Anaphylactic-type reactions, including fatalities, have followed the parenteral administration of iron dextran injection. Have resuscitation equipment and personnel trained in the detection and treatment of anaphylactic-type reactions readily available during iron dextran administration.
Administer a test dose of iron dextran prior to the first therapeutic dose. If no signs or symptoms of anaphylactic-type reactions follow the test dose, administer the full therapeutic iron dextran dose. During all iron dextran administrations, observe for signs or symptoms of anaphylactic-type reactions. Fatal reactions have been reported following the test dose of iron dextran injection. Fatal reactions have also occurred in situations where the test dose was tolerated.
Patients with a history of drug allergy or multiple drug allergies may be at increased risk of anaphylactic-type reactions to iron dextran.
Use iron dextran only in patients in whom clinical and laboratory investigations have established an iron-deficient state not amenable to oral iron therapy.
Note: Route of administration: IV iron replacement is preferred over oral replacement in several clinical situations (eg, poor GI absorption, lack of response to or poor tolerability of oral iron, need for rapid repletion, chronic kidney disease, active inflammatory bowel disease, cancer, chronic or extensive blood loss) (Auerbach 2021). Dosage expression: Dose is expressed in mg of elemental iron. Test dose: A 25 mg test dose should be administered over ≥30 seconds prior to starting iron dextran therapy; observe for at least 1 hour after test dose prior to administering the remainder of the dose. Some experts administer the test dose over 5 minutes and observe for another 5 to 10 minutes before administering the remainder of the dose (Auerbach 2021).
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).
Iron-deficiency anemia, treatment:
Fixed dose (off-label): IV: 1 g as a single dose; dilute in 250 mL of NS and administer over 1 hour (Auerbach 2011).
Calculated dose (manufacturer's labeling): IV:
Total dose (mL) = (0.0442 × {desired hemoglobin [g/dL] − observed hemoglobin [g/dL]} × IBW [kg]) + (0.26 × IBW [kg])
IBW = Ideal body weight in kg; if actual body weight is less than IBW, use actual body weight.
Note: Total required dose is administered as multiple daily doses of ≤2 mL (100 mg) until the full dose is administered (manufacturer's labeling). Some experts recommend the fixed dose option above (Auerbach 2021).
Iron replacement therapy for blood loss: IM (INFeD, DexIron [Canadian product]), IV (INFeD, DexIron [Canadian product]): Replacement iron (mg) = blood loss (mL) x Hct
Restless legs syndrome (off-label use):
Note: For use as an alternative to oral iron repletion for patients with malabsorption, intolerance, or lack of response to oral therapy, or need for rapid response to therapy; not recommended for initiation of therapy in patients with serum ferritin >100 mcg/L or transferrin saturation (TSAT) ≥45% (Allen 2018).
IV: Test dose of 25 mg, followed 1 hour later by 975 mg infused over 1 to 4 hours. Dose may be repeated at least 12 weeks after initial infusion based on initial response, recurrence of restless legs syndrome symptoms, and if serum ferritin <300 mcg/L and TSAT <45% (Allen 2018).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
Hemodialysis: Dialysis removal of iron dextran is negligible.
There are no dosage adjustments provided in the manufacturer's labeling; use with extreme caution in patients with severe impairment.
(For additional information see "Iron dextran: Pediatric drug information")
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 (Hbn - Hbo) x LBW + (0.26 x LBW).
LBW = lean body weight in kg. Note: For patients weighing 5 to 15 kg, use actual body weight.
Hbn = desired hemoglobin (g/dL) = 12 g/dL if ≤15 kg or 14.8 g/dL if >15 kg.
Hbo = 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, Children, and Adolescents: 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.
There are no dosage adjustments provided in the manufacturer's labeling.
Hemodialysis: Dialysis removal of iron dextran is negligible.
There are no dosage adjustments provided in manufacturer's labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Infed: 50 mg/mL (2 mL)
No
Strength of iron dextran complex is expressed as elemental iron.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection:
Dexiron: 50 mg/mL ([DSC])
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).
Parenteral: Note: A test dose should be administered on the first day of therapy; observe the patient for at least 1 hour for hypersensitivity reaction, then the remainder of the day's dose (dose minus the test dose) should be administered. 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: Use Z-track technique for IM administration (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: Typically infuse test dose over at least 30 seconds; in pediatric total dose infusion trials, the test dose (25 to 30 mg) was infused over 5 to 10 minutes (Mamula 2002; Plummer 2013).
Intermittent doses: Doses may be injected undiluted at a rate not to exceed 50 mg/minute; large or total replacement doses may be diluted and infused over 1 to 6 hours at a maximum rate not to exceed 50 mg/minute (Silverstein 2004).
Total dose infusion: Doses of ≤1,000 mg have been administered over 1 hour (Mamula 2002; Plummer 2013).
Iron deficiency anemia, treatment: Treatment of iron deficiency in adult and pediatric patients ≥4 months of age with intolerance to oral iron or unsatisfactory response to oral iron.
