt) Ltd.

Deferoxamine is a medication primarily used to treat iron overload caused by blood transfusions in conditions such as thalassemia and hemochromatosis. It belongs to a class of drugs known as iron chelators, which means it binds to excess iron in the bloodstream and helps remove it from the body.

Iron overload can occur in individuals who require frequent blood transfusions, as each transfusion adds additional iron to the body. Over time, this excess iron can accumulate in organs such as the heart, liver, and pancreas, leading to serious complications such as organ damage and failure.

Deferoxamine works by binding to the excess iron and forming a compound that can be excreted from the body through urine and feces. It is typically administered through intravenous infusion or subcutaneous injection.

Desferal (Deferoxamine) is an iron-chelating drug that is used in the treatment of acute and chronic iron overload as in patients with thalassemia. It also binds aluminum and is used in patients on hemodialysis with aluminum toxicity.

Indications of Desferal (Deferoxamine):

• Acute iron toxicity:
  • It is used as an adjunct in the treatment of acute iron intoxication.
• Chronic iron overload:
  • It is indicated for the treatment of chronic iron overload secondary to multiple transfusions (often due to the presence of thalassemia major or sickle cell disease).
• Off Label Use of Deferoxamine in Adults:
  • Diagnosis or treatment of aluminum-induced toxicity associated with chronic kidney disease (CKD).

Desferal (Deferoxamine) dose in adults:

Desferal (Deferoxamine) dose in the treatment of Acute iron toxicity:

In the treatment of acute iron toxicity, the recommended dose of deferoxamine varies based on the severity of toxicity and the route of administration. Here's a typical dosing regimen:

Intravenous (IV) Route:

• Initial dose: 1,000 mg
• Followed by 500 mg every 4 hours for 2 doses
• Subsequent doses of 500 mg may be administered every 4 to 12 hours based on clinical response
• Maximum recommended dose: 6,000 mg per day (as per manufacturer's recommendation)

It's important to note that the IV route is preferred, especially in cases of severe toxicity characterized by cardiovascular collapse, systemic symptoms (such as coma, shock, metabolic acidosis, or gastrointestinal bleeding), or peak serum iron levels exceeding 500 mcg/dL. IV administration allows for rapid and effective delivery of deferoxamine, particularly in critical situations.

Intramuscular (IM) Route:

• IM administration may be used according to the manufacturer's recommendations but is not preferred and rarely indicated.

The use of deferoxamine in situations where the peak serum iron concentration is less than 500 mcg/dL or when severe toxicity is not evident is a subject of clinical debate. Individual patient factors, including the severity of symptoms and the risk of iron toxicity, should be carefully considered when determining the appropriate dosing regimen.

Desferal (Deferoxamine) dose in the treatment of Chronic iron overload:

In the treatment of chronic iron overload, the dosage of deferoxamine can vary depending on the route of administration and individual patient factors. Here are the typical dosing regimens:

Intramuscular (IM) Route:

• Initial dose: 500 to 1,000 mg per day
• Maximum dose: 1,000 mg per day

Intravenous (IV) Route:

• Initial dose: 40 to 50 mg/kg per day
• Maximum dose: 60 mg/kg per day
• Administration duration: Over 8 to 12 hours
• Frequency: 5 to 7 days per week

Subcutaneous (SubQ) Route:

• Initial dose: 1,000 to 2,000 mg per day or 20 to 40 mg/kg per day
• Administration duration: Over 8 to 24 hours

Off-label dosing:

• IV or SubQ: 25 to 50 mg/kg over 8 to 10 hours
• Frequency: 5 to 7 days per week

It's important to note that individual patient factors, including the severity of iron overload and tolerance to the medication, should be considered when determining the appropriate dosage. Close monitoring by healthcare professionals is essential to ensure the safe and effective management of chronic iron overload.

