Ferric Carboxymaltose Injection

Introduction Overview

Generic Name

ferric carboxymaltose injection

Brand Name

Injectafer

Dosage Form

Injection for intravenous use

Drug Class

Iron products

Pharmacokinetics

Absorption:
Injectafer is administered intravenously, ensuring 100% bioavailability with direct delivery of elemental iron into the bloodstream. This bypasses the gastrointestinal tract, thereby avoiding the absorption limitations and gastrointestinal side effects associated with oral iron supplements. The rapid availability of iron supports quick replenishment of iron stores in patients with iron deficiency anemia (IDA).

Distribution:
After intravenous administration, ferric carboxymaltose distributes primarily into the reticuloendothelial system, including macrophages in the spleen, liver, and bone marrow. The iron is released slowly from the carbohydrate complex, providing a stable and controlled release, which minimizes free iron and reduces the risk of oxidative stress. The distribution is influenced by the extent of iron deficiency and the body's need for erythropoiesis.

Metabolism:
Ferric carboxymaltose functions as a prodrug delivering iron in a complexed form. Once in the reticuloendothelial system, the iron-carbohydrate complex is taken up by macrophages, and iron is released from the complex and incorporated into the body's iron pool. Unlike free iron, the complex is designed to slowly release iron, which minimizes acute toxicity. The metabolism involves the hydrolysis and breakdown of the carbohydrate moiety and subsequent incorporation of iron into hemoglobin and storage proteins such as ferritin.

Elimination:
Excess iron not immediately utilized for hemoglobin synthesis is stored primarily as ferritin or hemosiderin, mainly in the liver, spleen, and bone marrow. There is no active excretion of iron from the body; elimination occurs mainly through desquamation of intestinal mucosal cells, minor bleeding, and parenteral losses. The controlled release nature reduces the likelihood of iron overload compared to free iron administration, but monitoring is crucial to prevent iron accumulation especially in patients with iron overload disorders.

Clinical Implications:
The pharmacokinetics of Injectafer allows for rapid correction of iron deficiency anemia with fewer administrations compared to oral iron. Its controlled-release profile permits large single doses, which improves patient compliance, especially in patients intolerant to oral iron or with malabsorption issues. The product's pharmacokinetic profile also requires monitoring of phosphate levels and blood pressure to manage potential adverse effects.

Dosage Forms

Available Dosage Forms:
Injectafer is supplied as an intravenous injectable solution with three vial sizes:
- 100 mg elemental iron per 2 mL single-dose vial
- 750 mg elemental iron per 15 mL single-dose vial
- 1,000 mg elemental iron per 20 mL single-dose vial
The solution is intended for intravenous use and contains ferric carboxymaltose as the active ingredient with a concentration of 50 mg of elemental iron per mL.

Dosages for Adults and Adolescents:
- For individuals weighing 50 kg or more: two doses of 750 mg elemental iron each given via slow intravenous push or infusion separated by at least 7 days.
- For individuals weighing less than 50 kg: two doses of 15 mg/kg elemental iron via slow intravenous push or infusion separated by at least 7 days.
- The maximum cumulative dose per treatment course should not exceed 1500 mg elemental iron.
- For iron deficiency associated with mild to moderate heart failure (NYHA class II/III), dosing is individualized based on weight and hemoglobin levels, and injections are administered 6 weeks apart.

Specific Patient Populations:
- Pediatric use: Approved for children aged 1 year and older with iron deficiency anemia who have intolerance to or an unsatisfactory response to oral iron supplements.
- Patients with non-dialysis dependent chronic kidney disease: Indicated for iron deficiency anemia treatment.
- Pregnant and breastfeeding women: Use only if benefits outweigh the risks; careful monitoring is needed due to potential risks to the fetus or infant.
- Patients with a history of hypersensitivity to ferric carboxymaltose or any inactive ingredients should avoid use.
- Patients with iron overload disorders or anemia not caused by iron deficiency are contraindicated for Injectafer use.

