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continuing education for pharmacists Volume XXXI, No. 6 : Disease Basics, Treatment and Appropriate Use of ESAs

Mona T. Thompson, R.Ph., PharmD

Dr. Mona T. Thompson has no relevant considered a public health concern have an increased demand for iron. financial relationships to disclose. that affects both developed and In the United States, the preva- developing countries. Estimates lence of iron-deficiency anemia in the Americas and Europe were among children declined during the The goal of this lesson is Goal. lower than in other regions such as 1970s in association with increased to provide a basic background on Africa and Eastern Mediterranean. iron intake during infancy. It is anemia to include pathophysiol- Anemia is the result of one estimated that 4 percent of women ogy, epidemiology, and associated or more of the three independent in the United States between the laboratory studies in the diagnosis mechanisms that occur secondary ages of 20 to 49 years have iron of anemia; common types of anemia to various deficiencies and disor- deficiency anemia. According to and their causes; and treatment ders: (1) decreased red blood cell the WHO definition, more than 10 options in adults. (RBC) production, (2) increased percent of persons older than 65 RBC destruction, and (3) blood loss. years are anemic. The prevalence At the completion of Objectives. Decreased RBC production is the increases with age, and one study this activity, the participant will be result of nutrient deficiencies such found that it approaches 50 percent able to: as iron, , and ; in chronically ill patients living in 1. demonstrate an understand- bone marrow suppression (drugs, nursing homes. ing of the epidemiology, pathophys- chemotherapy, radiation); bone Table 1 lists the normal red iology, and associated laboratory marrow disorders (aplastic anemia, blood cell parameters in adults. studies in the diagnosis of anemia; myelodysplasia, tumor infiltration); Several studies have demonstrated 2. recognize the general charac- low levels of (EPO); that anemia is an independent risk teristics and causes for select types ; and other factor for increased morbidity and of anemia; chronic diseases. Iron deficiency is mortality, and decreases quality of 3. identify the general adult the cause in approximately 30 to 50 life in older persons living indepen- treatment options for anemia percent of anemia cases. Hemolyt- dently. Functional deterioration types, as well as key prescribing ic are caused by RBC de- increases with decreased hemoglo- and counseling points for the enti- struction. Examples include sickle bin concentration in an inverse and ties discussed; and cell disease and thalassemias. In linear fashion. 4. demonstrate an understand- some cases, the cause of anemia is ing of the current recommenda- unexplained. Red Blood Cells Life Cycle tions for the use of erythropoietin The WHO defines anemia as a and Function of stimulating agents (ESAs). (Hb) level less than 13 Erythropoietin grams per dL in men, and less than RBCs, also known as erythrocytes, Background 12 grams per dL in women. Other are produced through the process Anemia is one of the most com- authors have proposed different of erythropoiesis which occurs in mon hematologic problems in ranges and lower limits of normal the bone marrow. While the pro- both adults and children. In a that vary based on age, sex, and cess is dependent on various fac- prevalence study conducted us- race. Patients living at high alti- tors, erythropoietin (EPO) plays an ing data from 1993 to 2005, the tude and athletes may also have integral role. EPO is an endocrine World Health Organization (WHO) different normal values. hormone produced in the kidney reported that globally, anemia Anemia occurs at all stages by cells that sense inadequate affected 1.62 billion people, cor- of life but most often in pregnant tissue oxygenation. Once hypoxia relating to almost 25 percent of women and preschool-aged chil- is sensed, EPO is produced and the population. Therefore, it is dren, which are populations that travels to the bone marrow where microcytic anemias are iron defi- Table 1 ciency, thalassemia, and anemia of Normal Red Blood Cell Parameters for Adults chronic inflammation. Macrocytic anemias are often due to alcohol- Red Cell Parameter Men Women ism, liver disease, folic acid and Hemoglobin, g/dL 15.7 +/- 1.7 13.8 +/- 1.5 vitamin B12 deficiency. Ferritin Hematocrit, percent 46 +/- 4.0 40.0 +/- 4.0 serum levels, which measure iron RBC count, 5.2 +/- 0.7 4.6 +/- 0.5 million/µL storage in the body (but not the Reticulocytes, percent 1.6 +/- 0.5 1.4 +/- 0.5 iron contained in heme or hemo- Mean corpuscular 88.0 +/- 8.0 88.0 +/- 8.0 