Iron Dextran Complex

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Infed: 50 mg/mL (2 mL)

Pharmacology

Mechanism of Action

The released iron, from the plasma, eventually replenishes the depleted iron stores in the bone marrow where it is incorporated into hemoglobin

Pharmacokinetics/Pharmacodynamics

Absorption

IM: 60% absorbed after 3 days; 90% after 1 to 3 weeks, the balance is slowly absorbed over months

IV: Uptake of iron by the reticuloendothelial system appears to be constant at about 10 to 20 mg/hour

Excretion

Urine and feces via reticuloendothelial system

Onset of Action

Hematologic response to either oral or parenteral iron salts is essentially the same; red blood cell form and color changes within 3 to 10 days

Maximum effect: Peak reticulocytosis occurs in 5 to 10 days, and hemoglobin values increase within 2 to 4 weeks; serum ferritin peak: 7 to 9 days after IV dose

Half-Life Elimination

48 hours

Use: Labeled Indications

Iron deficiency: Treatment of iron deficiency in patients in whom oral administration is unsatisfactory or infeasible

Contraindications

Hypersensitivity to iron dextran or any component of the formulation; any anemia not associated with iron deficiency

Dosage and Administration

Dosing: Adult

Note: A 25 mg test dose should be administered prior to starting iron dextran therapy; observe for at least 1 hour (after test dose) prior to administering the therapeutic dose. Discontinue oral iron products prior to administering iron dextran.

Iron-deficiency anemia: IM (INFeD, DexIron [Canadian product]), IV (INFeD, DexIron [Canadian product]):

Total dose (mL) = 0.0442 (desired hemoglobin - observed hemoglobin) x LBW + (0.26 x LBW)

Desired hemoglobin: Usually 14.8 g/dL

LBW = Lean body weight in kg

Total dose infusion (off label): Data from a retrospective analysis suggest that a total dose infusion of iron dextran 1,000 mg over 1 hour is safe and effective in patients with iron deficiency anemia; in patients who had not previously received IV iron, a test dose of ~40 mg was administered over 5 minutes, followed by observation (for 15 minutes), and then the balance of the dose (Auerbach 2011).

Iron replacement therapy for blood loss: IM (INFeD, DexIron [Canadian product]), IV (INFeD, DexIron [Canadian product]): Replacement iron (mg) = blood loss (mL) x Hct

Maximum daily dosage (manufacturer's labeling): Replacement of larger estimated iron deficits (total dose) may be achieved by serial administration of smaller incremental daily doses. Daily dosages should usually be limited to 100 mg iron (2 mL).

Cancer-/chemotherapy-associated anemia: IV: Note: Use the iron-deficiency anemia equation for determining a calculated dose, when applicable.

Weekly administration (off-label dosing; INFeD [Auerbach 2004]):

Weeks 1 to 3: Test dose of 25 mg (over 1 to 2 minutes), followed by 75 mg (bolus) once weekly

Weeks 4 and after: 100 mg over 5 minutes once weekly until the calculated dose is reached

Total dose infusion (off-label dosing; INFeD): Test dose of 25 mg (over 1 to 2 minutes), followed 1 hour later by the balance of the calculated total dose mixed in 500 mL NS and infused at 175 mL/hour (Auerbach 2004)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Multiple forms for parenteral iron exist; close attention must be paid to the specific product when ordering and administering; incorrect selection or substitution of one salt form for another (dextran vs sucrose) without proper dosage adjustment may result in serious over- or underdosing; test doses are recommended before starting therapy. Discontinue oral iron products prior to administering iron dextran. Dosing presented as both mg and mL; use caution when ordering and dispensing.

Note: Iron dextran: 1 mL provides 50 mg elemental iron.

Iron deficiency anemia: Infants ≥4 months, Children, and Adolescents: IM, IV:

Test dose: Usual reported range: 10 to 25 mg (0.2 to 0.5 mL) administered 1 hour prior to starting iron dextran therapy (Ruiz-Jaramillo 2004; Warady 2004). The manufacturer suggests a fixed test dose of 25 mg (0.5 mL); however, lower doses and a weight-based approach may be preferable and some centers have used the following (Gura 2011):

Infants ≥4 months and <10 kg: 10 mg (0.2 mL).

Children 10 to 20 kg: 15 mg (0.3 mL).

Children >20 kg and Adolescents: 25 mg (0.5 mL).

Calculating total replacement dosage of iron dextran:

Dose (mL) = 0.0442 (Hb_n - Hb_o) x LBW + (0.26 x LBW).

