CASE 92-1, QUESTION 7: When would parenteral iron therapy be indicated for H.P.?
Several indications exist for parenteral iron administration. Causes of oral therapy
failure can include nonadherence, misdiagnosis, inflammatory conditions,
malabsorption (e.g., atrophic gastritis, radiation enteritis, gastric bypass, celiac
disease), the need for rapid iron repletion, and continuing blood loss equal to or
greater than the rate of RBC production.
3,4 Besides failure to respond to oral therapy,
other indications for parenteral iron administration include intolerance to oral
therapy, required antacid therapy, or significant blood loss in patients refusing
transfusion. In H.P.’s case, intolerance, continued blood loss, long-term antacid
therapy, and malabsorption may be potential indications for use and, if documented,
she would be a candidate for injectable iron.
CASE 92-1, QUESTION 8: What is the preferred formulation of parenteral iron administration?
Iron can be given parenterally in the form of ferric gluconate, iron dextran, iron
sucrose, ferric carboxymaltose, and ferumoxytol (Table 92-8).
between agents reveals similar efficacy with differences in cost analysis from
diverse administration schedules. Iron dextran and ferric carboxymaltose are US
Food and Drug Administration (FDA)-approved for the treatment of iron deficiency
when oral supplementation is impossible or ineffective. All parenteral iron products
can be administered undiluted slowly as an intravenous (IV) push, or diluted and
administered by infusion; although not included in the FDA-approved labeling, iron
dextran injection is commonly diluted in 500 mL of 0.9% NaCl and administered by
Iron dextran is also the only product that may be given intramuscularly
(IM). This route may be preferred in a few instances, such as in patients with limited
IV access. Although the data are limited, infusion of the total dose (total estimated
iron deficit) of iron dextran is given in clinical practice and has proved to be
15 The total dose method of administration can be associated
with a higher prevalence of fever, malaise, flushing, and myalgias. Because of the
potential for anaphylaxis with iron dextran, an IM or IV test dose should be given.
The test dose for adults is 25 mg of iron dextran. Although anaphylactic reactions
usually are evident within a few minutes if they occur, it is recommended that a
period of 1 hour or longer elapse before the remaining portion of the initial dose be
given. Subsequent use of test doses should be considered during iron dextran therapy
Drug Interactions with Iron Salts
Iron salts ↓ AHA chelates heavy metals, notably iron. The absorption
of iron may be decreased. When iron is indicated,
administer intramuscularly (IM).
Antacids Iron salts ↓ GI absorption of iron may be reduced.
Ascorbic acid Iron salts ↑ Ascorbic acid at doses ≥200 mg have been shown to
enhance the absorption of iron ≥30%.
Calcium salts Iron salts ↓ GI absorption of iron may be reduced. When possible,
separate administration times.
Chloramphenicol Iron salts ↑ Serum iron levels may be increased.
Digestive enzymes Iron salts ↓ The serum iron response to oral iron may be decreased
by concomitant pancreatic extracts.
antagonists Iron salts ↓ GI absorption of iron may be reduced.
Proton pump inhibitors Iron salts ↓ GI absorption of iron may be reduced.
Trientine Iron salts ↓ The 2 agents inhibit the absorption of each other. If iron is
needed, administer the agents at least 2 hours apart.
Iron salts Captopril ↓ Concomitant use within 2 hours may promote formation
of inactive captopril disulfide dimer.
↓ Iron supplements and foods fortified with iron may reduce
the absorption of cefdinir 80% and 30%, respectively. If
iron supplements are needed during cefdinir therapy,
cefdinir should be taken 2 hours before or after the
supplement. Iron-fortified infant formula (elemental iron
2.2 mg per 6 oz) has no effect on cefdinir absorption.
↓ GI absorption of fluoroquinolones may be decreased
because of formation of iron–quinolone complex. Avoid
coadministration of these drugs. (See individual
fluoroquinolone monographs for administration
Iron salts Levodopa ↓ Levodopa appears to form chelates with iron salts,
decreasing levodopa absorption and serum levels.
Iron salts Levothyroxine ↓ The efficacy of levothyroxine may be decreased, resulting
in hypothyroidism. Avoid coadministration.
Iron salts Methyldopa ↓ Extent of methyldopa absorption may be decreased,
possibly resulting in decreased efficacy.
↓ Absorption of mycophenolate mofetil may be decreased.
Avoid simultaneous administration.