globin), may also be obtained with volume, fL vitamin B12 and folate levels. Peripheral blood smears entail examining a single layer of blood it augments and differentiates of breath, dizziness, coldness in microscopically, in order to study two erythroid progenitors – burst hands and feet, and chest pain are the content of the cell. A reticu- forming units-erythroid (BFU-E) common, yet nonspecific, symptoms locyte count is a blood test that and colony forming units-erythroid that are often experienced. These measures how fast red blood cells (CFU-E) – into normoblasts. Once symptoms occur due to the lack are made by the bone marrow and the normoblast loses its nucleus, it of oxygen delivery to tissue and/ released into the blood. Reticulo- is termed a reticulocyte or imma- or acute, marked bleeding caus- cyte counts usually rise secondary ture red blood cell. The reticulo- ing hypovolemia. Clinicians are to blood loss or in cases of hemolyt- cyte spends about three days in the encouraged to complete a thorough ic anemia. Additionally, a low total bone marrow, and an additional and systematic approach so as white blood cell (WBC) count in a day in peripheral blood before it is not to overlook underlying causes. patient with anemia would lead fully matured. The mature RBC Angular cheilitis (cracking at the to consideration of bone marrow circulates in the body, deliver- edges of the lips) and koilonychias suppression, whereas a high total ing oxygen linked to hemoglobin (spooning of the nails) may ac- WBC may correlate with infection, from the lungs to tissue capillar- company iron deficiency anemia. inflammation, or a hematologic ies. After 110 to 120 days, the Neurological manifestations can malignancy. RBC is removed from circulation accompany or predate anemia asso- by macrophages sensing that the ciated with vitamin B12 deficiency. cell is aged. Under steady state The patient’s past medical history Treatment of Select conditions, the rate of RBC produc- can be helpful, as can a review of Anemias The remainder of this lesson will tion equals the rate of RBC loss, pharmacologic agents since certain review iron deficiency anemia and the reticulocyte count repre- medications, especially chemother- (IDA), anemia of chronic disease sents about 1 percent (normal for apy, may be associated with bone (ACD), and anemia associated with adults is 0.5 to 2 percent) of the marrow suppression. In addition, chronic kidney disease (CKD) as total circulating RBC. The normal some medications such as NSAIDs these types of anemia are often RBC count is five million µL (5 x and anticoagulants can increase encountered in the community set- 1012/L). Therefore, the bone mar- the risk of bleeding resulting in ting. Various oral and intravenous row must produce approximately anemia secondary to blood loss. iron agents as well as erythropoi- 50,000 reticulocytes/µL of whole etin stimulating agents (ESAs) are blood each day in order to main- Laboratory Studies for prescribed for their treatment. tain stable RBC mass. Persistent Diagnosing Anemia reduced rates of production lead to This section will briefly review the anemia. The rate of red blood cell laboratory studies that a clinician Iron Deficiency Anemia Iron deficiency is the most common production greatly increases under may utilize to not only confirm a di- nutritional deficiency worldwide. the influence of high levels of EPO. agnosis of anemia, but classify the Iron metabolism is controlled by In fact, normal bone marrow can type and determine the treatment absorption rather than excretion, increase erythropoiesis in response approach. Upon confirmation of and iron is only lost through blood to EPO approximately fivefold in anemia (Hb <13g/dL in men; <12g/ loss or in RBCs as they slough. adults. dL in women according to WHO), Men and non-menstruating women a complete blood count is generally lose approximately 1mg of iron Signs and Symptoms of obtained. The mean corpuscular each day, while menstruating Anemia volume (MCV) or red blood cell size women lose 0.6 to 2.5 percent more. The signs and symptoms of anemia is used to distinguish microcytic Pregnancy requires about 700mg are dependent on the degree of ane- (MCV <80fL), normocytic (MCV 80 of iron; a complete blood donation mia, the rate at which it evolved, to 100fL), and macrocytic (>100fL) of 500mL contains 250mg of iron. and the oxygen demands of the anemias. Iron absorption occurs mostly in patient. Fatigue, pallor, shortness The most commonly seen Dietary Reference Intake (DRI) for disease, diabetes, trauma, etc. Table 2 iron is 8mg per day for healthy, ACD is generally mild, normo- Causes and Examples of non-menstruating adults, 18mg per cytic and normochromic (concen- Iron Deficiency in Adults day for menstruating women, and tration of Hb in RBC is normal). 