Iron Sucrose

Introduction Overview

Generic Name

iron sucrose

Brand Name

Venofer

Dosage Form

Injection (intravenous infusion)

Drug Class

Iron products

Pharmacokinetics

Absorption:
Iron sucrose is administered intravenously, bypassing the gastrointestinal tract, hence absorption via oral or enteral routes is not applicable. Unlike oral iron formulations, iron sucrose infusions provide direct delivery of iron into systemic circulation, allowing for rapid availability to tissues. The bioavailability is effectively 100% as the drug is injected directly into the bloodstream. This route avoids absorption variability commonly encountered with oral iron, such as interference from dietary factors or gastrointestinal pathology.

Distribution:
Following intravenous administration, iron sucrose dissociates and releases iron, which binds predominantly to transferrin in plasma for transport. The iron distributes primarily to the liver, spleen, bone marrow, and other reticuloendothelial system organs. Iron is taken up by developing erythrocytes in the bone marrow for hemoglobin synthesis. The extent of distribution depends on the iron status of the patient and ongoing erythropoiesis. Studies have demonstrated that the administered iron is quickly utilized for hemoglobin production or stored as ferritin in macrophages, with minimal free iron remaining in plasma.

Metabolism:
Iron sucrose complex undergoes breakdown in the reticuloendothelial system. The sucrose moiety is hydrolyzed and cleared, while the released iron enters normal iron metabolic pathways. Iron is incorporated into ferritin or hemosiderin for storage, or transported as transferrin-bound iron for erythropoiesis. Since iron is an endogenous metal, it is not metabolized in the classical sense but recycled through physiological iron homeostasis mechanisms involving macrophage recycling and storage.

Elimination:
Excretion of iron from the body is highly regulated and minimal, occurring primarily via sloughing of intestinal mucosal cells, sweat, urine, and menstrual blood loss rather than renal or hepatic clearance of the administered drug. Excess iron can accumulate in tissues if dosing is excessive. The sucrose component is eliminated via renal excretion. The terminal half-life of iron sucrose complexes is variable depending on iron requirements and mobilization, but generally approximately 6-12 hours. Repeated infusions require close monitoring to prevent iron overload and toxicity.

Dosage Forms

Available Dosage Forms:
- Intravenous injection or infusion vial containing iron sucrose equivalent to 20 mg/mL elemental iron.
- Venofer typically supplied as 5 mL (100 mg iron) or 10 mL (200 mg iron) single-dose vials for IV use.

Dosages for Adults and Adolescents:
- Recommended doses usually range from 100 mg to 200 mg of elemental iron administered intravenously per session.
- The frequency and total dose depend on the severity of iron deficiency anemia and patient iron requirements.
- Infusion durations often vary, with a slow infusion lasting up to 2.5 hours to minimize adverse reactions.
- Treatment courses involve multiple infusions, with cumulative doses tailored based on laboratory monitoring of hemoglobin and ferritin.

Specific Patient Populations:
- For patients with chronic kidney disease undergoing hemodialysis, IV iron sucrose is often administered during dialysis sessions to manage anemia.
- Pediatric dosing (for children aged 2 years and older) is adjusted based on body weight and iron deficit calculations.
- Use in pregnancy requires careful risk-benefit assessment due to potential fetal risks from severe maternal reactions versus benefits of correcting maternal anemia.
- Dosage adjustments are necessary in patients with impaired renal function or previous hypersensitivity to iron compounds.

Clinical guidelines emphasize individualized dosing strategies with close monitoring of iron status markers to optimize efficacy and safety.

Mechanism Of Action

Iron sucrose functions as an injectable iron preparation intended to replenish iron stores in the body, primarily used to treat iron deficiency anemia. Upon intravenous administration, the iron sucrose complex dissociates, releasing bioavailable elemental iron. This iron binds to transferrin, a plasma protein responsible for iron transport, which delivers iron to erythroid precursor cells in the bone marrow, facilitating hemoglobin synthesis and restoration of normal red blood cell production.

The molecular mechanism involves the direct supplementation of iron required for critical cellular functions such as oxygen transport and enzymatic reactions. Iron is a central component of hemoglobin, myoglobin, and various cytochromes. By replenishing iron, iron sucrose corrects the deficit impeding erythropoiesis, alleviating symptoms of anemia.

Cellular uptake of iron delivered by iron sucrose involves receptor-mediated endocytosis of transferrin-bound iron into developing erythrocytes. Simultaneously, iron is stored in macrophages as ferritin or hemosiderin, maintaining iron homeostasis and preventing free radical formation. This balance reduces oxidative stress compared to free iron forms.