Desferal (Deferoxamine) Dose in the Diagnosis of aluminum-induced toxicity with CKD (off-label use:

In the diagnosis of aluminum-induced toxicity with chronic kidney disease (CKD), particularly in off-label use scenarios, the following deferoxamine dosing regimen may be employed:

Intravenous (IV) Route:

• Test dose: 5 mg/kg during the last hour of dialysis
• Indications for testing:
  • Baseline serum aluminum concentrations are 60 to 200 mcg/L
  • Clinical signs/symptoms of toxicity
  • Aluminum exposure prior to parathyroid surgery
• Measure aluminum just prior to deferoxamine administration
• Remeasure aluminum 2 days later
• Test is considered positive if serum aluminum increases by ≥50 mcg/L
• Do not use if unstimulated aluminum serum concentrations are >200 mcg/L to avoid deferoxamine-induced neurotoxicity.

This dosing regimen aims to assess the response of serum aluminum levels to deferoxamine administration, particularly in patients with CKD who may be at risk of aluminum toxicity due to factors such as dialysis treatment or aluminum exposure from medications or other sources. It's crucial to follow guidelines and recommendations closely to ensure the safe and effective use of deferoxamine in diagnosing aluminum-induced toxicity in CKD patients.

Desferal (Deferoxamine) dose in the treatment of aluminum toxicity with CKD (off-label use):

In the treatment of aluminum toxicity with chronic kidney disease (CKD), particularly in off-label use scenarios, the following deferoxamine dosing regimen may be employed:

Intravenous (IV) Route:

• Administer after diagnostic deferoxamine test dose.
• Note: Do not perform the deferoxamine-stimulation test and administer intensive dialysis until serum aluminum concentrations are <200 mcg/L to avoid the risk of deferoxamine-associated neurotoxicity.

If serum aluminum concentration rises to ≥300 mcg/L two days after the deferoxamine test dose or there are side effects after the deferoxamine-stimulation test:

• Dosage: 5 mg/kg once a week, administered 5 hours before dialysis for 4 months.
• After 4 months: Discontinue deferoxamine for one month and perform the deferoxamine-stimulation test again.

If serum aluminum concentration is <300 mcg/L two days after the deferoxamine test dose and there are no side effects after the deferoxamine-stimulation test:

• Dosage: 5 mg/kg once a week, administered during the last hour of dialysis for 2 months.
• After 2 months: Discontinue deferoxamine for one month and perform the deferoxamine-stimulation test again.

This dosing regimen aims to manage aluminum toxicity in CKD patients while minimizing the risk of deferoxamine-associated neurotoxicity. It involves careful monitoring of serum aluminum concentrations and adjustment of deferoxamine dosage based on the patient's response and tolerance. Close adherence to guidelines and recommendations is essential for the safe and effective treatment of aluminum toxicity in CKD patients.

Desferal Desferal (Deferoxamine) dose in children:

Desferal (Deferoxamine) dose for Acute iron intoxication:

In the treatment of acute iron intoxication, the dosage of deferoxamine varies based on the severity of toxicity and the route of administration. Here are the typical dosing regimens:

Children & Adolescents

Intravenous (IV) Route:

• Continuous IV infusion:
  • Initial dose: 15 mg/kg/hour
  • Maximum daily dose: 80 mg/kg/day, not to exceed 6 g/day
• Initial bolus dose:
  • Initial dose: 20 mg/kg (maximum dose: 1,000 mg) administered no faster than 15 mg/kg/hour
  • Followed by 10 mg/kg (maximum dose: 500 mg) over 4-hour intervals for 2 doses
  • Subsequent doses of 10 mg/kg (maximum dose: 500 mg) over 4 to 12 hours may be repeated depending on clinical response
  • Maximum daily dose: 6 g/day
• IV dosing may also be used if symptoms are not severe

Intramuscular (IM) Route:

• Initial dose: 90 mg/kg/dose for one dose
• Subsequent doses: 45 mg/kg/dose every 4 to 12 hours as needed
• Maximum single dose:
  • Children: 1,000 mg
  • Adults: 2,000 mg
• Maximum daily dose: 6 g/day

It's important to note that individual patient factors, including the severity of symptoms and the risk of iron toxicity, should be considered when determining the appropriate dosage. Close monitoring by healthcare professionals is essential to ensure the safe and effective management of acute iron intoxication.