16mg per day for vegetarians (due However, it can become microcytic Increased iron loss to the difference in absorption of and hypochromic in long-standing Acute hemorrhage non-heme iron). cases, and can be severe. Labora- Chronic or occult hemorrhage IDA is usually a microcytic tory findings usually reveal a low Menstruation Inflammation anemia. The most accurate initial reticulocyte count (<25,000/µL) Cancer diagnostic test for IDA is a serum reflecting reduced RBC produc- Vascular malformation ferritin measurement less than tion. The differential diagnosis for Hemolysis 40mcg/L. When iron deficiency ACD among other anemias can Blood donation is diagnosed and the underlying be challenging, and is most likely Decreased iron in diet cause addressed, restoration of iron when the following are present: low Vegetarian diet supply is necessary. While transfu- serum iron, normal to low serum Malnutrition sion can be considered for patients transferrin (glycoprotein that binds Dementia experiencing fatigue, dyspnea on to iron and controls the level of free Psychiatric illness Decreased iron absorption exertion, or for cardiac patients iron), normal to increased ferritin, Antacid therapy or high gastric pH with Hb less than 10g/dL, oral iron and elevated erythrocyte sedimen- Celiac disease therapy is the first line of therapy. tation rate and/or C-reactive pro- Inflammatory bowel disease tein. The last two findings indicate Partial gastrectomy Anemia of Chronic Disease systemic inflammation. Recogniz- Increased iron requirements Anemia of chronic disease (ACD) ing iron deficiency along with ACD Pregnancy is an anemia of underproduction may require additional testing, but Lactation of red blood cells. The cause of is suggested by the finding of low ACD is multi-factoral and includes serum ferritin levels. a mildly decreased life span of Optimal treatment of ACD the jejunum, the middle section erythrocytes, deregulated iron involves correction of the underly- of the small intestine, and is only absorption and transport, inhibi- ing disease process, if one can be about 5 to 10 percent of the dietary tion of hematopoiesis, and relative clearly documented. Managing intake. The absorption is also deficiency of erythropoietin. In chronic diseases will minimize somewhat regulated by the body simplified terms, researchers sug- inflammation and lessen bone as it decreases in states of overload gest that the underlying inflamma- marrow suppression. Most pa- and increases in states of depletion. tory medical condition causes the tients with mild anemia will have There are two forms of dietary release of cytokines such as inter- no symptoms; therefore, treat- iron: heme iron, which is found in leukins (IL-1 and IL-6), and tumor ment should be limited to those meat; and non-heme iron, which is necrosis factor leading to a cascade with severe, symptomatic anemia found in plant and dairy foods. The of events that alters the RBC life (Hb <10g/dL). Treatment options bioavailability and absorption of cycle and hematopoiesis process for these patients include blood non-heme iron requires acid diges- as stated above. Interestingly, it transfusions and ESAs. Transfu- tion. It is enhanced by ascorbic acid has been observed that the treat- sions provide immediate relief of and meat, while it is inhibited by ment of patients with rheumatoid symptoms, yet are associated with calcium, fiber, tea, coffee, and wine. arthritis using an anti-TNF-alpha the following risks: volume over- A large amount of iron is recycled antibody led to a reduction in IL-6 load, iron overload, infections, and daily for heme synthesis; therefore, levels and an improvement in ane- acute reactions. ESAs may be used only 1 to 2mg of (absorbed) iron is mia. In addition to IL-6, hepcidin, for the treatment of ACD in limited required to replace the iron losses. a protein generated in the liver, situations, but their use remains It is important to note that iron interferes with RBC production controversial. stores become depleted before iron by decreasing iron availability for deficiency anemia occurs. Table 2 incorporation into erythroblasts. Anemia in Chronic Kidney lists common causes of iron defi- Increased hepcidin levels have Disease ciency in adults. been documented in patients with Chronic kidney disease (CKD) The U.S. Preventive Services ACD, multiple myeloma, inflam- affects approximately 26 million Task Force recommends routine matory bowel disease, and Hodgkin adults in the U.S. and is associ- screening for iron deficiency in lymphoma. Precipitating illnesses ated with significant morbidity pregnant women. The task force to ACD include active infection, and mortality. Among