Iron Dextran

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

Warning(s)

  • Risk of developing potentially life-threatening anaphylactic reactions.100 101 119 (See Anaphylaxis under Cautions.) Patients with a history of drug allergy or multiple drug allergies may be at increased risk of anaphylactic-type reactions to iron dextran.101 119 120

    Use only in patients in whom a clearly established indication for parenteral iron therapy exists, confirmed by appropriate clinical and laboratory tests.100 101 119

  • Should be administered by qualified individuals117 with ready access to resuscitation equipment and appropriate agents for the treatment of a severe allergic or anaphylactic reaction (e.g., epinephrine, or isoproterenol in patients receiving β-adrenergic blocking agents).100 101 102 103 104 117 119 120

  • Administer test dose prior to first therapeutic dose.101 119 120

  • During administration of any iron dextran dose, observe for manifestations of anaphylactic-type reactions.101 119 120 Fatal reactions have occurred following a test dose of iron dextran and also in patients in whom the test dose was tolerated.101 119 120

  • If no manifestations of anaphylactic-type reactions occur after test dose, administer full therapeutic dose.101 119

Introduction

Ferric hydroxide100 or ferric 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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In patients with chronic kidney disease (CKD) on hemodialysis, IV iron superior to orally administered iron for increasing hemoglobin concentrations and/or minimizing dosage of an erythropoiesis-stimulating agent (ESA); the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guidelines state that the IV route is preferred for iron administration in such patients.117

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 for treatment of iron deficiency anemia or iron replacement for blood loss from appropriate dosage formulas; these formulas are specific for each indication and 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 test dose by intended route of administration for therapeutic doses prior to initial therapeutic dose.100 101

  • After slow IV injection (given over ≥30 seconds for INFeD or ≥5 minutes for Dexferrum) or IM injection (INFeD) of 25 mg of iron (0.5 mL), observe for ≥1 hour for sensitivity reactions (see Anaphylaxis under Cautions) before administering the remaining portion of the initial dose.100 101

  • Take precautions to be prepared 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 after dilution 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 the 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

INFeD preparation: 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.100

If patient is standing, administer IM injection in 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 push 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 injection 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): Use the following formula (where Wt = patient's weight in kg and Hbo = observed hemoglobin in g/dL):100 101

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

Children weighing >15 kg (33 lbs): Use the following formula (where Wt = patient's weight in kg and Hbo = observed hemoglobin in g/dL):100 101

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

Adults

Iron Deficiency Anemia
IV or IM

Recommended formula (where Wt = patient's weight in kg and Hbo = observed hemoglobin in g/dL) for calculating total dosage of iron dextran injection (in mL):100 101

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

Iron Replacement Secondary to Blood Loss
IV or IM

Use the following formula to calculate required total dosage of iron dextran injection (in mL):100 101

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

Prescribing Limits

Pediatric Patients

Iron Deficiency Not Amenable to Oral Iron Therapy
IV or IM

Infants weighing <5 kg (11 lbs): Maximum daily dosage is 25 mg of iron.100 101

Children weighing 5–9 kg (11–21 lbs): Maximum daily dosage is 50 mg of iron.100 101

Children weighing ≥10 kg (22 lbs): Maximum daily dosage is 100 mg of iron.100 101

Adults

Iron Deficiency Not Amenable to Oral Iron Therapy
IV or IM

Maximum daily dosage is 100 mg of iron.100 101

Special Populations

Renal Impairment

Iron Deficiency Not Amenable to Oral Iron Therapy
Anemia of Chronic Kidney Disease (CKD)
IV

In patients with CKD receiving an ESA, administer sufficient iron to maintain selected targets of iron therapy (i.e., transferrin saturation and serum ferritin concentrations); periodically monitor these iron indices and use results (in conjunction with hemoglobin concentrations and ESA dosage) to guide iron therapy.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 ACE inhibitors.101 Risk for anaphylactic-type reactions to specific iron dextran preparations is not known and may vary.100 101 Use with caution in patients with a history of clinically important allergies and/or asthma.100 101

Iron dextran preparations differ in chemical characteristics and may differ in clinical effects; manufacturers state that such preparations are not clinically interchangeable.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

ACE inhibitors101

May increase risk for anaphylaxis with concomitant use101

Bone scans using imaging agents labeled with technetium Tc 99m (diphosphonate)101

Dense, crescentic 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 CompatibilityHID

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 50 mg of elemental iron per mL

Dexferrum

American Regent

Injection, for IV or IM use

equivalent to 50 mg of elemental iron per mL

INFeD

Watson

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 4, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Watson Pharmaceuticals. INFeD (iron dextran injection, USP) prescribing information. Corona, CA; 2009 Sept.