Desferal (Deferoxamine) dose in Chronic iron overload:

In the treatment of chronic iron overload, the dosage of deferoxamine can vary depending on the route of administration and the age of the patient. Here are the typical dosing regimens:

Intravenous (IV) Route:

• Children and growing adolescents: 20 to 40 mg/kg/day over 8 to 12 hours, 5 to 7 days per week
  • Usual maximum daily dose: 40 mg/kg/day
• Adolescents once growth has ceased: 40 to 50 mg/kg/day over 8 to 12 hours, 5 to 7 days per week
  • Usual maximum daily dose: 60 mg/kg/day

Subcutaneous (SubQ) Route via a portable, controlled infusion device:

• 20 to 40 mg/kg/day over 8 to 12 hours, 3 to 7 days per week
• Maximum daily dose: 2,000 mg/day
• Doses exceeding 60 mg/kg/day have not been shown to provide additional benefit

It's essential to adhere to the recommended dosing guidelines provided by the manufacturer and consider factors such as patient age, growth status, and response to treatment when determining the appropriate dosage of deferoxamine for chronic iron overload. Close monitoring by healthcare professionals is necessary to ensure the safe and effective management of iron overload in pediatric and adolescent patients.

Desferal (Deferoxamine) dose for chronic iron overload in patients with Sickle cell disease:

In the treatment of chronic iron overload in sickle cell disease, particularly in children and adolescents, the typical dosing regimen for deferoxamine is as follows:

Subcutaneous (SubQ) Route:

• Dosage: 25 mg/kg/day
• Administration duration: Over 8 hours
• Dose and duration may be increased as needed based on individual patient response and tolerance

It's essential to closely monitor patients receiving deferoxamine therapy for chronic iron overload, adjusting the dosage and duration as necessary to effectively manage iron levels while minimizing the risk of adverse effects.

Desferal (Deferoxamine) dose in chronic iron overload in patients with Thalassemia:

In the treatment of chronic iron overload in thalassemia, the dosage of deferoxamine varies depending on the age of the patient and their growth status. Here are the typical dosing regimens:

Children and Growing Adolescents:

• Subcutaneous (SubQ) infusion:
  • Dosage: 20 to 40 mg/kg/day over 8 to 12 hours
  • Frequency: 6 to 7 nights per week
  • Maximum daily dose: 40 mg/kg/day

Adolescents once growth has ceased:

• SubQ infusion (preferred):
  • Dosage: 40 to 60 mg/kg/day over 8 to 12 hours
  • Frequency: 6 to 7 nights per week
  • Maximum daily dose: 2,000 mg/day
• SubQ bolus:
  • Dosage: 45 mg/kg/dose
  • Frequency: 5 times per week

It's important to monitor ferritin levels regularly and adjust the deferoxamine dosage as needed to maintain the therapeutic index below 0.025. Additionally, individual patient factors and response to treatment should be considered when determining the appropriate dosage for managing chronic iron overload in thalassemia.

Desferal (Deferoxamine) dose in the treatment of aluminum-induced bone disease in chronic renal failure:

In the treatment of aluminum-induced bone disease in chronic renal failure, particularly in children and adolescents, the dosage of deferoxamine is as follows:

Test (Diagnostic) Dose:

• Intravenous (IV) route: 5 mg/kg as a single dose infused over the last hour of dialysis.
• Serum aluminum concentration should be measured 2 days later.
• Depending on the change in serum aluminum concentration, treatment with deferoxamine may be indicated.

Treatment:

• Monitor serum aluminum levels closely.
• Refer to National Kidney Foundation guidelines for additional details on treatment algorithms.

It's important to note that deferoxamine treatment should only be initiated if serum aluminum concentration is within the intended range of 60 to 200 mcg/L. If serum aluminum concentration exceeds 200 mcg/L, intensive dialysis should be employed until serum aluminum levels decrease below the threshold for chelation therapy.