the medical found insufficient evidence to rec- inflammatory condition, alcoholic problems facing this population is ommend for or against screening in liver disease, congestive heart fail- anemia with incidence increasing other asymptomatic persons. The ure, thrombosis, chronic pulmonary with declining glomerular filtra- tion. One study suggested that the anemia incidence is less than 10 Table 3 percent in CKD stage 1 and 2; 20- Common Oral Iron Salt Preparations 40 percent in CKD stage 3; 50-60 percent in CKD stage 4; and more Preparation Dose Elemental Iron Content than 70 percent in CKD stage 5. Ferrous sulfate tab 325mg 65mg Among other factors, the most well- Ferrous gluconate tab 300mg 36mg Ferrous fumarate tab 100mg 33mg known cause is inadequate EPO Ferrous sulfate elixir 220mg/5mL 44mg production. The problem can also be com- pounded by iron deficiency. The mechanism for how EPO produc- drops below 10g/dL with target Hb absorption and is recommended. tion is hindered is not fully under- level for treatment being 11 to 12g/ Phytates (bran, cereal), tannates stood; however, as renal failure dL. Treatment levels should not (tea), and phosphate-containing progresses, the contribution of EPO exceed a Hb of 13g/dL. If not al- carbonated beverages bind to iron. deficiency to anemia increases. Ad- ready present, iron deficiency often Therefore, iron salts should not be ditionally, as previously discussed, develops with ESA therapy due to given with these foods or beverag- acute and chronic inflammation im- the depletion of existing iron stores es. Other factors that limit absorp- pact CKD patients with anemia by when stimulating new RBCs. tion include medications that raise the involvement of cytokines and Iron is usually administered the gastric pH such as antacids, hepcidin. RBCs have a decreased orally in patients on peritoneal proton pump inhibitors, and hista- life span, and uremic toxins are dialysis, but not in patients on mine blockers. Certain antibiotics thought to contribute to apoptosis hemodialysis. Hemodialysis pa- (quinolones and tetracyclines) also (programmed cell death) in the de- tients, and those unable to respond bind to iron. Ideally, iron should velopment of RBCs. Studies have to oral supplements, will require be taken two hours before or four demonstrated an improvement in intravenous iron therapy. Despite hours after the ingestion of antac- Hb levels and decreased ESA use adequate dosing of ESAs and iron ids, quinolones and tetracyclines. with increased adequacy of dialysis therapy, patients may still require Multivitamins should never be (which removes the toxins). It has blood transfusions depending on used as the sole supplement for been hypothesized that one of the symptoms. IDA, since calcium, phosphate, and molecules in uremia is involved in magnesium found in the tablet can bone marrow suppression. Iron Treatment alter absorption. The National Kidney Founda- The three most common salts The recommended oral daily tion (NKF) Kidney Disease Out- found in oral iron preparations are dose for the treatment of IDA in comes Quality Initiative’s (KDOQI) ferrous sulfate, ferrous gluconate, adults ranges from 150 to 200mg of clinical practice guidelines and and ferrous fumarate. Oral iron elemental iron. A common starting clinical practice recommendations is available as non-enteric coated regimen is ferrous sulfate tablets advocate annual screening for tablets, enteric coated tablets, 325mg, three times a day. This anemia in all patients with CKD. prolonged release formulations, or yields an oral dose of 195mg of Most of the anemic patients with elixirs. Table 3 lists the elemental elemental iron each day. Using the CKD will have erythropoietin defi- iron content of common iron salt assumption that 10 percent of the ciency which is a diagnosis of exclu- tablet preparations. iron is absorbed, hemoglobin may sion. Many of these patients will Non-enteric coated iron tablets correct in four weeks in patients also have coexisting iron deficiency. are the most commonly used agents with moderate, uncomplicated ane- Iron deficiency is almost always because of their low cost and effec- mia. The duration of therapy varies present in hemodialysis patients tiveness. Delayed-release and en- as some experts recommend con- due to bleeding when needles are teric coated preparations are often tinuing iron therapy for six months removed from vascular access, promoted because they have better after hemoglobin is restored so that blood infiltration of the vascular gastrointestinal tolerance. How- iron stores are replenished. Others access, vascular access procedures, ever, they are not recommended for stop therapy upon Hb restoration, frequent blood testing, and clotting initial therapy