Iron Dextran

Class: Iron Preparations
CAS Number: 9004-66-4
Brands: DexFerrum, INFeD

Introduction

Ferric hydroxide¹⁰⁰ or oxyhydroxide¹⁰¹ in a complex with partially hydrolyzed low molecular weight dextran.^{100 101}

Uses for Iron Dextran

Iron Deficiency Not Amenable to Oral Iron Therapy

Treatment of iron deficiency when oral iron preparations are ineffective or cannot be used.^{100 101}

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Iron Dextran Dosage and Administration

General

• Discontinue oral iron therapy prior to initiation of iron dextran therapy.^{100 101} (See Iron, oral under Interactions.)

• Calculate recommended total iron dextran dosage (in mL) for treatment of iron deficiency anemia or iron replacement for blood loss from appropriate dosage formulas; these formulas are not interchangeable.^{100 101} Recommended dosage for treatment of iron deficiency anemia also may be determined from a table; consult manufacturer’s labeling.^{100 101}

• Possible increased incidence of adverse effects, especially delayed reactions, associated with large IV doses of iron dextran, such as those used in total-dose infusions.^{100 101 104}

• Perform periodic determinations of hematologic response (e.g., serum ferritin, blood hemoglobin concentration, hematocrit, and reticulocyte count) during the course of therapy.^{100 101}

Sensitivity Testing

• Administer IV test dose prior to initial and all subsequent therapeutic doses.^{100 101}

• After slow (over 5 minutes) IV injection of 0.5 mL (25 mg of iron), observe for ≥1 hour for sensitivity reactions (see Anaphylaxis under Cautions) before administering the remaining portion of the initial dose.^{100 101}

• Some clinicians recommend administering subsequent routine doses without a test dose if no immediate allergic reactions occur with the initial test dose.¹¹⁷

• Take precautions to treat potential allergic reactions.^{100 101} (See Boxed Warning.)

Administration

Administer undiluted by slow (≤50 mg/minute) IV injection;^{100 101} some preparations (i.e., INFeD) also are FDA-labeled for IM injection.¹⁰⁰ Iron dextran also has been administered diluted by IV infusion† (e.g., over 1–6 hours).^{121 122 123}

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Do not mix with other drugs or add to parenteral nutrition solutions for IV infusion.^{100 101}

Dilution

Dilution not recommended by manufacturers,^{100 101} but there have been reports of total calculated dose of iron dextran being diluted in 250–1000 mL of 0.9% sodium chloride injection for IV infusion†.^{121 122 123}

Use of 5% dextrose injection instead of 0.9% sodium chloride injection may be associated with a higher incidence of local pain and phlebitis.^a

^HID

Rate of Administration

If undiluted, administer by slow IV injection at ≤50 mg/minute (1 mL/minute).^{100 101}

If diluted, administer by IV infusion† over 1–6 hours.^{121 122 123}

IM Administration

Administer by deep IM injection using a 2- or 3-inch, 19- or 20-gauge needle into the upper outer quadrant of the buttock only; alternate buttocks for subsequent injections.¹⁰⁰

If patient is standing, administer IM injection to buttock of the leg opposite the patient’s weight-bearing leg; if supine, place patient in a lateral position with the injection site uppermost.¹⁰⁰

To avoid injection or leakage into subcutaneous tissue, use Z-track injection technique (i.e., firmly pushed aside subcutaneous tissue over the site of injection before inserting the needle).¹⁰⁰

Dosage

Available as iron dextran; dosage expressed in terms of elemental iron.^{100 101} Each mL of iron dextran is equivalent of 50 mg of elemental iron.^{100 101}

Pediatric Patients

Iron Deficiency Anemia

IV or IM

Children weighing 5–15 kg (11–33 lbs): multiply 0.0442 times the patient’s weight in kg (Wt) times the difference between the desired or normal hemoglobin concentration in g/dL (12 g/dL for patients weighing ≤15 kg) and the patient’s observed hemoglobin (Hb_O) concentration in g/dL and then add this value to a factor that accounts for storage iron (0.26 × weight):^{100 101}

[0.0442 × Wt × (12 g/dL - Hb_O)]+ (0.26 × Wt) = total dosage of iron dextran injection in mL

Children weighing >15 kg (33lbs): multiply 0.0442 times the patient’s lean body weight in kg (Wt) times the difference between the desired or normal hemoglobin concentration in g/dL (14.8 g/dL for patients weighing >15 kg) and the patient’s observed hemoglobin (Hb_O) concentration in g/dL and then add this value to a factor that accounts for storage iron (0.26 × lean body weight):^{100 101}

[0.0442 × Wt × (14.8 g/dL - Hb_O)]+ (0.26 × Wt) = total dosage of iron dextran injection in mL

Iron Replacement Secondary to Blood Loss

IV or IM

Use the following formula to calculate required total iron dextran dosage in mL:^{100 101}

0.02 × blood loss (in mL) × hematocrit (expressed as a decimal fraction) = total dosage of iron dextran injection in mL

