Treatment Show
Approach ConsiderationsMedical care starts with establishing the diagnosis and reason for the iron deficiency. In most patients, the iron deficiency should be treated with oral iron therapy, and the underlying etiology should be corrected so the deficiency does not recur. However, avoid giving iron to patients who have a microcytic iron-overloading disorder (eg, thalassemia, sideroblastic anemia). Do not administer parenteral iron therapy to patients who should be treated with oral iron, as anaphylaxis may result. Uncommonly, postmenopausal women are unresponsive to iron supplementation, including parenteral iron, because they have primary defective iron reutilization due to androgen deficiency. This condition responds only to androgen replacement. Danazol is a reasonable choice for these patients, as it is less masculinizing. [9, 10] Transfer of a patient rarely is required for treatment of simple iron deficiency anemia. However, it may be necessary to identify the etiology of the anemia, such as occult blood loss undetected with chemical testing of stool specimens; for identification of a source of bleeding that requires endoscopic examinations or angiography; or for treatment of an underlying major illness (eg, neoplasia, ulcerative colitis). British Society of Gastroenterology guidelines recommend starting treatment of iron deficiency anemia with one tablet of ferrous sulfate, fumarate, or gluconate per day. If that is not tolerated, the patient can take one tablet every other day or try a different iron preparation. Parenteral iron should be considered when oral iron is contraindicated, ineffective, or not tolerated. Blood transfusions should be reserved for patients with severe symptoms, circulatory compromise, or both. [16] Treatment guidelines from the American College of Physicians (ACP) for adult patients with anemia and iron deficiency include the following [17] :
Go to Anemia, Sideroblastic Anemias, and Chronic Anemia for more information on these topics. Iron TherapyOral ferrous iron salts are the most economical and effective medication for the treatment of iron deficiency anemia. Of the various iron salts available, ferrous sulfate is the one most commonly used. Although the traditional dosage of ferrous sulfate is 325 mg (65 mg of elemental iron) orally three times a day, lower doses (eg, 15-20 mg of elemental iron daily) may be as effective and cause fewer side effects. To promote absorption, patients should avoid tea and coffee and may take vitamin C (500 units) with the iron pill once daily. [18] However, a randomized trial in 140 adult patients with iron deficiency anemia found that oral iron taken alone and oral iron taken with 200 mg of vitamin C produced equivalent increases in hemoglobin and serum ferritin levels and equivalent rates of adverse events. [19] However, a study by Moretti et al suggests that the standard dosing of iron supplements may be counterproductive. Their research focuses on the role of hepcidin, which regulates systemic iron balance, partly in response to plasma iron levels. They found that when a large oral dose of iron is taken in the morning, the resulting increase in the plasma iron level stimulates an increase in hepcidin, which in turn will interfere with the absorption of an iron dose taken later in the day; indeed, suppression of iron absorption could last as long as 48 hours. [20, 21] In one part of their study, twice-daily doses of 60 mg or greater resulted in an increase in serum hepcidin levels after the first dose and a 35-45% decrease in the amount of iron that was absorbed from the second dose. With increasing doses, study subjects showed an increase in the absolute amount of iron absorbed, but a decrease in the fraction of the dose that was absorbed. A six-fold increase in iron dose (from 40 mg to 240 mg) resulted in only a three-fold increase in iron absorbed. In another part of the study, total iron absorbed from a morning and an afternoon dose on one day plus a morning dose the next day was not significantly greater than absorption from two consecutive morning doses. [20] Moretti et al concluded that providing lower dosages and avoiding twice-daily dosing will maximize fractional iron absorption, and that their results support supplementation with 40-80 mg of iron taken every other day. A possible additional benefit of this schedule may be that improving absorption will reduce gastrointestinal exposure to unabsorbed iron and thereby reduce adverse effects from supplements. [20, 21] A subsequent longer-term study confirmed that in iron-depleted women, taking iron supplements daily in divided doses increases serum hepcidin and reduces iron absorption, whereas taking iron supplements on alternate days and in single doses optimizes iron absorption. [22] Stoffel et al also concluded that alternate-day dosing of oral iron supplements may be preferable because it sharply increases fractional iron absorption. In their study, conducted in 19 women with iron deficiency anemia, total iron absorption from a single 200-mg dose given on alternate days was approximately twice that from 100 