as they contain less and assess for repeated anemia or general blood loss in the extra- iron and are released further down alerting the patient and physician corporeal circuit. Iron deficiency in in the intestinal tract leading to to determine the cause of iron defi- patients not yet on hemodialysis is decreased absorption. ciency. Patients predicted to have likely due to dietary protein restric- Many factors alter the absorp- ongoing iron deficits may require tion or decreased appetite for red tion of iron. Iron is best absorbed individualized maintenance dosing. meat. According to the NKF/KDO- in a mildly acidic medium. Hence, Dose dependent gastrointesti- QI guidelines, ESA therapy should the co-administration of ascorbic nal symptoms, such as abdominal be initiated when the patient’s Hb acid 250mg improves the degree of discomfort, nausea, vomiting, diar- rhea, and constipation, are com- iron present in the preparation. gic events per one million doses per mon and occur in up to 20 percent High molecular weight products year. of patients. Changing the iron salt are associated with a considerably Iron (Venofer®) is ap- and formulation are commonly higher incidence of adverse events proved for IV use only and appears tried; however, these involve dose than the low molecular weight to be safe even in patients with a reductions leading to extended product. Local reactions include prior history of sensitivity to iron treatment duration. Ferrous sul- pain, muscle atrophy, and phle- . It is indicated for the fate elixir is an option for patients bitis. Systemic reactions include treatment of iron-deficiency ane- with persistent gastric intolerance. fever, urticaria, and a flare in ar- mia in CKD, including non-dialysis It allows the dose to be titrated up thritis in patients with rheumatoid dependent patients (with or with- or down until it is tolerated by the arthritis. out ESAs) and dialysis-dependent patient. While absorption will be Patients receiving iron dex- patients receiving ESA therapy. It affected, taking iron salts with food tran for the first time must receive may be used off-label for cancer- or may alleviate symptoms. Laxa- a 0.5mL test dose given by slow chemotherapy-associated anemia. tives, stool softeners, and adequate IV push over five minutes. The Dosing varies by indication, but is intake of liquids may also reduce remainder of the dose, which is generally either 100mg or 200mg constipation. calculated and individualized for per infusion with a cumulative dose Indications for intravenous the patient based on Hb, may be of 1000mg. It may be given slow iron include chronic uncorrectable administered following a one-hour IV push over two to five minutes, bleeding, intestinal malabsorption, observation period. Fatal reactions or diluted in normal saline for a and intolerance to oral iron. As have occurred, even in patients slower infusion. Adverse reac- previously discussed, intravenous who tolerated the test dose. It may tions include hypotension (up to 39 iron is commonly used in hemodi- be administered by IV bolus at a percent in hemodialysis patients), alysis patients. It is important to rate of <50mg/minute or diluted peripheral edema, headache, diar- state that the hematologic response in 250 to 1000mL of normal saline rhea, nausea, vomiting, and muscle to parenteral iron treatment is not over one to six hours. Subsequent cramps (29 percent in hemodialysis faster than that of oral therapy. doses do not require a test dose. patients). Life-threatening reac- Hypersensitivity reactions While it may be given IM, IV is the tions, including anaphylaxis, may have been reported with all of the preferred route. IM administration occur in fewer than 1 percent of intravenous iron products. Patients has not been shown to be safer or patients. Product labeling does not should be closely monitored during less toxic, and may be associated indicate the need for a test dose in administration and for at least 30 with bruising due to repeated injec- product-naïve patients, but a test minutes following administration tions and variable absorption. Iron dose is strongly recommended in of the iron preparation. Deaths dextran complex use has decreased patients who are sensitive to iron have been reported following ana- since the introduction of other dextran or have other drug aller- phylactic-type reactions; therefore, intravenous iron preparations as- gies. these agents should only be used sociated with fewer adverse events. Ferumoxytol (Feraheme®) where resuscitation equipment and Ferric gluconate complex is approved for the treatment of personnel are available. (Ferrlecit®) is approved for the IDA in adult patients with chronic At the time of writing this les- treatment of iron deficiency