Iron salts Penicillamine ↓ Marked reduction in GI absorption of penicillamine may
occur, possibly because of chelation.
Iron salts Tetracyclines ↓ Concomitant use within 2 hours may decrease absorption
and serum levels of tetracyclines. Absorption of iron salts
↓ Absorption of thyroid hormones may be decreased. Avoid
a↑ = object drug increased; ↓ = object drug decreased.
Source: Facts & Comparisons eAnswers. http://online.factsandcomparisons.com/MonoDisp.aspx?
monoID=fandc-hcp11143#IronSaltsDrugInteractions. Accessed June 12, 2015.
Ferric gluconate, iron sucrose, and ferumoxytol are parenteral iron formulations
that are FDA-approved for the treatment of iron deficiency anemia in patients with
chronic kidney disease undergoing chronic hemodialysis. Ferric carboxymaltose is
indicated for treatment of iron deficiency anemia in nondialysis-dependent chronic
kidney disease. A test dose is not required for these agents due to the lower
incidence of serious anaphylactoid reactions. Iron requirements in these patients
typically exceed 1 to 2 g and, therefore, multiple doses of ferric gluconate and iron
sucrose are needed to achieve the total dose of iron.
Comparison of Parenteral Iron Preparations
Preparation Dosage Form Usual Dose Maximum Dose
Weight ≥50 kg: 750 mg per dose
Weight <50 kg: 15 mg/kg per dose
Ferumoxytol Solution for injection: 30
510 mg per dose; repeat once 3–8 days
Iron dextran Solution for injection: 50
Test dose: 25 mg; followed by up to 75 mg
(dose based on patient weight)
Iron sucrose Solution for injection: 20
HD: 100 mg during consecutive HD
CKD, nondialysis: 200 mg on 5 different
occasions over 14 days; 500 mg once on
CKD, PD: 300 mg IV days 1 and 14, then
125 mg per dose (usually repeated to
CKD: chronic kidney disease; HD: hemodialysis; PD: peritoneal dialysis.
Source: Facts & Comparisons eAnswers. http://online.factsandcomparisons.com/MonoDisp.aspx?
In general, rates of adverse effects are similar among agents. Patients should be
monitored for hypersensitivity reactions for at least 30 minutes after administration of
The total dose of iron dextran to be administered can be determined using the
where Hgb is the patient’s measured Hgb (g/dL).
The equation uses the person’s weight (in pounds) and assumes that an Hgb of 14.8
g/dL is 100% of normal. Children weighing less than 30 pounds should be given 80%
of the calculated dose because the normal mean Hgb in this population is lower.
For patients with anemia resulting from blood loss (e.g., hemorrhagic diathesis) or
patients receiving chronic dialysis, the iron requirement is based on the estimate of
iron contained in the blood lost. In this case, the following equation should be used:
This formula assumes that 1 mL of normochromic blood contains 1 mg of iron.
After parenteral administration, iron dextran is cleared by the reticuloendothelial
cells and processed. The iron is then released back into the plasma and bone
marrow. Because the rate of iron incorporation into Hgb does not exceed that
achieved by oral iron therapy, the response time is similar to that of oral iron
therapy, and the Hgb can be expected to increase at a rate of 1 to 2 g/dL/week during
the first 2 weeks and by 0.7 to 1 g/dL/week thereafter until normal values are
CASE 92-1, QUESTION 10: What side effects can be expected from parenteral iron therapy?
Overall adverse reactions reported with parenteral iron administration are rare.
Anaphylactoid reactions occur in less than 1% of patients treated with parenteral iron
therapy and are more commonly associated with iron dextran and ferumoxytol than
with ferric gluconate and iron sucrose.
In a small study comparing iron dextran to
ferric carboxymaltose, patients experienced significantly fewer immune-related
18 Other side effects seen with parenteral iron agents include chest
pain, headache, hypotension, nausea and vomiting, cramps, and diarrhea.
Megaloblastic anemia is a common disorder that can have several causes, including
anemias associated with vitamin B12 or folic acid deficiency or metabolic or
inherited defects associated with a decreased ability to use vitamin B12 or folic
Megaloblastosis results from impaired DNA synthesis in replicating cells, which
is signaled by a large immature nucleus.
19 RNA and protein synthesis remain
unaffected, and the cytoplasm matures normally. Megaloblastic changes can be
observed microscopically in RBC and in proliferating cells (e.g., in the cervix, skin,
GI tract). The extent of RBC macrocytosis is reported as MCV, calculated as shown
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