Ferric Carboxymaltose

Usage

Ferric Carboxymaltose is indicated for the treatment of iron deficiency anemia (IDA) when oral iron preparations are ineffective, cannot be used, or there’s a clinical need for rapid iron delivery. Specifically, it is used in adults and children 1 year and older with IDA who have intolerance to oral iron or haven’t responded well to it. It is also used for iron deficiency in adults with heart failure (New York Heart Association class II/III) to improve exercise capacity and in adults with non-dialysis-dependent chronic kidney disease (CKD). The diagnosis of iron deficiency must be based on laboratory tests.

It is pharmacologically classified as an iron replacement product.

Ferric carboxymaltose provides a controlled delivery of iron to transferrin and ferritin, the body’s iron transport and storage proteins, respectively. This replenishes iron stores, enabling the production of red blood cells and improving hemoglobin levels.

Alternate Names

International Nonproprietary Name (INN): Ferric Carboxymaltose

Brand names: Injectafer®, Ferinject® (other regional brand names may exist)

How It Works

Pharmacodynamics: Ferric carboxymaltose dissociates, releasing iron for binding to transferrin and incorporation into hemoglobin within red blood cells. This increases oxygen-carrying capacity and alleviates symptoms of iron deficiency anemia, including fatigue and shortness of breath. In patients with heart failure, improved exercise capacity is observed with treatment.

Pharmacokinetics: Following intravenous administration, ferric carboxymaltose is rapidly cleared from the plasma, with iron being taken up by the reticuloendothelial system. The iron is then incorporated into hemoglobin for red blood cell production or stored as ferritin. Minimal iron excretion occurs through the kidneys.

Mode of Action: Ferric carboxymaltose provides iron in a non-ionic, carbohydrate-complexed form, which minimizes the risk of free iron toxicity. The complex dissociates, releasing iron for binding to transferrin, the iron transport protein, and subsequent utilization in erythropoiesis.

Elimination: Iron administered as ferric carboxymaltose undergoes minimal excretion. Excess iron can be stored as ferritin or hemosiderin, primarily in the liver, spleen, and bone marrow.

Dosage

Standard Dosage

Adults:

• IDA: 750 mg administered intravenously in two doses separated by at least 7 days (total cumulative dose of 1500 mg per course). Alternatively, a single dose of 15 mg/kg (up to a maximum of 1000 mg) can be administered.
• Heart Failure: Single doses of 15mg/kg (up to a maximum single dose of 1000mg) may be administered every 6 weeks up to a maximum of 5 doses.
• Patients weighing <50kg: 15 mg/kg IV in 2 doses separated by at least 7 days per course.

Children (1 year and older):

• IDA: 15 mg/kg IV in two doses separated by at least 7 days per course.

Special Cases:

• Elderly Patients: No specific dose adjustment is recommended based solely on age. However, monitor closely for potential adverse effects and adjust dose based on renal function.
• Patients with Renal Impairment: Caution is advised, particularly for patients on dialysis. Dosage adjustments may be necessary based on individual patient needs.
• Patients with Hepatic Dysfunction: Caution advised; monitor closely for adverse events.
• Patients with Comorbid Conditions: Individualized dosing based on clinical assessment and patient tolerance.

Clinical Use Cases Dosages for clinical situations like intubation, surgical procedures, mechanical ventilation, and ICU or emergency use should follow the standard dosing guidelines for IDA, with adjustments based on individual patient needs.

Dosage Adjustments

Adjustments might be necessary in patients with impaired renal or hepatic function, metabolic disorders, or genetic polymorphisms affecting drug metabolism. Dose calculation should be done by a treating Medical Officer and must not exceed 20 mg/kg or 1000 mg per week.

Side Effects

Common Side Effects

Nausea, dizziness, flushing, hypotension, hypertension, injection site reactions (pain, irritation, bruising), headache, vomiting, changes in taste, fatigue.

Rare but Serious Side Effects

Hypersensitivity reactions (including anaphylaxis), hypophosphatemia (bone pain, muscle weakness, mental/mood changes), dyspnea, rash, urticaria.

Long-Term Effects

Iron overload (haemosiderosis) with repeated high doses. Regular monitoring of iron indices (ferritin, transferrin saturation) is required.

Adverse Drug Reactions (ADR)

Anaphylaxis, severe hypophosphatemia, clinically significant hypertension.

Contraindications

• Hypersensitivity to ferric carboxymaltose or any of its components.
• Anemia not caused by iron deficiency (e.g., hemolytic anemia, megaloblastic anemia).
• Known iron overload (e.g., hemochromatosis, hemosiderosis).