mg given on consecutive days (P < 0.001). [23] Claims are made that other iron salts (eg, ferrous gluconate) are absorbed better than ferrous sulfate and have less morbidity. Generally, the toxicity is proportional to the amount of iron available for absorption. If the quantity of iron in the test dose is decreased, the percentage of the test dose absorbed is increased, but the quantity of iron absorbed is diminished. Ferric citrate (Auryxia) gained US Food and Drug Administration (FDA) approval in November 2017 for treatment of iron deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis. Each tablet of ferric citrate 1 gram is equivalent to 210 mg of ferric iron. Approval was based on results from a 24-week placebo-controlled phase 3 clinical trial in 234 adults with stage 3-5 non–dialysis-dependent CKD. Trial participants had hemoglobin levels of 9-11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements. The starting dose in the study was 3 tablets daily with meals; the mean dose was 5 tablets per day. Importantly, during the study, patients were not allowed to receive any intravenous or oral iron, or erythropoiesis-stimulating agents (ESAs). Significant increases in hemoglobin levels of > 1 g/dL at any point during the 16-week efficacy period occurred in 52.1% of patients taking ferric citrate compared with 19.1% in the placebo group). [24] Some authors advocate the use of carbonyl iron because of the greater safety for children who ingest their mothers’ medication. Decreased gastric toxicity is claimed but not clearly demonstrated in human trials. Bioavailability is approximately 70% of a similar dose of ferrous sulfate. In July 2019, the FDA approved ferric maltol (Accrufer) for treatment of iron deficiency anemia in adults. Under the brand name Feraccru, ferric maltol is approved in the European Union for treatment in adults and in Switzerland for treatment in adults with inflammatory bowel disease (IBD). The FDA approval was based on 3 placebo-controlled trials (AEGIS 1 and 2 [IBD], AEGIS 3 [nondialysis CKD]). Ferric maltol improved Hb from baseline by 2.18 g/dL in AEGIS 1 and 2 and in AEGIS 3 by 0.52 g/dL. [25, 26] Additionally, primary analysis from the phase IIIb AEGIS-H2H study showed oral ferric maltol to be noninferior to IV ferric carboxymaltose in patients with IBD. Further analysis and peer review of this study are in progress as of July 2019. Ferric maltol is an alternative to IV iron for patients that cannot tolerate salt-based oral iron therapies and wish to avoid parenteral treatment. The usual benchmark for successful iron supplementation is a 2-g/dL increase in the hemoglobin (Hb) level in 3 weeks. [27] However, a meta-analysis of five randomized controlled trials concluded that in patients receiving oral iron supplementation, an Hb measurement on day 14 that shows an increase of 1.0 g/dL or more over baseline is an accurate predictor of longer-term and sustained response to continued oral therapy. The authors suggest that, "Day-14 Hb may be a useful tool for clinicians in determining whether and when to transition patients from oral to IV iron." [28] Parenteral iron therapyIron products that are administered parenterally include the following:
Reserve parenteral iron for patients who are either unable to absorb oral iron or who have increasing anemia despite adequate doses of oral iron. It is expensive and has greater morbidity than iron preparations taken orally. Parenteral iron has been used safely and effectively in patients with IBD (eg, ulcerative colitis, Crohn disease), [29] in whom ferrous sulfate preparations may aggravate their intestinal inflammation. In 2013, the FDA approved ferric carboxymaltose injection (Injectafer) for the intravenous (IV) treatment of iron deficiency anemia in adults who either cannot tolerate or have not responded well to oral iron. The drug is also indicated for the treatment of iron deficiency anemia in adults with non–dialysis-dependent CKD. Approval was based on two clinical studies in which the drug was given at a dose of 15 mg/kg body weight, up to a maximum of 750 mg, on two occasions at least 7 days apart, up to a maximum cumulative dose of 1500 mg of iron. [30, 31, 32] A review of the safety of IV iron preparations, particularly in patients with CKD, by Kalra and Bhandari concluded that high molecular weight iron dextrans are associated with increased risks, so their use for IV therapy should be avoided. The second- and third-generation IV irons are considered equally efficacious in treating iron deficiency in equivalent doses, but iron isomaltoside seems to have a lower frequency of serious and severe hypersensitivity reactions. [33] Feraheme (ferumoxytol injection), a hematinic, was initially approved by the FDA in 2009 to treat iron deficiency anemia in adults with CKD. Ferumoxytol injection consists of a superparamagnetic iron oxide that is coated with a carbohydrate shell, which helps isolate the bioactive iron from plasma components until the iron-carbohydrate complex enters the reticuloendothelial system macrophages of the liver, spleen, and bone. The released iron then