Adults

Iron Deficiency Anemia

IV or IM

Recommend formula for calculating total dosage in mL of iron dextran injection: multiply 0.0442 times the patient’s lean body weight in kg (Wt) times the difference between the desired or normal hemoglobin (Hb_N) concentration in g/dL (14.8 for adults) and the patient’s observed hemoglobin (Hb_O) concentration in g/dL and then add this value to a factor that accounts for storage iron (0.26 × lean body weight):^{100 101}

[0.0442 × Wt × (14.8 g/dL - Hb_O)]+ (0.26 × Wt) = total dosage of iron dextran injection in mL

Iron Replacement Secondary to Blood Loss

IV or IM

Use the following formula to calculate required total dosage in mL of iron dextran injection containing the equivalent of 50 mg of iron per mL:^{100 101}

0.02 × blood loss (in mL) × hematocrit (expressed as a decimal fraction) = total dosage of iron dextran injection in mL

Prescribing Limits

Pediatric Patients

Iron Deficiency Not Amenable to Oral Iron Therapy

IV or IM

Infants weighing <5 kg (11 lbs): maximum daily dose 25 mg of iron (0.5 mL).^{100 101}

Children weighing 5–9 kg (11–21 lbs): maximum daily dose 50 mg of iron (1 mL).^{100 101}

Children weighing ≥10 kg (22 lbs): maximum daily dose 100 mg of iron (2 mL).^{100 101}

Adults

Iron Deficiency Not Amenable to Oral Iron Therapy

IV or IM

Maximum daily dose 100 mg of iron (2 mL).^{100 101}

Special Populations

Renal Impairment

Iron Deficiency Not Amenable to Oral Iron Therapy

Anemia of Chronic Renal Failure (CRF)

IV

Recommended dosages in adults with anemia of CRF undergoing hemodialysis and receiving epoetin alfa therapy: 50–100 mg of elemental iron given once weekly following an IV test dose of 25 mg.¹¹⁷ Minimum cumulative dose to achieve a favorable hematocrit or hemoglobin response: 1000 mg of elemental iron.¹¹⁷

Once patients achieve transferrin saturation (TSAT) levels ≥20% or serum ferritin concentrations ≥100 ng/mL, continue IV iron therapy at the lowest dose necessary to maintain target hematocrit/hemoglobin levels and iron stores within acceptable limits.¹¹⁷ Weekly maintenance dosage of 25–100 mg of elemental iron for 10 weeks may be appropriate in hemodialysis patients once optimal hematocrit/hemoglobin stores are attained.¹¹⁷ Monitor maintenance iron status by measuring TSAT and serum ferritin concentration every 3 months.¹¹⁷

Withhold iron therapy for up to 3 months if TSAT ≥50% or serum ferritin concentrations ≥800 ng/mL.¹¹⁷ When TSAT decreases to <50% and serum ferritin concentration decreases to <800 ng/mL, IV iron therapy may resumed at one-third to one-half of previous iron dosage.¹¹⁷

Cautions for Iron Dextran

Contraindications

• Anemias not associated with iron deficiency.^{100 101}

• Known hypersensitivity to iron dextran or any ingredient in the formulation.^{100 101}

Warnings/Precautions

Warnings

Anaphylactic-type Reactions

Sensitivity (e.g., anaphylactoid or anaphylactic) reactions, including fatalities, have occurred following parenteral administration of iron dextran.¹⁰¹ (See Anaphylaxis under Cautions.) Such reactions may be immediate or delayed.^{100 101 102 103 104 105 106 107}

Infectious Complications

Possible increased pathogenicity of certain microorganisms;^{110 111 112 113} not recommended for use during the acute phase of infectious renal disease.^{100 101}

Concomitant Cardiac Disorders

Possible exacerbation of cardiovascular complications because of adverse effects of the drug in patients with preexisting cardiovascular disease.^{100 101}

Carcinogenicity

Possible risk of carcinogenesis associated with IM administration of iron-carbohydrate complexes.^{100 101}

Sensitivity Reactions

Anaphylaxis

Manifested as sudden onset of respiratory difficulty (e.g., wheezing, bronchospasm, rigor, dyspnea, cyanosis), tachycardia, hypotension, respiratory arrest, and/or cardiovascular collapse; have resuscitation equipment and personnel trained in detection and treatment of anaphylactic-type reactions readily available during iron dextran administration.^{100 101 102 103 104} (See Boxed Warning.) Administer test dose prior to administration of initial and subsequent therapeutic doses of the drug and observe patient closely.^{100 101} (See Sensitivity Testing under Dosage and Administration.) Fatal reactions have occurred following test dose and also in patients in whom test dose was tolerated.¹⁰¹

Risk for anaphylaxis may be increased in patients with history of drug allergy or multiple drug allergies or with concomitant use of angiotensin-converting enzyme inhibitors.¹⁰¹ Use with caution in patients with a history of clinically important allergies and/or asthma.^{100 101}