Compared with other intravenous iron formulations, iron sucrose has a relatively low molecular weight complex which allows controlled release of iron and a favorable safety profile. Clinical studies demonstrate that iron sucrose achieves effective hemoglobin improvement with fewer severe hypersensitivity reactions compared to iron dextran. Its mechanism ensures prompt correction of anemia in patients who cannot tolerate or absorb oral iron, such as those with chronic kidney disease or chemotherapy-induced anemia.

Pharmacological Actions

Replenishes depleted iron stores by providing bioavailable elemental iron.
Facilitates hemoglobin synthesis by supplying iron necessary for erythropoiesis.
Enhances oxygen transport capacity by correcting iron deficiency anemia.
Supports energy metabolism through restoration of iron-dependent enzymatic functions.
Bypasses gastrointestinal absorption limitations by delivering iron intravenously.
Provides controlled release of iron with reduced risk of free iron toxicity.
Reduces the need for blood transfusions in patients with chronic kidney disease.
Exerts a favorable safety profile with minimized immunogenicity compared to other parenteral iron complexes.
Improves quality of life and functional status in anemic patients.
Modulates inflammatory states by correcting iron deficiency that exacerbates chronic disease.
Potentially decreases erythropoiesis-stimulating agent requirements in dialysis patients.
Quickly restores iron for immediate utilization in active marrow cells.
Minimizes gastrointestinal side effects commonly associated with oral iron therapy.

Therapeutic Or Clinical Uses

Treatment of iron deficiency anemia in adults and children aged 2 years and older.
Management of anemia associated with chronic kidney disease, including those on hemodialysis.
Correction of iron deficiency due to chemotherapy-induced anemia.
Treatment of iron deficiency anemia when oral iron therapy is ineffective or not tolerated.
Used to replenish iron stores prior to erythropoiesis-stimulating agent therapy.
Management of iron deficiency in patients with malabsorption syndromes or gastrointestinal disorders.
Treatment option for patients with significant blood loss requiring rapid iron repletion.
Adjunct therapy to improve hemoglobin levels and reduce transfusion requirements in anemia of chronic disease.
Supportive treatment in pregnant women with documented iron deficiency anemia where oral therapy is inadequate.
Therapy for iron deficiency anemia in surgical patients with preoperative anemia.
Use in patients with inflammatory bowel disease experiencing active iron deficiency anemia.
Treatment for anemic patients with intolerance to oral iron formulations due to gastrointestinal side effects.
Management of iron deficiency during chronic inflammatory conditions limiting oral iron absorption.

Side Or Adverse Effects

Hypersensitivity reactions including rash, itching, hives, and anaphylaxis in rare cases.
Injection site irritation, pain, swelling, or bruising.
Transient elevation or fluctuation of blood pressure including episodes of hypotension or hypertension.
Flu-like symptoms such as fever, chills, and malaise.
Nausea, vomiting, diarrhea, or abdominal discomfort following infusion.
Headache and dizziness occurring during or shortly after administration.
Muscle cramps, joint or back pain reported in some patients.
Signs of inflammation in the gastrointestinal tract including abdominal pain and bloating.
Risk of iron overload leading to tissue deposition if dosed improperly.
Potential for alterations in liver function tests.
Possible development of hypophosphatemia with prolonged therapy.
Rare cases of vascular access complications in patients on hemodialysis.
Allergic reactions including swelling of face, lips, tongue, or throat requiring emergency intervention.
Fatigue or weakness as a nonspecific adverse event during treatment.
Transient changes in taste or metallic taste during infusion.

Precautions

Screen patients for known hypersensitivity to parenteral iron before administration.
Monitor for signs of iron overload, especially in patients receiving repeated doses.
Use caution in patients with hemochromatosis or other iron storage disorders.
Observe closely for hypersensitivity reactions during and after administration, with at least 30 minutes of post-infusion monitoring.
Inform patients to report any signs of allergic reactions immediately.
Avoid rapid infusion to minimize risk of hypotension and adverse events.
Evaluate iron status with laboratory tests such as serum ferritin and transferrin saturation prior to and during therapy.
Use caution in pregnant women; balance maternal benefits against potential fetal risks.
Monitor blood pressure as transient hypertension or hypotension may occur.
Adjust doses carefully in patients with chronic kidney disease and those on dialysis.
Avoid concurrent use with oral iron supplements as it may reduce absorption.
Educate patients about symptoms of potential adverse effects, including gastrointestinal disturbances and injection site reactions.
Use with caution in patients with active infections or inflammatory conditions.
Ensure adequate resuscitation equipment and trained personnel are available during administration.
Consider alternative therapies in patients with a history of anaphylaxis to intravenous iron.