101. American Regent Laboratories, Inc. Dexferrum (iron dextran injection, USP) prescribing information. Shirley, NY; 2008 Aug.

102. Fishbane S, Ungureanu VD, Maesaka JK et al. The safety of intravenous iron dextran in hemodialysis patients. Am J Kidney Dis. 1996; 28:1529-34.

103. Auerbach M, Witt D, Toler W et al. Clinical use of the total dose intravenous infusion of iron dextran. J Lab Clin Med. 1988; 111:566-70. [IDIS 241017] [PubMed 3361236]

104. Hamatra RD, Block MH, Schocket AL. Intravenous iron dextran in clinical medicine. JAMA. 1980; 243:1726-31. [IDIS 124186] [PubMed 6154155]

105. Shimada A. Adverse reactions to total-dose infusion of iron dextran. Clin Pharm. 1982; 1:248-9. [IDIS 150350] [PubMed 7185520]

106. Becker CE, MacGregor RR, Walker KS et al. Fatal anaphylaxis after intramuscular iron-dextran. Ann Intern Med. 1966; 65:745-8. [PubMed 5926393]

107. Zipf RE Jr. Fatal anaphylaxis after intravenous iron dextran. J Forensic Sci. 1975; 20:326-33. [PubMed 1123602]

108. Novey HS, Pahl M, Haydik I et al. Immunologic studies of anaphylaxis to iron dextran in patients on renal dialysis. Ann Allergy. 1994; 72:224-8. [PubMed 7510461]

109. Lloyd KN, Williams P. Reactions to total dose infusion of iron dextran in rheumatoid arthritis. Br Med J. 1970; 1:323-5.

110. Jurado RL. Iron, infections, and anemia of inflammation. Clin Infect Dis. 1997; 25:888-95. [PubMed 9356804]

111. Jacobus DP. Randomization to iron supplementation of patients with advanced human immunodeficiency virus disease—an inadvertent but controlled study with results important for patient care. J Infect Dis. 1996; 173:1044-5. [IDIS 362109] [PubMed 8603950]

112. Vildé JL, Salmon-Céron D. Randomization to iron supplementation of patients with advanced human immunodeficiency virus disease—an inadvertent but controlled study with results important for patient care. J Infect Dis. 1996; 173:1045. [PubMed 8603951]

113. Weinberg GA. Iron and oxidative stress as a mechanism for the enhanced production of human immunodeficiency virus by alveolar macrophages from otherwise healthy cigarette smokers. J Clin Infect Dis. 1996; 173:1045-6.

114. Friel JK, Andrews WL, Hall MS et al. Intravenous iron administration to very-low-birth-weight newborns receiving total and partial parenteral nutrition. J Parenter Enteral Nutr. 1995; 19:114-8.

115. Hatton RC, Portales IT, Finley A et al. Removal of iron dextran by hemodialysis: an in vivo study. Am J Kidney Dis. 1995; 26:327-330. [PubMed 7645537]

116. Manuel MA, Stewart WK, St. Clair Neill GD et al. Loss of iron-dextran through cuprophane membrane of disposable coil dialyser. Nephron. 1972; 9:94-8. [PubMed 4634565]

117. National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis. 2006; 47(suppl 3):S1-S146.

118. Nissenson AR. Achieving target hematocrit in dialysis patients: new concepts in iron management. Am J Kidney Dis. 1997; 30(6):907-11. [IDIS 398274] [PubMed 9398140]

119. Bregman D. Dear healthcare professional letter: Important drug warning for Dexferrum (iron dextran injection, USP). Shirley, NY: American Regent; 2009 Sep 25.

120. Food and Drug Administration. Dexferrum (iron dextran) injection [October 16, 2009: American Regent]. MedWatch drug labeling changes. Rockville, MD. From FDA website (http: / / www.fda.gov / Safety / MedWatch / SafetyInformation / SafetyAlertsforHumanMedicalProducts / ucm186899.htm).

121. Koutroubakis IE, Oustarnanolakis P, Karakoidas C et al. Safet and efficacy of total-dose infusion of low molecular weight iron dextran for iron deficiency anemia in patients with inflammatory bowel disease. Dis Dis Sci. 2010; 55:2327-31.

122. Lew I, Mullarkey T, Adamson RT et al. Integrated care of anemia in chronic kidney disease patients. concepts in intravenous iron management: part one. Hosp Pharm. 2010; 45:225-36.

123. Reddy CM, Kathula SK, Ali SA et al. Safety and efficacy of total dose infusion of iron dextran in iron deficiency anaemia. Int J Clin Pract. 2008; 62:413-5. [PubMed 18005041]

a. AHFS drug information 2004. McEvoy GK , ed. Iron dextran. Bethesda, MD: American Society of Health-System Pharmacists; 2007:961-2.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:961-2.

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