General Precautions

Rheumatoid Arthritis

Possible fever and exacerbation or reactivation of joint pain and swelling with IV administration in patients with rheumatoid arthritis; use with extreme caution.^{100 101}

Misuse

Excess storage of iron and a syndrome similar to hemosiderosis possible when used for anemia not attributable to iron deficiency (e.g., those with hemoglobinopathies and other refractory anemias that might be erroneously diagnosed as iron deficiency anemias).^{100 101}

Specific Populations

Pregnancy

Category C.^{100 101}

Lactation

Distributed into milk (as traces of unmetabolized iron dextran); use with caution in nursing women.^{100 101}

Pediatric Use

Possible increased incidence of gram-negative sepsis; not recommended for use in infants <4 months of age.^{100 101}

Hepatic Impairment

Use with extreme caution in patients with serious impairment of hepatic function.¹⁰⁰

Renal Impairment

Systemic exposure to iron dextran may be increased.^a (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Sensitivity (e.g., anaphylactoid or anaphylactic) reactions; can be immediate or delayed and vary widely in severity.^{100 101 102 103 104 105 106 107}

Interactions for Iron Dextran

Specific Drugs and Laboratory Test Interactions

Drug or Test	Interaction	Comment
Angiotensin converting-enzyme inhibitors101	May increase risk for anaphylaxis with concomitant use101
Bone scans using imaging agents labeled with technetium Tc 99m (diphosphonate)101	Dense, cresentic areas of activity along the contour of the iliac crest, visualized 1–6 days after IM administration of iron dextran100 101 Possible reduced bone uptake, marked renal activity, and excessive blood pool and soft tissue accumulation100 101
Iron, oral	Therapeutic duplication; increased risk for iron toxicity100 101	Concomitant use not recommended100 101
Test for anemia	Serum iron determinations (especially colorimetric assays) may not be meaningful for 3 weeks following the administration of iron dextran100 101 Serum ferritin concentrations peak approximately 7–9 days following an IV iron dextran dose and slowly return to baseline over a period of about 3 weeks100 Bone marrow examination for iron stores may not be meaningful for prolonged periods following iron dextran therapy because residual iron dextran may remain in the reticuloendothelial cells100 101	Interpret test results with caution100
Test for blood chemistry	May cause falsely elevated values of serum bilirubin and falsely decreased values of serum calcium100 101
Test for coagulation	Prolonged partial thromboplastin time following IV administration of iron dextran when the blood sample for the test is mixed with anticoagulant citrate dextrose solution but not sodium citrate solutiona Blood typing and cross-matching unaffecteda

Iron Dextran Pharmacokinetics

Absorption

Bioavailability

Absorbed slowly from the site of IM injection, principally through the lymphatic system;^a 60% of an IM dose after 3 days, up to 90% after 1–3 weeks; and the remainder gradually absorbed over a period of several months or longer.^a

Absorbed very slowly from subcutaneous tissue; stains skin for up to 2 years if the drug is deposited in this tissue.^a

Onset

In iron-deficient patients, reticulocytosis may begin by the 4th day following an IV infusion of the total calculated dose of iron dextran and reaches a maximum by about the 10th day.^a

Distribution

Extent

After reticuloendothelial cells separate iron from the iron dextran complex, iron becomes a part of the body’s total iron stores.¹²¹

Crosses the placenta and small amounts of iron apparently reach the fetus.¹⁰⁰

Distributed into breast milk, but only as trace amounts of unmetabolized iron dextran.¹⁰⁰

Elimination

Elimination of iron from serum, including elimination half-life, does not correspond to clearance of the mineral from the body.^{100 101}

Elimination Route

Excreted in urine, bile, or feces, but only as trace amounts of unmetabolized iron dextran.^a

Half-life

In doses ≤500 mg, iron dextran plasma concentrations decrease exponentially with a half-life of about 6 hours.^a

Special Populations

In iron-deficient patients with coexistent end-stage renal disease and other clinical problems, the serum elimination half-life of iron averaged 58.9 hours (range: 9.4–87.4 hours) following IV administration of iron dextran.¹⁰¹

Negligibly removed by hemodialysis.^{101 115 116}

Stability

Storage

Parenteral

Injection

20–25°C; excursions permitted to 15–30°C.^{100 101}

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Dextrose 5%
Sodium chloride 0.9%

Actions

• Corrects the erythropoietic abnormalities that are due to a deficiency of iron.^a

• Does not stimulate erythropoiesis nor does it correct hemoglobin disturbances not caused by iron deficiency.^a

Advice to Patients

• Risk of anaphylactic reactions.^{100 101}

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{100 101}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.^{100 101}

• Importance of informing patients of other important precautionary information.^{100 101} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Iron Dextran

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV use	equivalent to iron 50 mg/mL	DexFerrum	American Regent
	Injection, for IV or IM use	equivalent to iron 50 mg/mL	INFeD	Watson