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Treatment of anemia due to iron deficiency
Stanley L Schrier, MD

UpToDate performs a continuous review of over 375 journals and other resources. Updates are added as important new information is published. The literature review for version 15.3 is current through August 2007; this topic was last changed on June*27,*2007. The next version of UpToDate (16.1) will be released in March 2008.

INTRODUCTION*—*Treatment of iron deficiency anemia must include both attempts to identify and treat the cause of the deficiency (eg, blood loss, poor iron absorption) as well as the administration of iron. The causes and diagnosis of this disorder are discussed separately. (See "Causes and diagnosis of anemia due to iron deficiency").

The diagnosis and treatment of iron deficiency in dialysis patients is a specialized subject, and is presented separately. (See "Iron balance in predialysis, peritoneal dialysis, and home hemodialysis patients" and see "Use of iron preparations in hemodialysis patients" and see "Diagnosis of iron deficiency in chronic kidney disease").

GENERAL PRINCIPLES*—*Oral iron usually provides a safe, cheap and effective means of restoring iron balance. There are a few simple principles governing the use of oral iron [1]: Iron is absorbed best from the duodenum and proximal jejunum. Therefore, the more expensive enteric coated or sustained release capsules, which release iron further down in the GI tract, are counterproductive. Iron salts should not be given with food because the phosphates, phytates, and tannates in food bind the iron and impair its absorption (show table 1). Iron should be given two hours before, or four hours after, ingestion of antacids. Iron is best absorbed as the ferrous (Fe2+) salt in a mildly acidic medium. As a result, we usually add a 250 mg ascorbic acid tablet at the time of iron administration to enhance the degree of iron absorption. The iron preparation used should be based upon cost and effectiveness with minimal side effects. The cheapest preparation is iron sulfate; each tablet contains 325 mg of iron salts, of which 65 mg is elemental iron [2]. Gastrointestinal tract symptoms (eg, abdominal discomfort, nausea/vomiting, diarrhea/constipation) suffered by some patients seem to be directly related to the amount of elemental iron ingested [3]. Thus, the reported low incidence of side effects for some preparations can be explained by their low elemental iron content. For example, a 325 mg tablet of ferrous gluconate contains 36 mg of elemental iron, or 55 percent of the amount of elemental iron in a 325 mg tablet of ferrous sulfate. Patients with persistent gastric intolerance may tolerate ferrous sulfate elixir, which provides 44 mg of elemental iron per 5 mL. Patients can titrate the dose up or down to the level at which the gastrointestinal symptoms become acceptable.

ORAL IRON THERAPY*—*A large number of iron-containing preparations are available for the treatment of iron deficiency anemia; some contain other minerals and vitamins, while others may be enteric-coated or have slow-release properties. The latter are especially to be avoided as they may be excreted intact in the stool or release iron too far down the intestinal tract to be maximally effective.

A number of factors can inhibit the absorption of iron salts, including the use of antacids, certain antibiotics (eg, quinolones, tetracycline), and the ingestion of iron along with cereals, dietary fiber, tea, coffee, eggs, or milk.

Choice of preparation and expected response*—*The most appropriate oral iron therapy is use of a tablet containing ferrous salts, such as: Ferrous fumarate — 106 mg elemental iron/tablet Ferrous sulfate — 65 mg elemental iron/tablet Ferrous gluconate — 28 to 36 mg iron/tablet

The recommended daily dose for the treatment of iron deficiency in adults is in the range of 150 to 200 mg/day of elemental iron; there is no evidence that one iron preparation is more effective than another.

A single 325 mg ferrous sulfate tablet taken orally three times daily between meals provides 195 mg of elemental iron per day. This regimen should lead to a modest reticulocytosis beginning in approximately seven days and a rise in the hemoglobin concentration of approximately 2 g/dL over the ensuing three weeks.

Side effects*—*Approximately 10 to 20 percent of patients may complain of nausea, constipation, epigastric distress and/or vomiting after taking oral iron preparations. There are a number of treatment options for such patients: The patient may take an iron preparation containing a smaller dose of elemental iron (eg, switching from ferrous sulfate to ferrous gluconate), or may switch from a tablet to a liquid preparation, the dose of which (44 mg elemental iron per 5 mL) can be easily titrated by the patient (see "General principles" above). The patient may slowly increase the dose from one tablet per day to the recommended three to four times per day, as tolerated. The iron may be taken with meals, although this will decrease absorption somewhat

One or more of these maneuvers should suffice. Parenteral iron therapy should be reserved for the rare patient unable to tolerate even modest doses of oral iron, or in patients whose level of continued bleeding exceeds the ability of the gastrointestinal tract to absorb iron (see "Parenteral iron therapy" below).

Duration of treatment*—*There is disagreement as to how long to continue iron therapy: Some physicians stop when the hemoglobin level becomes normal, so that further blood loss will cause anemia and alert the patient and physician to the return of the problem which caused the iron deficiency in the first place Others believe that it is wise to treat for about six months after the hemoglobin normalizes, in order to completely replenish iron stores

Our practice is to individualize the duration of iron replacement. As an example, it makes sense to fully replenish iron stores in a patient who became iron deficient as a consequence of multiple pregnancies. On the other hand, we stop therapy once the hemoglobin concentration is normalized in a patient who has occult gastrointestinal bleeding. In this setting, the return of iron deficiency is an important clue that bleeding has recurred.