either enters the intracellular storage iron pool (eg, ferritin) or is transferred to plasma transferrin for transport to erythroid precursor cells for incorporation into hemoglobin. [34] In 2018, the FDA expanded the indication for ferumoxytol injection to include all eligible adults with iron deficiency anemia who have intolerance or unsatisfactory response to oral iron. Expanded approval was based on data from two phase 3 trials comparing ferumoxytol and iron sucrose, as well as data from a phase 3 trial comparing ferumoxytol with ferric carboxymaltose injection. In the phase 3 double-blind safety and efficacy study (n= 609) comparing ferumoxytol to iron sucrose, ferumoxytol treatment-emergent adverse events were mainly mild to moderate. Ferumoxytol was effective and well tolerated in patients with iron deficiency anemia of any underlying cause in whom oral iron was ineffective or could not be used. [35] Ferric derisomaltose (Monoferric) was approved by the FDA in January 2020 for iron deficiency anemia in adults who have intolerance to oral iron or have had unsatisfactory response to oral iron. Efficacy was established in 2 clinical trials (n = 1550) that showed noninferiority of ferric derisomaltose compared with iron sucrose; the trials included patients with chronic renal impairment (estimated glomerular filtration rate [eGFR] 15-59 mL/min) and those receiving either no erythropoiesis-stimulating agents (ESAs) or ESAs at a stable dose. [36] The safety of parenteral iron treatment was demonstrated in two trials that compared ferric derisomaltose with iron sucrose in 3050 patients with iron deficiency anemia: the FERWON-IDA trial, in patients with iron deficiency anemia, due to a broad variety of clinical diagnoses, and intolerance or lack of response to oral iron or a screening hemoglobin concentration sufficiently low to require rapid repletion of iron stores; and the FERWON‐NEPHRO trial, in patients with iron deficiency anemia due to non‐dialysis‐dependent CKD. Both trials achieved the co-primary safety endpoint, with a frequency of serious or severe hypersensitivity reactions of 0.3% during or after the first dose. In addition, the incidence rate of composite cardiovascular adverse events (hpertension, congestive heart failure, atrial fibrillation) was 2.5% in the ferric derisomaltose group and 4.1% in the iron sucrose group. [37] Ferric pyrophosphate citrate (Triferic) is added to the bicarbonate concentrate of the hemodialysate to maintain hemoglobin in adult patients with hemodialysis-dependent CKD. It was approved by the FDA in 2015 as an iron replacement product in adult patients receiving long-term maintenance hemodisalysis. [38] Management of HemorrhageSurgical treatment consists of stopping hemorrhage and correcting the underlying defect so that it does not recur. This may involve surgery for treatment of either neoplastic or nonneoplastic disease of the gastrointestinal (GI) tract, the genitourinary (GU) tract, the uterus, and the lungs. Reserve transfusion of packed red blood cells (RBCs) for patients who either are experiencing significant acute bleeding or are in danger of hypoxia and/or coronary insufficiency. Dietary MeasuresOn a worldwide basis, diet is the major cause of iron deficiency. However, to suggest that iron-deficient populations correct the problem by the addition of significant quantities of meat to their diet is unrealistic. The addition of nonheme iron to national diets has been initiated in some areas of the world. Problems encountered in these enterprises include changes in taste and appearance of food after the addition of iron and the need to supplement foodstuffs that are consumed by most of the population in predictable quantities. In addition, many dietary staples, such as bread, contain iron chelators that markedly diminish the absorption of the iron supplement (phosphates, phytates, carbonates, oxalates, tannates). In North America and Europe, persons on an iron-poor diet need to be identified and counseled on an individual basis. Educate older individuals on a “tea and toast” diet about the importance of improving their diet (for example, tea strongly blocks iron absorption), and place them in contact with community agencies that will provide them with at least one nutritious meal daily. Patients who have diet-related iron deficiency due to pica need to be identified and counseled to stop their consumption of clay and laundry starch. Activity RestrictionRestriction of activity is usually not required. Patients with moderately severe iron deficiency anemia and significant cardiopulmonary disease should limit their activities until the anemia is corrected with iron therapy. If these patients become hypoxic or develop evidence of coronary insufficiency, they should be hospitalized and placed on bed rest until improvement of their anemia can be accomplished by transfusion of packed RBCs. Obviously, such decisions must be made on an individual basis and will depend on the severity of the anemia and the comorbid conditions. March hemoglobinuria can produce iron deficiency, and its treatment requires modification