LBW = lean body weight in kg. Note: For patients weighing 5 to 15 kg, use actual body weight.

Hb_n = desired hemoglobin (g/dL) = 12 g/dL if ≤15 kg or 14.8 g/dL if >15 kg.

Hb_o = measured hemoglobin (g/dL).

Intermittent dosing for replacement (multiple doses): Calculate total volume of dose (iron dextran 50 mg/mL elemental iron) from previous equation; if total replacement dose is large, may consider dividing total dose and utilizing smaller incremental dosages not to exceed recommended maximum daily dosages for route.

Usual maximum daily dosage:

IV: 100 mg (2 mL)/day.

IM:

Infants ≥4 months and <5 kg: 25 mg (0.5 mL)/day.

Infants ≥4 months and Children 5 to 10 kg: 50 mg (1 mL)/day.

Children >10 kg and Adolescents: 100 mg (2 mL)/day.

Total dose infusion: Limited data available; optimal regimen not defined: Infants ≥11 months, Children, and Adolescents: Calculate total dose based on previous equation (total dose should not to exceed 1,000 mg/dose) and administer as a single infusion over 1 hour. Dosing based on experience reported in an observational case series of patients in an outpatient hematology clinic with iron deficiency anemia who were not candidates for oral therapy (n=31; ages: 11 months to 18 years); patients were first administered a test dose of 30 mg over 5 minutes; if no reaction after 15 minutes of observation, the total replacement dose (not to exceed 1,000 mg) was administered; adverse reactions were observed and reported as mild and transient; 5 patients discontinued therapy due to adverse reactions (Plummer 2013). A retrospective study of pediatric and young adult patients with inflammatory bowel disease (n=34; ages: 6.2 to 20.8 years) reported a similar total dose replacement approach; a test dose of 25 mg was reported and a maximum dose of 2,000 mg over 2 hours was used; 11 allergic reactions were reported; 10 of them were observed during the test dose (Mamula 2002).

Acute blood loss; iron replacement: Note: Assumption: 1 mL of normocytic, normochromic red cells = 1 mg elemental iron; Calculate total volume of dose (iron dextran 50 mg/mL elemental iron); if total replacement dose is large, may consider dividing total dose and utilizing smaller incremental dosages not to exceed recommended maximum daily dosages for route.

Infants ≥4 months, Children, and Adolescents: IM, IV:

Replacement iron (mg) = Blood loss (mL) x hematocrit (expressed as a decimal fraction).

Usual maximum daily dosage:

IV: 100 mg (2 mL)/day.

IM:

Infants ≥4 months <5 kg: 25 mg (0.5 mL)/day.

Children 5 to 10 kg: 50 mg (1 mL)/day.

Children >10 kg and Adolescents: 100 mg (2 mL)/day.

Anemia of chronic renal failure: Note: Initiation of iron therapy, determination of dose, and duration of therapy should be guided by results of iron status tests combined with the Hb level and the dose of the erythropoietin stimulating agent. See Reference Range for target levels. There is insufficient evidence to recommend IV iron if ferritin level >500 ng/mL (KDOQI 2006).

Dosing based on the 2000 KDOQI Anemia Guidelines (KDOQI 2001). More recent KDOQI guidelines and the KDIGO guidelines no longer provide specific dosing recommendations or preferred product for intravenous iron supplementation (KDOQI 2006; KDIGO 2012).

Predialysis or peritoneal dialysis: Infants and Children: As a single dose repeated as often as clinically indicated: IV:

<10 kg: 125 mg.

10 to 20 kg: 250 mg.

>20 kg: 500 mg.

Hemodialysis: Infants, Children, and Adolescents: Administer during each dialysis for 10 doses total: IV:

<10 kg: 25 mg.

10 to 20 kg: 50 mg.

>20 kg: 100 mg.

Reconstitution

Solutions for infusion should be diluted in 250 to 1,000 mL NS.

Total dose infusion (off-label dose): Dilute in 250 or 500 mL NS; refer to protocol for details (Auerbach 2004; Auerbach 2011).

Administration

Note: A test dose should be administered on the first day of therapy; administer slowly over at least 30 seconds and observe for at least 1 hour for hypersensitivity reaction, then administer the remainder of the day's therapeutic dose (dose minus test dose). Resuscitation equipment, medication, and trained personnel should be available. An uneventful test dose does not ensure an anaphylactic-type reaction will not occur during administration of the therapeutic dose.