In the treatment of aluminum serum concentration rise to ≥300 mcg/L or if adverse effects occur with the test dose, the recommended deferoxamine dosage is as follows:

Intravenous (IV) Route:

• Dosage: 5 mg/kg once a week
• Timing: Administered 5 hours before dialysis
• Duration: Treatment should continue for 4 months

For aluminum serum concentration rise to <300 mcg/L, the recommended deferoxamine dosage is:

Intravenous (IV) Route:

• Dosage: 5 mg/kg once a week
• Timing: Administered during the last hour of dialysis
• Duration: Treatment should continue for 2 months

These dosing regimens aim to manage elevated aluminum levels effectively while minimizing the risk of adverse effects associated with deferoxamine therapy. It's crucial to closely monitor serum aluminum concentrations during treatment and adjust the dosage or duration as needed based on the patient's response.

Pregnancy Risk Factor C

• While studies on animals have shown some problems during pregnancy with deferoxamine, it's not clear if it can harm the baby directly.
• However, if a pregnant woman takes too much deferoxamine or iron, it might affect her body in a way that could harm the baby.
• If a pregnant woman has a sudden overdose of iron, she should still get treatment, even though there's a small risk to the baby.

Deferoxamine use during breastfeeding:

• It's uncertain if deferoxamine passes into breast milk.
• One woman who took deferoxamine while breastfeeding had normal levels of iron in her breast milk, and her twins didn't have any reported problems.
• However, caution is still advised when giving deferoxamine to breastfeeding women, according to the manufacturer's recommendation.

Desferal (Deferoxamine) Dose adjustment in renal disease:

For individuals with severe kidney disease or anuria (lack of urine production), the use of deferoxamine is not recommended according to the manufacturer's labeling in the United States.

However, some clinicians have made adjustments based on the patient's kidney function:

• For adults with creatinine clearance (CrCl) greater than 50 mL/minute, no adjustment to the dose of deferoxamine is typically needed.
• For adults with CrCl between 10 to 50 mL/minute or those undergoing continuous renal replacement therapy (CRRT), the dose of deferoxamine may be reduced to 25% to 50% of the normal dose.
• For adults with CrCl less than 10 mL/minute or those undergoing hemodialysis or peritoneal dialysis, the use of deferoxamine should be avoided.

These adjustments aim to minimize the risk of adverse effects and ensure safe use of deferoxamine in individuals with impaired kidney function. It's important for healthcare providers to carefully assess each patient's renal status and consider these adjustments when prescribing deferoxamine therapy.

Desferal (Deferoxamine) Dose adjustment in liver disease:

The manufacturer's labeling for deferoxamine does not include dosage adjustments for individuals with hepatic impairment because this population has not been specifically studied. Therefore, there are no established guidelines for adjusting the dose of deferoxamine based on liver function.

Side effects of Desferal (Deferoxamine):