Drug Interactions

• Oral iron: Oral iron absorption can be decreased, so administration should be separated by at least 5 days.
• Phosphate binders: Ferric carboxymaltose can interfere with the absorption of phosphate binders.
• Other iron-containing products: Concomitant use may increase the risk of iron overload.
• Dimercaprol: Concurrent administration should be avoided.

Pregnancy and Breastfeeding

• Pregnancy: Use only if clearly needed and the benefits outweigh the potential risks to the fetus. Data is limited, especially for the first trimester. Consult with an obstetrician. Generally, use is recommended only after 16 weeks of gestation if clearly needed.
• Breastfeeding: Transfer of iron into breast milk is negligible. However, caution is advised. Monitor infants for potential gastrointestinal adverse reactions.

Drug Profile Summary

• Mechanism of Action: Replenishes iron stores by supplying iron for transport to transferrin and storage in ferritin.
• Side Effects: Nausea, dizziness, flushing, injection site reactions, hypotension, hypertension; rarely, hypersensitivity reactions and hypophosphatemia.
• Contraindications: Hypersensitivity, anemia not due to iron deficiency, iron overload.
• Drug Interactions: Oral iron, phosphate binders, other iron-containing products.
• Pregnancy & Breastfeeding: Use with caution; limited safety data for the first trimester of pregnancy.
• Dosage: Adult IDA: 750 mg IV in two doses separated by at least 7 days (total 1500 mg); alternatively, a single dose of up to 1000 mg can be administered based on weight (15 mg/kg). Pediatric: 15 mg/kg IV in two doses separated by at least 7 days. Special adjustments may be necessary.
• Monitoring Parameters: Hemoglobin, ferritin, transferrin saturation, blood pressure, signs of hypersensitivity.

Popular Combinations

Ferric carboxymaltose is generally used as monotherapy. Concomitant use with erythropoiesis-stimulating agents may be considered in some cases of CKD-related anemia under specialist guidance.

Precautions

• General Precautions: Screen for allergies, assess renal and hepatic function, monitor blood pressure.
• Specific Populations:
  • Pregnant Women: Assess risks/benefits carefully. Use generally recommended only after 16 weeks gestation.
  • Breastfeeding Mothers: Monitor infant for potential gastrointestinal issues.
  • Children & Elderly: Follow age-specific dosing guidelines and monitor closely for adverse events.
• Lifestyle Considerations: Alcohol and dietary interactions are not clinically significant. Driving restrictions are not routinely necessary unless dizziness or hypotension occurs.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ferric Carboxymaltose?

A: For adults with IDA weighing >50 kg, 750 mg IV in two doses separated by at least 7 days (total 1500 mg) or a single dose of 15 mg/kg (up to 1000 mg). For children 1 year and older and adults <50 kg, 15 mg/kg IV in two doses separated by at least 7 days. For adults with heart failure, single doses of 15mg/kg (max 1000mg) can be administered every 6 weeks (max 5 doses).

Q2: What are the main side effects of Ferric Carboxymaltose?

A: Common side effects include nausea, dizziness, flushing, injection site reactions, hypotension, hypertension, headache, and vomiting. Rare but serious side effects include hypersensitivity reactions and hypophosphatemia.

Q3: How is Ferric Carboxymaltose administered?

A: It’s administered intravenously, either as an infusion or bolus injection, under the supervision of a healthcare professional.

Q4: Who should not receive Ferric Carboxymaltose?

A: Contraindications include hypersensitivity to the drug, anemia not caused by iron deficiency, and iron overload conditions.

Q5: Can Ferric Carboxymaltose be used in pregnancy?

A: Use with caution and only if clearly needed. Data is limited for the first trimester, and it’s generally recommended to restrict use to after 16 weeks gestation. Consult an obstetrician.

Q6: How should I monitor patients receiving Ferric Carboxymaltose?

A: Monitor hemoglobin, ferritin, transferrin saturation, blood pressure, and any signs of hypersensitivity reactions.

Q7: What are the signs of a hypersensitivity reaction to Ferric Carboxymaltose?

A: Signs may include rash, itching, swelling (especially of the face, tongue, or throat), difficulty breathing, chest pain, and dizziness or lightheadedness.

Q8: What is the maximum single dose of Ferric Carboxymaltose?

A: The maximum single dose is 1000 mg or 20 mg/kg, whichever is lower.

Q9: What are the key differences between Ferric Carboxymaltose and other intravenous iron preparations?

A: Ferric Carboxymaltose allows for higher single doses and fewer administrations compared to other intravenous iron formulations like iron sucrose. It also has a lower risk of hypersensitivity reactions compared to high molecular weight iron dextran.

Q10: How is iron deficiency anemia diagnosed?

A: Diagnosis involves laboratory tests such as complete blood count (CBC), serum ferritin, transferrin saturation, and iron levels to assess iron stores and red blood cell parameters.