IM (INFeD, DexIron [Canadian product]): Use Z-track technique (displacement of the skin laterally prior to injection); injection should be deep into the upper outer quadrant of buttock; alternate buttocks with subsequent injections. Administer test dose at same recommended site using the same technique.

IV: Test dose should be administered gradually over at least 30 seconds (INFeD) or 5 minutes (DexIron [Canadian product]), or over 1 to 2 minutes (INFeD) for cancer-/chemotherapy-associated anemia (Auerbach 2004). Subsequent dose(s) may be administered undiluted at a slow gradual rate not to exceed 50 mg/minute (maximum: 100 mg).

Avoid dilutions with dextrose (increased incidence of local pain and phlebitis).

Total dose infusion (off-label administration): A retrospective analysis in patients with iron deficiency anemia suggests that a total dose infusion of 1,000 mg (diluted in 250 mL of NS) over 1 hour (after an initial test dose) is safe and effective (Auerbach 2011). Another retrospective analysis in patients with chronic kidney disease and iron deficiency anemia administered the total dose (after the initial test dose) over 4 to 6 hours (Dossabhoy 2014). Total dose infusions may be associated with an increased incidence of adverse effects 24 to 48 hours after the infusion. In patients with cancer-/chemotherapy-associated anemia, 1 hour after the test dose, administer the balance of the dose diluted in 500 mL NS and infuse at 175 mL/hour (Auerbach 2004).

Storage

Store intact vials at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Management: Follow iron dextran recommendations closely regarding both having resuscitation equipment and trained personnel on-hand prior to iron dextran administration and the use of a test dose prior to the first therapeutic dose. Consider therapy modification

Dimercaprol: May enhance the nephrotoxic effect of Iron Preparations. Avoid combination

Test Interactions

May cause falsely elevated values of serum bilirubin and falsely decreased values of serum calcium. Residual iron dextran may remain in reticuloendothelial cells; may affect accuracy of examination of bone marrow iron stores. Bone scans with 99m Tc-labeled bone seeking agents may show reduced bony uptake, marked renal activity, and excess blood pooling and soft tissue accumulation following IV iron dextran infusion or with high serum ferritin levels. Following IM iron dextran, bone scans with 99m Tc-diphosphonate may show dense activity in the buttocks.

Adverse Reactions

Frequency not defined:

Cardiovascular: Bradycardia, cardiac arrhythmia, chest pain, chest tightness, circulatory shock, flushing, hypertension, hypotension, shock, syncope, tachycardia

Central nervous system: Chills, disorientation, dizziness, headache, loss of consciousness, malaise, numbness, paresthesia, seizure, shivering, unresponsive to stimuli

Dermatologic: Diaphoresis, pruritus, skin cyanosis, skin rash, urticaria

Gastrointestinal: Abdominal pain, diarrhea, dysgeusia, nausea, vomiting

Genitourinary: Hematuria

Hematologic & oncologic: Leukocytosis, lymphadenopathy, purpuric rash

Hypersensitivity: Anaphylaxis

Infection: Sterile abscess

Local: Atrophy at injection site (IM), cellulitis at injection site, fibrosis at injection site (IM), inflammation at injection site, injection site phlebitis (IV), local skin discoloration, local soreness/soreness at injection site (IM), pain at injection site (IM), swelling at injection site

Neuromuscular & skeletal: Arthralgia, arthritis, asthenia, back pain, exacerbation of arthritis, myalgia

Respiratory: Acute respiratory distress, bronchospasm, dyspnea, wheezing

Miscellaneous: Fever

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: [US Boxed Warning]: Anaphylactic-type reactions (including fatalities) are associated with parenteral administration of iron dextran. Administer only where resuscitation equipment and personnel trained in detection and treatment of hypersensitivity are available during administration. Administer a test dose prior to the first therapeutic dose. If no signs/symptoms of anaphylactic-type reactions follow the test dose, administer the full therapeutic dose. Monitor for signs/symptoms of hypersensitivity during infusion. Fatal reactions have occurred following a test dose and have occurred in patients who tolerated the test dose. Patients with a history of drug allergy or multiple drug allergies may be at increased risk of anaphylactic-type reactions. The risk of adverse events (including life threatening) was higher with the high-molecular-weight iron dextran formulation (which is no longer commercially available) compared to low-molecular-weight iron dextran (INFeD) (Chertow 2006). Concomitant use of angiotensin-converting enzyme (ACE) inhibitors may also increase the risk of hypersensitivity.
• Infusion reaction: Delayed (1 to 2 days) infusion reaction (including arthralgia, back pain, chills, dizziness, fever, headache, malaise, myalgia, nausea, and/or vomiting) may occur with large doses (eg, total dose infusion) of IV iron dextran; symptoms usually subside within 3 to 4 days.