anemia kidney disease. It is administered son, there were four intravenous in patients with CKD who are un- as a 510mg intravenous dose at preparations available in the U.S. dergoing hemodialysis and receiv- a rate of 30mg/second as a single which are described briefly. Refer ing ESAs. Off-label use includes dose, followed by a second 510mg to product labeling for full prescrib- cancer-/chemotherapy-associated dose three to eight days later. A ing information. anemia. It is dosed as 125mg test dose is not required, however, Iron dextran complex con- undiluted by slow IV push at a rate patients should be monitored tains 50mg of elemental iron per of 12.5mg/min or diluted in 100mL during and for 30 minutes, or mL and can be given IM or IV. It of normal saline and infused over until clinically stable, following is indicated for IDA in patients in 30 to 60 minutes. The dose may be administration. Anaphylactic-type whom oral iron is not feasible or in- repeated up to a cumulative dose reactions presenting with cardiac/ effective. INFeD® and Dexferrum® of 1000mg. A 2mL test dose was cardiorespiratory arrest, clinically are two brands of iron dextran, but previously recommended, but is significant hypotension, syncope, differ in that they are low and high not in current manufacturer label- and unresponsiveness have been molecular weight preparations, ing. Doses greater than 125mg are reported in post-marketing expe- respectively. Anaphylactic reac- associated with increased adverse rience. Feraheme may interfere tions occur in about 1 percent of events. Data indicates that, in com- with MRI imaging for up to three patients with either the low or high parison to iron dextran, Ferrlecit months after the last dose. molecular weight products, and are use results in 3.3 versus 8.7 aller thought to be caused by the free ESA to another. The author, the Ohio Pharmacists Founda- Table 4 The use of these agents has tion and the Ohio Pharmacists Association Guidelines for Use of ESAs reduced the need for RBC transfu- disclaim any liability to you or your patients in Patients with Anemia resulting from reliance solely upon the infor- sions, but their use is not without mation contained herein. Bibliography for risk. All three product labels carry additional reading and inquiry is available Indications approved by FDA similar black box warnings regard- upon request. Epogen/Procrit ing greater risk for death, serious Treatment of anemia This lesson is a knowledge-based CE activity and - due to Chronic Kidney Disease adverse cardiovascular reactions, is targeted to pharmacists in all practice settings. (CKD) in patients on dialysis and and stroke when the ESA is admin- not on dialysis. istered to target a Hb level greater than 11g/dL. Possible causes in- - secondary to Zidovudine use in Program 0129-0000-13-006-H01-P HIV-infected patients. clude complete and/or too rapid cor- Release date: 6-15-13 - due to the effects of concomitant rection of anemia that can increase Expiration date: 6-15-16 myelosuppressive chemotherapy, blood pressure and the risk of CE Hours: 1.5 (0.15 CEU) and upon initiation, there is a thrombosis, by accentuating vaso- minimum of two additional constriction and increasing platelet months of planned chemotherapy. adhesiveness and blood viscosity. The Ohio Pharmacists Foundation Inc. is Aranesp accredited by the Accreditation Council Treatment of anemia due to All of the agents are contraindi- for Pharmacy Education as a provider of continuing pharmacy education. - Chronic Kidney Disease (CKD) in cated in uncontrolled hypertension. patients on dialysis and patients Additional warnings and prescrib- not on dialysis. ing restrictions are included for - the effects of concomitant myelo- ESAs that are approved for use in suppressive chemotherapy, and patients in treating anemia due to upon initiation, there is a mini- myelosuppressive chemotherapy. mum of two additional months of Clinicians are reminded to use planned chemotherapy. the lowest ESA dose sufficient to reduce the need for RBC transfu- sions. In terms of efficacy, epoetin Erythropoietin alfa and darbepoetin are widely Stimulating Agents considered equal when dosed ac- ESAs are used to prevent the need cordingly. ESA doses should be for RBC transfusions. They have individualized based on causes of not been shown to improve qual- anemia and symptoms. ity of life, fatigue or patient well- being. ESAs stimulate erythropoi- Summary esis through the same process as Iron deficiency anemia, anemia of endogenous EPO. Increases in Hb chronic disease, and anemia due to levels are generally seen two to six chronic kidney disease are among weeks after administration. During the most common types of anemia. treatment with ESAs, iron reple- Anemia