Administration Details:
Injectafer is administered either as an undiluted slow intravenous push or by intravenous infusion over at least 15 minutes. Patients are observed during administration and for at least 30 minutes afterward for hypersensitivity reactions. The dosing frequency, intervals, and cumulative dose should be individualized per clinical guidelines and patient response.

Mechanism Of Action

Injectafer (ferric carboxymaltose) is an intravenous iron replacement therapy that exerts its therapeutic effect by replenishing depleted iron stores necessary for hemoglobin synthesis and erythropoiesis. The ferric carboxymaltose complex consists of a ferric hydroxide core stabilized by a carboxymaltose carbohydrate shell, which allows the delivery of a high dose of iron in a controlled and stable formulation.

Upon intravenous administration, Injectafer circulates in the bloodstream where macrophages of the reticuloendothelial system recognize and uptake the ferric carboxymaltose complex. The carbohydrate shell is metabolized intracellularly, releasing free iron ions that are then transported into the plasma and utilized in the synthesis of hemoglobin and other iron-dependent proteins.

At the cellular level, iron is critical in the mitochondrial synthesis of heme groups, an essential component of hemoglobin that facilitates oxygen transport. Injectafer's controlled iron release reduces free iron-mediated oxidative damage and limits inflammatory responses compared to less stable iron complexes. This targeted delivery minimizes the risk of adverse effects related to free iron, such as generation of reactive oxygen species.

Clinically, Injectafer's mechanism translates into rapid correction of iron deficiency anemia by bypassing gastrointestinal absorption barriers and delivering bioavailable iron directly into the systemic circulation. This is particularly beneficial in patients with oral iron intolerance, malabsorption syndromes, or when rapid iron repletion is critical. Comparative studies show Injectafer providing effective iron repletion with fewer doses and lower rates of gastrointestinal adverse effects than oral iron formulations and some alternative intravenous iron therapies.

Pharmacological Actions

Rapid intravenous replenishment of iron stores in patients with iron deficiency anemia.
Controlled release of elemental iron to minimize free iron-related oxidative stress.
Stimulation of erythropoiesis by providing essential iron required for hemoglobin synthesis.
Bypasses gastrointestinal absorption limitations associated with oral iron therapies.
Reduction in symptoms of iron deficiency anemia such as fatigue and impaired cognitive function.
Improvement in oxygen transport capacity and tissue oxygenation.
Reduction of iron deficiency-related complications in chronic kidney disease and heart failure patients.
Stabilization of iron delivery to the reticuloendothelial system and targeted uptake by macrophages.
Lower risk of gastrointestinal adverse effects compared to oral iron supplementation.
Facilitation of improved exercise capacity in adults with iron deficiency and NYHA class II/III heart failure.
Potential to reduce the frequency of dosing due to high-dose administration capability.
Minimal release of labile plasma iron reducing risk of toxicity.
Enhancement of patient compliance through rapid and effective iron administration.
Provision of a safe alternative option for patients intolerant to oral iron products.

Therapeutic Or Clinical Uses

Treatment of iron deficiency anemia in adults and children aged 1 year and older intolerant to or unresponsive to oral iron therapy.
Treatment of iron deficiency anemia in adults with non-dialysis dependent chronic kidney disease.
Improvement of exercise capacity in adults with iron deficiency and New York Heart Association (NYHA) class II/III heart failure.
Replenishment of iron stores in patients requiring rapid correction of iron deficiency.
Management of anemia where oral iron is contraindicated due to gastrointestinal issues.
Treatment of iron deficiency anemia secondary to inflammatory bowel disease or malabsorption disorders.
Supportive therapy for anemia in pregnancy when oral iron is inadequate or not tolerated, under careful monitoring.
Correction of iron deficiency anemia in patients undergoing surgery or those with chronic blood loss.
Management of iron deficiency anemia in patients with chronic diseases requiring parenteral iron supplementation.
Use in patients with iron deficiency anemia who have previously failed or not tolerated oral iron therapy.
Provision of a treatment option for rapid repletion in preoperative anemia management.
Treatment of iron deficiency conditions where oral therapy compliance is poor.
Use in therapeutic protocols aiming to improve quality of life by correcting anemia-related symptoms.
Adjunctive therapy in patients with chronic conditions exacerbated by iron deficiency.