• Cardiovascular:
  • Flushing
  • Hypotension
  • Shock
  • Tachycardia
• Central Nervous System:
  • Brain Disease (Aluminum Toxicity/Dialysis-Related)
  • Dizziness
  • Headache
  • Neuropathy
  • Paresthesia
  • Seizure
• Dermatologic:
  • Skin Rash
  • Urticaria
• Endocrine & Metabolic:
  • Growth Suppression (Children)
  • Hyperparathyroidism (Aggravated)
  • Hypocalcemia
• Gastrointestinal:
  • Abdominal Distress
  • Abdominal Pain
  • Diarrhea
  • Nausea
  • Vomiting
• Genitourinary:
  • Dysuria
  • Urine Discoloration (Pink, Orange Or Reddish Color)
• Hematologic & Oncologic:
  • Dysplasia
  • Leukopenia
  • Thrombocytopenia
• Hepatic:
  • Hepatic Insufficiency
  • Increased Serum Transaminases
• Hypersensitivity:
  • Anaphylaxis (With Or Without Shock)
  • Angioedema
  • Hypersensitivity
• Infection:
  • Infection (Yersinia Mucormycosis)
• Local:
  • Injection Site Reaction
    • Burning
    • Crust
    • Edema
    • Erythema
    • Eschar
    • Induration
    • Infiltration
    • Irritation
    • Pain
    • Pruritus
    • Swelling
    • Vesicles
    • Wheal Formation
• Neuromuscular & Skeletal:
  • Arthralgia
  • Muscle Spasm
  • Myalgia
• Ophthalmic:
  • Blurred Vision
  • Cataract
  • Chromatopsia
  • Corneal Opacity
  • Decreased Peripheral Vision
  • Decreased Visual Acuity
  • Nocturnal Amblyopia
  • Optic Neuritis
  • Retinal Pigment Changes
  • Scotoma
  • Vision Loss
  • Visual Field Defect
• Otic:
  • Hearing Loss
  • Tinnitus
• Renal:
  • Acute Renal Failure
  • Increased Serum Creatinine
  • Renal Tubular Disease
• Respiratory:
  • Acute Respiratory Distress (Dyspnea, Cyanosis And/Or Interstitial Infiltrates)
  • Asthma
• Miscellaneous:
  • Fever

Contraindications to Desferal (Deferoxamine):

Deferoxamine is contraindicated in individuals who have a known hypersensitivity to deferoxamine or any component of the formulation. Additionally, it is contraindicated in patients with severe renal disease or anuria (lack of urine production).

If someone has experienced an allergic reaction to deferoxamine or its components in the past, they should not use this medication. Similarly, individuals with severe kidney disease or anuria should avoid deferoxamine due to the potential risks associated with its use in these conditions.

Warnings and precautions

Acute respiratory distress syndrome (ARDS).

• Deferoxamine, when given in very high doses through the veins to treat severe iron poisoning or thalassemia, has been linked to a condition called acute respiratory distress syndrome (ARDS).
• This has been observed in both children and adults.
• ARDS is a serious lung problem where the lungs can't supply enough oxygen to the body.
• It's important for healthcare providers to monitor patients closely and use deferoxamine carefully to avoid this complication.

Auditory effects

• Auditory problems like ringing in the ears (tinnitus) and difficulty hearing high-pitched sounds can occur with prolonged use of deferoxamine, especially at high doses or in patients with low levels of ferritin (a protein that stores iron).
• These effects are usually reversible if detected early and if deferoxamine is stopped immediately.
• Elderly patients are more prone to experiencing hearing loss.
• Regular audiology exams are advised for patients on long-term deferoxamine treatment to monitor their hearing health.

Growth Retardation

• High doses of deferoxamine along with low levels of ferritin (a protein that stores iron) can lead to growth retardation, especially in children.
• Growth velocity, which refers to how quickly a child grows, may slow down when taking deferoxamine.
• However, if the dose of deferoxamine is reduced, growth velocity may partially return to its previous rate.
• It's important for healthcare providers to monitor growth carefully in children receiving deferoxamine and adjust the dosage as needed to minimize the risk of growth retardation.

Infection

• Patients with iron overload, such as those receiving deferoxamine treatment, are more vulnerable to infections caused by bacteria like Yersinia enterocolitica and Yersinia pseudotuberculosis.
• Deferoxamine therapy can further increase this risk.
• If a patient on deferoxamine develops an infection, it's essential to stop the therapy until the infection is resolved.
• This precaution helps prevent the infection from worsening or spreading while the patient's immune system fights it off.

Infusion reactions

• Infusion reactions, which can include symptoms like flushing of the skin, low blood pressure (hypotension), hives (urticaria), and even shock, are linked with rapidly giving deferoxamine through an intravenous (IV) infusion.
• To prevent these reactions, deferoxamine should be given slowly through IV infusion, or it can also be given through intramuscular (IM) injection or slow subcutaneous infusion.
• This cautious approach helps minimize the risk of adverse reactions and ensures the safety of the patient during treatment with deferoxamine.