can have a profound effect tion must be maintained to ensure on quality of life with symptoms effectiveness. including fatigue, dizziness, short- Currently there are three ESAs ness of breath, and decreased sense available in the U.S. Epoetin alfa, of well being. Complications of the first ESA available, was mar- anemia include reduced cognitive keted as Epogen® and Procrit® in function and mental acuity, im- 1989. (Aranesp®) paired quality of life, and the need was introduced in 2001. Most for blood transfusions. Untreated recently, (Omontys®), anemias can lead to cardiovas- a synthetic peptide analog of EPO, cular disease with left ventricu- was approved in 2012, and volun- lar hypertrophy and congestive tarily recalled in February 2013. heart failure, or worsen existing Table 4 summarizes the FDA-ap- heart disease. Anemia may also proved indications for these prod- be responsible for declining renal ucts. Refer to product information function in some groups. Oral and for approved indications, dosing, parenteral iron supplements, as monitoring, subsequent dosing ad- well as ESAs, are available treat- justments, and information regard- ment options. Iron must be admin- ing converting patients from one istered with ESA therapy to avoid depletion. Please print. Program 0129-0000-13-006-H01-P continuing education quiz 0.15 CEU Name______

Address______Anemia: Disease Basics, Treatment and Appropriate Use of ESAs City, State, Zip______Email______1. An example of hemolytic anemia caused by red blood cell destruction is: NABP e-Profile ID*______a. iron deficiency. c. chronic kidney disease. *Obtain NABP e-Profile number at www.MyCPEmonitor.net. b. folate deficiency. d. sickle cell disease. Birthdate______(MMDD) Return quiz and payment (check or money order) to 2. Anemia occurs most often in all of the following EX- Correspondence Course, OPA, CEPT: 2674 Federated Blvd, Columbus, OH 43235-4990 a. pregnant women. b. preschool aged children. c. newborns. 8. Recognizing iron deficiency along with ACD is sug- gested by the finding of low: 3. Erythropoiesis occurs in the bone marrow. a. sedimentation rate. a. True b. False b. serum iron levels.

c. serum ferritin levels. 4. All of the following symptoms are common in anemia

EXCEPT: 9. The National Kidney Foundation Kidney Disease a. fatigue. c. headache. Outcomes Quality Initiative recommends screening for b. pallor. d. shortness of breath. anemia in all patients with CKD: a. only at diagnosis. c. biannually. 5. Macrocytic anemias are often due to all of the follow- b. annually. d. every five years. ing EXCEPT: a. alcoholism. c. liver disease. 10. The oral iron salt containing the highest amount of b. thalassemia. d. vitamin B12 deficiency. elemental iron is: a. ferrous sulfate. 6. Iron absorption occurs mostly in the: b. ferrous gluconate. a. cecum. c. ileum. c. ferrous fumarate. b. duodenum. d. jejunum.

11. Iron is best absorbed in a mildly: 7. Iron deficiency anemia is usually a: a. basic medium. b. acidic medium. a. microcytic anemia. b. macrocytic anemia. 12. The preferred route of administration for iron dex- c. normocytic anemia tran complex is:

a. intravenous. b. intramuscular.

13. Which of the following requires a test dose prior to administration? Completely fill in the lettered box corresponding to a. Ferumoxytol c. Iron dextran complex b. Iron sucrose d. Ferric gluconate complex your answer. 1. [a] [b] [c] [d] 6. [a] [b] [c] [d] 11. [a] [b] 14. All ESA products carry a black box warning regard- 2. [a] [b] [c] 7. [a] [b] [c] 12. [a] [b] ing greater risk of all of the following EXCEPT: 3. [a] [b] 8. [a] [b] [c] 13. [a] [b] [c] [d] a. stroke. c. serious cardiovascular reactions. 4. [a] [b] [c] [d] 9. [a] [b] [c] [d] 14. [a] [b] [c] [d] b. death. d. serious hypersensitivity reactions. 5. [a] [b] [c] [d] 10. [a] [b] [c] 15. [a] [b] [c]

 I am enclosing $10 (member); $15 (non member) for 15. All erythropoietin stimulating agents are contraindi- this month’s quiz made payable to: Ohio Pharmacists cated in: Association. a. HIV infection. b. rheumatoid arthritis. 1. Rate this lesson: (Excellent) 5 4 3 2 1 (Poor) c. uncontrolled hypertension. 2. Did it meet each of its objectives?  yes  no If no, list any unmet______3. Was the content balanced and without commercial bias?  yes  no 4. Did the program meet your educational/practice needs? To receive CE credit, your quiz must be received no later than June 15,  yes  no 2016. A passing grade of 80% must be attained. All quizzes received 5. How long did it take you to read this lesson and complete the after July 1, 2012 will be uploaded to the CPE Monitor and a state- quiz? ______ment of credit will not be mailed. Send inquiries to 6. Comments/future topics welcome. [email protected]. june 2013