Side Or Adverse Effects

Hypersensitivity reactions including anaphylaxis, occurring during or immediately after administration.
Transient increase in blood pressure post-injection, with symptoms such as headache, dizziness, and flushing.
Injection site reactions including pain, redness, swelling, or burning sensation.
Nausea and dizziness reported commonly in treated patients.
Headache and flushing characterized by warmth, redness, or tingling sensations.
Phosphorus depletion (hypophosphatemia) potentially leading to fatigue, bone pain, muscle weakness, and fractures.
Rash and other dermatological reactions post-administration.
Potential iron overload with symptoms such as joint and abdominal pain, irregular heartbeats, and weight loss if cumulative dosing is excessive.
Possible gastrointestinal symptoms transmitted via breast milk, including diarrhea or constipation in nursing infants.
Rare risk of serious hypersensitivity necessitating monitoring for at least 30 minutes post-administration.
Fatigue and malaise associated with hypophosphatemia in susceptible patients.
Uncommon allergic reactions like hives, throat swelling, or breathing difficulties requiring emergency treatment.
Local infusion site discomfort during or shortly after administration.
Potential transient elevation in liver enzymes noted in some patients.
Generalized systemic reactions such as fever or chills in rare cases.

Precautions

Monitor patients closely for hypersensitivity or anaphylactic reactions during and after injection.
Avoid administration in patients with known iron overload disorders or anemia not caused by iron deficiency.
Assess serum phosphate levels in patients at risk for hypophosphatemia during treatment.
Use cautiously in patients with a history of allergies to iron products or injectable formulations.
Pregnant and breastfeeding women should use Injectafer only if benefits outweigh potential risks; monitor fetal and infant outcomes closely.
Observe for signs of increased blood pressure and manage accordingly during therapy.
Inform healthcare providers of all concomitant medications to avoid potential drug interactions.
Use caution in patients with impaired vitamin D metabolism, inflammatory bowel disease, or hyperparathyroidism due to altered phosphate handling.
Do not exceed the recommended cumulative dose of 1500 mg elemental iron per treatment course to minimize risk of iron overload.
Discontinue use immediately if severe hypersensitivity reaction occurs.
Injectafer should only be administered by healthcare professionals equipped to manage hypersensitivity reactions.
Repeated dosing may be required; monitor iron indices and clinical response regularly.
Avoid coadministration with other iron-containing preparations unless specifically directed by a physician.
Careful assessment needed in patients with cardiovascular risk due to transient blood pressure elevations.
Educate patients to report symptoms of hypophosphatemia such as bone pain or muscle weakness promptly.

Warnings

Serious hypersensitivity reactions including life-threatening anaphylaxis can occur; patient monitoring during and after administration is mandatory.
Injectafer may cause hypophosphatemia which can lead to serious complications such as osteomalacia and fractures if untreated.
Administration may result in acute elevations in blood pressure; appropriate monitoring and management are necessary.
Not recommended for use in patients with iron overload disorders, as excess iron can cause tissue damage.
Use is contraindicated in anemia not caused by iron deficiency, as treatment will not be beneficial and may cause harm.
Safety and efficacy in children under 1 year of age with iron deficiency anemia have not been established.
Potential harm to the fetus exists if used during pregnancy; benefits must outweigh risks.
Interactions with other medications can alter drug efficacy or increase adverse effects; comprehensive medication review is critical.
Patients should be observed for at least 30 minutes post-injection to detect early signs of allergic or infusion reactions.
Risk of hypersensitivity is increased in patients with a history of allergies to iron or other intravenous medications.
Risk of iron overload and toxicity if dosing exceeds recommended maximum cumulative dose.
Avoid use in patients with active infections or elevated markers of inflammation unless iron deficiency is documented and treatment is necessary.
Patients with conditions affecting phosphate metabolism should be closely monitored to prevent serious hypophosphatemia-related complications.
Educate patients to avoid non-prescribed iron supplements during therapy to prevent iron excess.
Discontinue therapy promptly if severe adverse reactions or signs of iron overload develop.