of activity. Cessation of jogging or wearing sneakers while running usually diminishes the hemoglobinuria. PreventionCertain populations are at sufficiently high risk for iron deficiency to warrant consideration for prophylactic iron therapy. These include pregnant women, women with menorrhagia, [39] consumers of a strict vegetarian diet, infants, [40] adolescent girls, and regular blood donors. Pregnant women have been given supplemental iron since World War II, often in the form of all-purpose capsules containing vitamins, calcium, and iron. If the patient is anemic (hemoglobin < 11 g/dL), administer the iron at a different time of day than calcium because calcium inhibits iron absorption. The practice of routinely administering iron to pregnant females in affluent societies has been challenged. Nevertheless, providing prophylactic iron therapy during the last half of pregnancy continues to be advisable, except in settings where careful follow-up for anemia and methods for measurement of serum iron and ferritin are readily available. Iron supplementation of the diet of infants is advocated. Premature infants require more iron supplementation than term infants. Infants weaned early and fed bovine milk require more iron because the higher concentration of calcium in cow milk inhibits absorption of iron. Usually, infants receive iron from fortified cereal. Additional iron is present in commercial milk formulas. Iron supplementation in populations living on a largely vegetarian diet is advisable because of the lower bioavailability of inorganic iron than heme iron. The addition of iron to basic foodstuffs in affluent nations where meat is an important part of the diet is of questionable value and may be harmful. The gene for familial hemochromatosis (HFe gene) is prevalent (8% of the US white population). Excess body iron is postulated to be important in the etiology of coronary artery disease, strokes, certain carcinomas, and neurodegenerative disorders because iron is important in free radical formation. ConsultationsSurgical consultation often is needed for the control of hemorrhage and treatment of the underlying disorder. In the investigation of a source of bleeding, consultation with certain medical specialties may be useful to identify the source of bleeding and to provide control. Among the medical specialties, gastroenterology is the most frequently sought consultation. Endoscopy has become a highly effective tool in identifying and controlling GI bleeding. If bleeding is brisk, angiographic techniques may be useful in identifying the bleeding site and controlling the hemorrhage. Radioactive technetium labeling of autologous erythrocytes also is used to identify the site of bleeding. Unfortunately, these radiographic techniques do not detect bleeding at rates less than 1 mL/min and may miss lesions that bleed only intermittently. Long-Term MonitoringMonitor patients with iron deficiency anemia on an outpatient basis to ensure that there is an adequate response to iron therapy and that iron therapy is continued until after correction of the anemia to replenish body iron stores. Follow-up also may be important to treat any underlying cause of the iron deficiency. Response to iron therapy can be documented by an increase in reticulocytes 5-10 days after the initiation of iron therapy. The hemoglobin concentration increases by about 1 g/dL weekly until normal values are restored. These responses are blunted in the presence of sustained blood loss or coexistent factors that impair hemoglobin synthesis.
Author James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology Disclosure: Nothing to disclose. Coauthor(s) Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG Disclosure: Partner received none from No financial interests for none. Chief Editor Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences Disclosure: Nothing to disclose. Acknowledgements Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences Disclosure: Nothing to disclose. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Which condition is a common expected adverse effect of iron supplementation?The most common side effects are gastrointestinal, such as nausea/vomiting, constipation or diarrhea, flatulence, metallic taste, staining of the teeth, or epigastric distress.
When administering ferrous sulfate What is an important nursing consideration?Liquid preparations of ferrous sulfate may stain teeth. Instruct the patient to dilute liquid iron preparations with juice or water, administer through a straw, and rinse the mouth after taking the medication.
When administering ferrous sulfate iron to a patient the nurse should plan to give this medication with which fluid to increase absorption of the iron?Some doctors suggest taking a vitamin C supplement or drinking orange juice with your iron pill. This can help the iron absorb into your body. Drinking 8 ounces (240 milliliters) of fluid with an iron pill is also OK.
What is the ferrous fumarate used for?Ferrous fumarate: medicine to treat iron deficiency anaemia - NHS.
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