Disease-related concerns:

• Allergies/asthma: Use with caution in patients with a significant history of allergies and/or asthma.
• Cardiovascular disease: Use with caution in patients with pre-existing cardiovascular disease; iron dextran may exacerbate cardiovascular complications.
• Hepatic impairment: Use with extreme caution in patients with serious hepatic impairment.
• Renal disease/impairment: In patients with chronic kidney disease (CKD) requiring iron supplementation, the IV route is preferred for hemodialysis patients; either oral iron or IV iron may be used for nondialysis and peritoneal dialysis CKD patients, although an initial 1- to 3-month trial of oral iron therapy is recommended (KDIGO 2012). Avoid use during acute kidney infection.
• Rheumatoid arthritis: Patients with rheumatoid arthritis may experience acute exacerbation of joint pain and swelling.

Concurrent drug therapy issues:

• Drug-drug/drug-food interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Anemia in the elderly is often caused by “anemia of chronic disease” or associated with inflammation rather than blood loss. Iron stores are usually normal or increased, with a serum ferritin >50 ng/mL and a decreased total iron binding capacity. IV administration of iron dextran is often preferred over IM in the elderly secondary to a decreased muscle mass and the need for daily injections.
• Pediatric: Intramuscular iron dextran use in neonates may be associated with an increased incidence of gram-negative sepsis.

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: Use iron dextran only in patients where clinical and laboratory evidence has established the iron deficient state is not amenable to oral iron therapy. Discontinue oral iron prior to initiating parenteral iron therapy.
• Carcinogenicity: Cases of tumor development at prior intramuscular injection sites of iron-carbohydrate complexes have been reported.
• Iron overload: Exogenous hemosiderosis may result from excess iron stores; patients with refractory anemias and/or hemoglobinopathies may be prone to iron overload with unwarranted iron supplementation.

Monitoring Parameters

Monitor hemoglobin, hematocrit, reticulocyte count, serum ferritin, serum iron, TIBC; monitor for anaphylaxis/hypersensitivity reaction (during test dose, for 1 hour after test dose, and during and after therapeutic dose)

Cancer patients with anemia: Monitor iron, total iron-binding capacity, transferrin saturation, or ferritin levels at baseline and periodically (Rizzo 2010).

Chronic kidney disease: Monitor transferrin saturation more frequently following a course of IV iron (KDIGO 2012)

Pregnancy

Pregnancy Considerations

Iron dextran may cross the placenta.

Maternal iron requirements increase during pregnancy. Adequate iron concentrations to the fetus can be maintained regardless of maternal iron status, except in severe cases of anemia (IOM 2001). Untreated iron deficiency and iron deficiency anemia (IDA) in a pregnant female may be associated with adverse events, including low birth weight, preterm birth, or increased perinatal mortality (ACOG 95 2008; IOM 2001; Pavord 2012).

In general, treatment of iron deficiency or IDA in pregnancy is the same as in non-pregnant females. The majority of studies note iron therapy improves maternal hematologic parameters; however, information related to clinical outcomes in the mother and neonate is limited (Auerbach 2017a; Reveiz 2011; Siu 2015; Wong 2016). Oral preparations are generally sufficient; however, parenteral iron therapy may be used in females who cannot tolerate or will not take oral iron, in cases of severe iron deficiency, or when malabsorption is present (ACOG 95 2008; Pavord 2012). Due to limited safety data in early pregnancy, use of intravenous iron is generally not started until the second or third trimester (Breymann 2017a; Pavord 2012). Iron dextran has been evaluated for the treatment of IDA in pregnancy (Auerbach 2017a; Reveiz 2011; Wong 2016).

Patient Education

What is this drug used for?

• It is used to treat or prevent low iron in the body.

Frequently reported side effects of this drug

• Injection site pain
• Skin discoloration
• Irritation
• Diarrhea
• Abdominal pain
• Change in taste

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe headache
• Chest pain
• Severe dizziness
• Passing out
• Vision changes
• Severe loss of strength and energy
• Severe nausea
• Vomiting
• Burning or numbness feeling
• Blue/gray skin discoloration
• Swollen glands
• Blood in the urine
• Back pain
• Joint pain
• Chills
• Seizures
• Confusion
• Muscle pain
• Sweating a lot
• Shortness of breath
• Flushing
• Slow heartbeat
• Fast heartbeat
• Abnormal heartbeat
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.