Contraindication

Known hypersensitivity to ferric carboxymaltose or any inactive ingredients in Injectafer.
Patients with iron overload syndromes such as hemochromatosis.
Anemia of non-iron deficiency etiology including anemia of chronic disease without iron deficiency.
Individuals with a history of allergic reactions to intravenous iron preparations.
Patients under 1 year of age due to unknown safety and efficacy in this population.
Concurrent treatment with other parenteral iron formulations unless carefully managed.
Severe active infections where iron administration may exacerbate microbial proliferation.
Pregnancy unless benefits clearly outweigh the risks due to potential fetal harm.
Breastfeeding mothers unless benefit outweighs the potential risk to the infant.
Unexplained anemia without established iron deficiency.
Patients who have previously demonstrated intolerance or hypersensitivity to Injectafer.
Individuals with elevated serum ferritin indicating iron overload.
Use with caution in patients with severe hepatic impairment where iron metabolism may be altered.
Prior history of Stevens-Johnson syndrome or severe cutaneous adverse reactions to iron products.
Patients with unresolved vitamin D deficiency or multiple metabolic bone disorders without appropriate management.

Drug Interactions

Concomitant use with oral iron supplements may alter absorption or increase risk of iron toxicity; should be avoided unless directed.
Concurrent administration with drugs affecting phosphate metabolism (e.g., phosphate binders, vitamin D analogs) requires monitoring due to risk of hypophosphatemia.
Iron-containing products may reduce absorption of certain antibiotics such as tetracyclines and fluoroquinolones if oral formulations are co-administered.
Potential interaction with antihypertensive medications due to transient post-injection blood pressure elevations.
Use with methotrexate or other immunosuppressants may require dose adjustments due to altered iron status affecting drug metabolism.
Coadministration with bisphosphonates might impact mineral metabolism; clinical monitoring advisable.
Antacids or proton pump inhibitors may influence oral iron absorption but are less relevant to intravenous Injectafer dosing; however, patient history should still be considered.
Avoid simultaneous intravenous administration with calcium or magnesium salts to prevent precipitation.
Potential influence on the pharmacokinetics of drugs relying on iron-dependent enzymes should be considered.
Herbal supplements containing iron or agents affecting iron metabolism should be disclosed to healthcare providers.
Interactions with erythropoiesis-stimulating agents may necessitate dose optimization depending on hematologic response.
Drugs altering gastrointestinal pH or motility may have indirect effects on systemic iron homeostasis if used concomitantly.
Caution when used with anticoagulants or antiplatelet agents due to altered bleeding risk in iron deficiency states.
Monitoring liver function and metabolic status is recommended when combining Injectafer with hepatically metabolized medications.
Patients should provide a comprehensive list of medications to avoid unnoticed interactions.

Preparations Of The Drug

Injectafer is available as a sterile, non-pyrogenic solution for intravenous injection.
Contains ferric carboxymaltose as the active moiety providing 50 mg elemental iron per mL.
Inactive ingredients include water for injection; pH is adjusted with sodium hydroxide or hydrochloric acid to a range of 5.0 to 7.0.
Packaged in single-dose vials of 2 mL (100 mg iron), 15 mL (750 mg iron), and 20 mL (1,000 mg iron) volumes.
Formulated to be stable at room temperature (20°C to 25°C) with excursions allowed between 15°C and 30°C.
Do not freeze the solution; freezing may compromise drug stability and safety.
Colorless to brownish liquid preparation designed for direct intravenous administration as an undiluted slow push or diluted infusion.
Each vial intended for single-use only to prevent contamination and maintain sterility.
Comes with regulatory approval and prescribing information outlining dosing protocols and safety monitoring requirements.
Uses specifically measured elemental iron concentration to enable accurate dosing based on patient weight and clinical need.
Formulated to minimize free iron release and associated adverse oxidative effects.
Packaged in tamper-evident vials to maintain integrity and ensure patient safety.
Available through licensed pharmacies and healthcare providers equipped for parenteral administration.
Produced by American Regent, INC with quality control standards consistent with FDA regulations.
Supplied with detailed storage and handling instructions to preserve physicochemical properties.