Page 609 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 33 Agents Used in Cytopenias; Hematopoietic Growth Factors 595

The most common cause of iron deficiency in adults is blood gastrointestinal adverse effects with one iron salt than another
loss. Menstruating women lose about 30 mg of iron with each and benefit from changing preparations. Patients taking oral iron
menstrual period; women with heavy menstrual bleeding may develop black stools; this has no clinical significance in itself but
lose much more. Thus, many premenopausal women have low may obscure the diagnosis of continued gastrointestinal blood
iron stores or even iron deficiency. In men and postmenopausal loss.
women, the most common site of blood loss is the gastrointestinal
tract. Patients with unexplained iron deficiency anemia should be 2. Parenteral iron therapy—Parenteral therapy should be
evaluated for occult gastrointestinal bleeding. reserved for patients with documented iron deficiency who are
unable to tolerate or absorb oral iron and for patients with exten-
B. Treatment sive chronic anemia who cannot be maintained with oral iron
Iron deficiency anemia is treated with oral or parenteral iron alone. This includes patients with advanced chronic renal disease
preparations. Oral iron corrects the anemia just as rapidly and requiring hemodialysis and treatment with erythropoietin, various
completely as parenteral iron in most cases if iron absorption postgastrectomy conditions and previous small bowel resection,
from the gastrointestinal tract is normal. An exception is the high inflammatory bowel disease involving the proximal small bowel,
requirement for iron of patients with advanced chronic kidney and malabsorption syndromes.
disease who are undergoing hemodialysis and treatment with The challenge with parenteral iron therapy is that parenteral
erythropoietin; for these patients, parenteral iron administration administration of inorganic free ferric iron produces serious dose-
is preferred. dependent toxicity, which severely limits the dose that can be
administered. However, when the ferric iron is formulated as a
1. Oral iron therapy—A wide variety of oral iron preparations is colloid containing particles with a core of iron oxyhydroxide sur-
available. Because ferrous iron is most efficiently absorbed, ferrous rounded by a core of carbohydrate, bioactive iron is released slowly
salts should be used. Ferrous sulfate, ferrous gluconate, and ferrous from the stable colloid particles. In the United States, the three
fumarate are all effective and inexpensive and are recommended traditional forms of parenteral iron are iron dextran, sodium
for the treatment of most patients. ferric gluconate complex, and iron sucrose. Two newer prepara-
Different iron salts provide different amounts of elemental tions are available (see below).
iron, as shown in Table 33–3. In an iron-deficient individual, Iron dextran is a stable complex of ferric oxyhydroxide and
about 50–100 mg of iron can be incorporated into hemoglobin dextran polymers containing 50 mg of elemental iron per milliliter
daily, and about 25% of oral iron given as ferrous salt can be of solution. It can be given by deep intramuscular injection or by
absorbed. Therefore, 200–400 mg of elemental iron should be intravenous infusion, although the intravenous route is used most
given daily to correct iron deficiency most rapidly. Patients unable commonly. Intravenous administration eliminates the local pain
to tolerate such large doses of iron can be given lower daily doses and tissue staining that often occur with the intramuscular route
of iron, which results in slower but still complete correction of and allows delivery of the entire dose of iron necessary to correct
iron deficiency. Treatment with oral iron should be continued for the iron deficiency at one time. Adverse effects of intravenous
3–6 months after correction of the cause of the iron loss. This iron dextran therapy include headache, light-headedness, fever,
corrects the anemia and replenishes iron stores. arthralgias, nausea and vomiting, back pain, flushing, urticaria,
Common adverse effects of oral iron therapy include nausea, bronchospasm, and, rarely, anaphylaxis and death. Owing to the
epigastric discomfort, abdominal cramps, constipation, and diar- risk of a hypersensitivity reaction, a small test dose of iron dextran
rhea. These effects are usually dose-related and often can be over- should always be given before full intramuscular or intravenous
come by lowering the daily dose of iron or by taking the tablets doses are given. Patients with a strong history of allergy and
immediately after or with meals. Some patients have less severe patients who have previously received parenteral iron dextran
are more likely to have hypersensitivity reactions after treatment
with parenteral iron dextran. The iron dextran formulations
TABLE 33–3 Some commonly used oral iron used clinically are distinguishable as high-molecular-weight and
preparations.
low-molecular-weight forms. In the United States, the INFeD
preparation is a low-molecular-weight form while Dexferrum is
Usual Adult Dosage
Elemental for Treatment of a high-molecular-weight form. Clinical data—primarily from
Tablet Iron per Iron Deficiency observational studies—indicate that the risk of anaphylaxis is
Preparation Size Tablet (Tablets per Day) largely associated with high-molecular-weight formulations.
Ferrous sulfate, 325 mg 65 mg 2–4 Sodium ferric gluconate complex and iron-sucrose complex
hydrated are alternative parenteral iron preparations. Ferric carboxymalt-
Ferrous sulfate, 200 mg 65 mg 2–4 ose is a colloidal iron preparation embedded within a carbohy-
desiccated drate polymer. Ferumoxytol is a superparamagnetic iron oxide
Ferrous 325 mg 36 mg 3–4 nanoparticle coated with carbohydrate. The carbohydrate shell is
gluconate removed in the reticuloendothelial system, allowing the iron to
Ferrous 325 mg 106 mg 2–3 be stored as ferritin, or released to transferrin. Ferumoxytol may
fumarate interfere with magnetic resonance imaging (MRI) studies. Thus if