Warnings

Contraindicated in patients with known allergic reactions to iron sucrose or other parenteral iron products.
Do not administer to patients with iron overload or diseases such as hemochromatosis.
Risk of severe hypersensitivity reactions including anaphylaxis; emergency measures should be ready.
May impair absorption of oral iron preparations, impacting concurrent oral iron therapy.
Use caution in patients with unstable or uncontrolled hypertension due to potential blood pressure fluctuations.
Pregnancy: potential risk to fetus if severe hypersensitivity occurs; weigh risk versus benefit.
Monitor closely in patients with previous multiple blood transfusions or iron therapy to avoid iron overload.
Infusion-related reactions may occur, including burning sensation or pain at infusion site.
Not to be used for anemia not caused by iron deficiency.
Avoid rapid bolus injections to prevent adverse cardiovascular effects.
Should only be given by healthcare professionals trained in intravenous administration and management of anaphylaxis.
Patients should be observed for at least 30 minutes post-infusion for adverse events.
Use with caution in patients with hypertension or cardiovascular disease due to blood pressure effects.
Discontinue therapy in case of signs of serious hypersensitivity or intolerance.
Avoid use in pediatric patients under 2 years due to safety data limitations.

Contraindication

Hypersensitivity or allergy to iron sucrose or any component of the formulation.
Known iron overload states such as hemochromatosis and hemosiderosis.
Anemia not caused by iron deficiency (e.g., hemolytic anemia, anemia of chronic disease without iron deficiency).
Patients with acute infections where iron supplementation may exacerbate infection.
Severe asthma or other hypersensitive conditions exacerbated by intravenous iron preparations.
Patients with evidence of pre-existing severe allergic reactions to parenteral iron therapy.
Use contraindicated in patients with iron storage disorders leading to excess body iron.
Contraindicated in patients with active liver diseases related to iron metabolism abnormalities.
Patients with known hypersensitivity reactions to intravenous iron dextran or similar compounds may be contraindicated pending further evaluation.
Not recommended for use in children under 2 years of age due to limited safety data.

Drug Interactions

Concurrent oral iron supplements such as ferrous sulfate, ferrous fumarate, or ferrous gluconate may have reduced absorption due to intravenous iron therapy.
Iron sucrose may decrease the effectiveness of oral iron formulations by impairing gastrointestinal absorption.
Potential interaction with certain antibiotics like tetracyclines and quinolones which may form insoluble complexes with iron.
May interfere with absorption of levothyroxine resulting in decreased thyroid hormone levels.
Concomitant use with methyldopa may affect blood pressure control.
Iron can interact with certain antacids, decreasing iron bioavailability when co-administered orally, but this is less significant with IV iron.
Possible interference with diagnostic tests including serum iron, total iron-binding capacity, and ferritin levels following administration.
Co-administration with erythropoiesis-stimulating agents may increase hematologic response requiring dose adjustments.
Iron sucrose may alter plasma levels of medications metabolized by hepcidin-regulated pathways.
Vitamin C may enhance iron uptake when used concomitantly, but clinical significance during IV use is minimal.
Herbal supplements containing iron or vitamin C may augment iron levels, necessitating monitoring to avoid overload.
Use with caution when combined with other intravenous iron dextran formulations to prevent iron overload.
Possible additive hypotensive effects when combined with antihypertensive agents during infusion.
No significant interactions reported with common analgesics or anti-inflammatory drugs.
Patients should provide a full medication list to healthcare providers prior to iron sucrose treatment.

Preparations Of The Drug

Venofer is supplied as a sterile aqueous solution of iron sucrose for intravenous use.
Available in single-dose vials containing 100 mg or 200 mg elemental iron per vial.
Solutions are typically clear, dark brown to black in color reflecting iron content.
Packaged in 5 mL (100 mg) and 10 mL (200 mg) glass vials requiring dilution prior to slow infusion.
Prepared under aseptic technique by trained healthcare personnel before administration.
Should be diluted appropriately according to prescribing information to reduce risk of adverse reactions.
Stored at controlled room temperature, protected from light.
Discard any unused portion after single use to avoid contamination.
Packaging includes detailed labeling with indications, dosing instructions, and warnings.
Additional iron sucrose preparations are marketed under generic names in various countries.
Typically supplied with accompanying administration sets suitable for intravenous infusion.
Stability is maintained as a complex between iron and sucrose moieties ensuring controlled release.
Not intended for intramuscular or subcutaneous routes due to risk of tissue damage.
Vials are generally designed for single patient use to minimize infection risk.
Instructions for proper disposal of unused medication and sharps are included in product literature.