Mucormycosis

• Rare but severe cases of mucormycosis, a serious fungal infection, including instances resulting in death, have been reported with the use of deferoxamine.
• If a patient shows signs or symptoms suggestive of mucormycosis, it's important to stop treatment with deferoxamine immediately.
• This precaution helps prevent the worsening of the infection and allows for prompt medical intervention to manage the condition effectively.

Ocular effects

• Ocular (eye-related) problems like blurred vision, cataracts, corneal opacities, and decreased visual acuity can occur with prolonged use of deferoxamine, especially at high doses or in patients with low ferritin levels (a protein that stores iron).
• Other eye issues may include impaired peripheral, color, and night vision, optic neuritis, retinal pigment abnormalities, retinopathy, scotoma, and visual loss or defects.
• Fortunately, these effects are usually reversible if detected early and if deferoxamine is stopped immediately.
• Elderly patients are more at risk for developing eye disorders.
• To monitor eye health, regular eye exams are recommended for patients receiving long-term deferoxamine treatment.

Effects on the renal system:

• Deferoxamine can affect the kidneys, leading to increases in serum creatinine levels, acute renal failure, and disorders of the renal tubules.
• It's important to monitor changes in renal function while using deferoxamine.
• The good news is that deferoxamine can be removed from the body through dialysis because when it binds with iron, the resulting compound is water-soluble and can be excreted through the kidneys.
• This means that in cases where deferoxamine causes kidney issues, dialysis can help remove it from the body.

Urine discoloration:

• Patients should be informed that their urine may appear pink, reddish, or orange in color while they are taking deferoxamine.
• This discoloration, often referred to as "vin rosé discoloration," is a common and harmless side effect of the medication.
• It occurs because deferoxamine can change the color of the urine, but it does not indicate any serious health problems.
• However, it's essential for healthcare providers to inform patients about this potential side effect to prevent unnecessary concern or alarm.

Aluminum toxicity

• In patients with aluminum toxicity, using deferoxamine as a treatment can potentially lead to low calcium levels (hypocalcemia) and worsen hyperparathyroidism.
• Additionally, in individuals with aluminum-related brain problems receiving dialysis, deferoxamine may cause neurological symptoms, including seizures, and could speed up the onset of dialysis dementia.

Hemochromatosis:

• Deferoxamine is not recommended for the treatment of primary hemochromatosis.
• The preferred treatment for primary hemochromatosis is phlebotomy, which involves regularly removing blood to reduce iron levels in the body.
• Phlebotomy is considered the most effective and commonly used treatment for managing iron overload in primary hemochromatosis.

Deferoxamine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor D (Consider therapy modification)
Ascorbic Acid	May enhance the adverse/toxic effect of Deferoxamine. Left ventricular dysfunction is of particular concern. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function.
Multivitamins/Fluoride (with ADE)	May enhance the adverse/toxic effect of Deferoxamine. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function.
Multivitamins/Minerals (with ADEK, Folate, Iron)	May enhance the adverse/toxic effect of Deferoxamine. Left ventricular dysfunction is of particular concern. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function.
Multivitamins/Minerals (with AE, No Iron)	May enhance the adverse/toxic effect of Deferoxamine. Management: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally soon after setting up the infusion pump. Monitor cardiac function.
Prochlorperazine	Deferoxamine may enhance the adverse/toxic effect of Prochlorperazine. Specifically, prolonged loss of consciousness has been reported.

Monitoring parameters:

Monitoring and Tests

• Serum Iron, Ferritin, Total Iron-Binding Capacity (TIBC): Measures iron levels in the blood and the body's ability to transport iron.
• Complete Blood Count (CBC) with Differential: Checks different types of blood cells, including red and white blood cells.
• Renal Function Tests (Serum Creatinine): Assesses kidney function by measuring levels of creatinine in the blood.
• Liver Function Tests: Evaluates liver health through various blood markers.
• Serum Chemistries: Examines different chemicals and minerals in the blood.
• Ophthalmologic Exam: Includes visual acuity tests, fundoscopy (examining the back of the eye), and slit-lamp exam (examining the eye's structures).
• Audiometry: Tests hearing function with long-term treatment.
• Growth and Body Weight in Children: Monitors growth and weight every 3 months.