Restless legs syndrome
Iron dextran complex may be confused with ferumoxytol
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Bradycardia, cardiac arrhythmia, chest pain, chest tightness, flushing, hypertension, hypotension, shock, syncope, tachycardia
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, type IV hypersensitivity reaction (large IV doses)
Infection: Sterile abscess
Local: Atrophy at injection site (IM), 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
Nervous system: Chills, disorientation, dizziness, headache, loss of consciousness, malaise, numbness, paresthesia, seizure, shivering, unresponsive to stimuli
Neuromuscular & skeletal: Arthralgia, arthritis, asthenia, back pain, exacerbation of arthritis, myalgia
Respiratory: Apnea, bronchospasm, dyspnea, wheezing
Miscellaneous: Fever
Postmarketing: Hypersensitivity: Severe hypersensitivity reaction
Hypersensitivity to iron dextran or any component of the formulation.
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.
Special populations:
• Older adult: 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.
Use parenteral iron products with caution in premature neonates; necrotizing enterocolitis has been reported; however, no causal relationship established.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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. Risk C: Monitor therapy
Dimercaprol: May enhance the nephrotoxic effect of Iron Preparations. Risk X: Avoid combination
Iron transfer to the fetus may increase following a maternal infusion of iron dextran (Bauminger 1982; Bingham 1983). Iron transfer to the fetus is regulated by the placenta (BSH [Pavord 2020]; NAS 2020).
There is a risk of adverse maternal reactions (eg, anaphylaxis, hypotension, shock) following use of parenteral iron that may result in fetal bradycardia, especially during the second and third trimesters. Although the risk is rare, immediate treatment for anaphylactoid and/or hypersensitivity reactions should be available (BSH [Pavord 2020]).
Maternal iron requirements increase during pregnancy. Untreated iron deficiency and iron deficiency anemia (IDA) in pregnant patients are associated with adverse pregnancy outcomes, including low birth weight, preterm birth, and increased perinatal mortality (ACOG 2021; BSH [Pavord 2020]). Maternal iron deficiency is also associated with fatigue, increased risk of postpartum depression, and possibly postpartum hemorrhage (BSH [Pavord 2020]).
Oral and parenteral iron are effective at replacing iron stores in pregnant patients (ACOG 2021), Most studies note iron therapy improves maternal hematologic parameters; however, data related to clinical outcomes in the mother and neonate are limited (FIGO 2019; NAS 2020; USPSTF [Siu 2015]). Parenteral iron therapy may be used in pregnant patients who cannot tolerate or respond to oral iron, when iron deficiency occurs later in pregnancy, or when malabsorption is present (ACOG 2021; BSH [Pavord 2020]).
Iron dextran has been evaluated for the treatment of IDA in pregnancy (Auerbach 2017a; Darwish 2019; Reveiz 2011; Rogozińska 2021; Wong 2016). However, due to limited safety data in early pregnancy, use of IV iron is generally not started until the second or third trimester (ACOG 2021; BSH [Pavord 2020]; FIGO 2019).
IV iron may be considered for the treatment of restless legs syndrome in pregnant patients with serum ferritin <30 ng/mL who have failed oral iron; use of IV iron should be avoided during the first trimester (Picchietti 2015; Schneider 2015).
Trace amounts of iron dextran are present in breast milk.
Iron is present in breast milk. Endogenous iron concentrations in breast milk vary by postpartum age and are lower than concentrations in the maternal plasma (Dorea 2000; Emmett 1997). Breast milk concentrations of iron are maintained in lactating patients with mild to moderate iron deficiency anemia (IDA), but concentrations decrease if IDA is moderate to severe (El-Farrash 2012) or severe (Kumar 2008).
Iron dextran complex has been evaluated for the treatment of postpartum IDA (Daniilidis 2011; Iyoke 2017).
Iron deficiency and IDA are associated with adverse effects in postpartum patients (eg, altered cognition, depression, fatigue), which may influence interactions with the infant. Iron supplementation in the postpartum patient should be initiated as soon as possible following delivery when gestational anemia is a concern (WHO 2016). Parenteral iron therapy may be used in postpartum patients with uncorrected anemia at delivery who cannot tolerate, do not respond to, or are noncompliant with oral iron therapy, or the severity of anemia requires prompt management (BSH [Pavord 2020]).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. The World Health Organization considers iron dextran, when used for anemia, to be compatible with breastfeeding (WHO 2002).
Hemoglobin, hematocrit, reticulocyte count, serum ferritin, serum iron, TIBC, transferrin saturation; 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).
Hemoglobin: Adults:
Males: 13.5 to 16.5 g/dL
Females: 12.0 to 15.0 g/dL
Serum iron: 40 to 160 mcg/dL
Total iron binding capacity: 230 to 430 mcg/dL
Transferrin: 204 to 360 mg/dL
Percent transferrin saturation: 20% to 50%
The released iron, from the plasma, eventually replenishes the depleted iron stores in the bone marrow where it is incorporated into hemoglobin
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
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
Half-life elimination: 48 hours
Excretion: Urine and feces via reticuloendothelial system
Solution (Infed Injection)
50 mg/mL (per mL): $19.32
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