Urine Discoloration

• When deferoxamine binds with iron, it creates a water-soluble compound called ferrioxamine, which can make urine look dark pink, often called "vin rosé" discoloration. However, this change in urine color is not a sign of treatment effectiveness and should not be used to gauge therapy success.

For Dialysis Patients

• Serum Aluminum: Should be checked yearly, with more frequent checks (every 3 months) for patients taking aluminum-containing medications.

Aluminum-Induced Bone Disease

• Serum aluminum concentration should be measured 2 days after a deferoxamine test dose. A positive result indicates a rise of ≥50 mcg/L, suggesting aluminum-induced bone disease.

How to administer Desferal (Deferoxamine)?

Intravenous (IV) Administration

• Adverse Effects: Urticaria, flushing of the skin, hypotension, and shock have been reported with rapid IV administration. To prevent these, limit the infusion rate to 15 mg/kg/hour.
• Acute Iron Toxicity: IV route is preferred for severe toxicity (e.g., patients in shock). Initially, administer 1,000 mg at 15 mg/kg/hour. Subsequent doses can be given over 4 to 12 hours, not exceeding 125 mg/hour.
• Chronic Iron Overload: Administer over 8 to 12 hours for 5 to 7 days per week, not exceeding 15 mg/kg/hour. Avoid concurrent administration with blood transfusion. Longer infusion times (up to 24 hours) may be needed for severe cardiac iron deposition.

Subcutaneous (SubQ) Administration

• For chronic iron overload, administer over 8 to 12 hours using a portable infusion pump. Longer infusion times (24 hours) may also be used.
• Topical anesthetic or glucocorticoid creams can be used for induration or erythema.

Intramuscular (IM) Administration

• IM route may be used for patients with acute iron toxicity without severe symptoms, but IV route is preferred. It may also be used in the treatment of chronic iron toxicity.

Mechanism of action of Desferal (Deferoxamine):

• Deferoxamine works by binding with trivalent ions, mainly ferric ions, primarily in the vascular space, forming a compound called ferrioxamine.
• This compound is then eliminated in the urine by the kidneys.
• Approximately 100 milligrams of deferoxamine can bind around 8.5 milligrams of free circulating elemental iron, which amounts to 85 milligrams per 1,000 milligram dose.
• However, it doesn't remove iron from transferrin or hemoglobin.
• By binding with cytoplasmic free iron, deferoxamine helps reduce the disruption caused by excess iron on mitochondrial cell membranes and enzyme systems.
• As ferrioxamine is excreted in the urine, it may cause the urine to appear pink, red, or orange in color.

Absorption:

• Well absorbed when administered intramuscularly (IM) or subcutaneously (SubQ).

Distribution:

• Deferoxamine is distributed throughout the body fluids.

Protein Binding:

• Less than 10% of deferoxamine binds to proteins.

Metabolism:

• Metabolized by plasma enzymes.
• Binds with iron to form ferrioxamine, which is an iron complex.

Half-life Elimination:

• Half-life for elimination is 14 hours.
• Plasma half-life ranges from 20 to 30 minutes.

Excretion:

• Primarily excreted in urine, both as unchanged drug and ferrioxamine.
• Some excretion occurs in feces via bile.

International Brands of Deferoxamine:

• Desferal
• PMS-Deferoxamine
• Desferin
• Talifer

Deferoxamine Brand Names in Pakistan:

deferoxamine Injection 500 mg
Desferal	Novartis Pharma (Pak) Ltd

 

deferoxamine Tablets 125 mg
Osveral	Nextar Pharma (Pvt) Ltd.

 

deferoxamine Tablets 250 mg
Osveral	Nextar Pharma (Pvt) Ltd.

 

deferoxamine Tablets 500 mg]
Osveral	Nextar Pharma (Pvt) Ltd.