Intravenous Iron: A Good Thing Made Better? Marilyn Telen, MD Wellcome Professor of Medicine Duke University
Use of IV Iron There are increasing data regarding safety of IV iron. IV iron is superior to oral iron in both CKD and cancer. IV iron is efficacious in many other clinical settings. There are now 4 formulations that allow complete replacement of iron in 1 to 2 administration sessions. IV iron should be a key part of the repertoire of every practicing hematologist. (Auerbach & Deloughery, Hematology 2016)
Iron Deficiency Causes and Effects Bleeding and pregnancy are most common in adults. Malabsorption: bariatric surgery, atrophic gastritis, and inflammatory bowel disease In adults, bleeding must have its cause identified (colon or other GI malignancy unless proven otherwise). In addition to anemia, ID causes decrements in energy, activity, quality of life, cognitive function, sexual function, and work productivity.
Diagnosis of Iron Deficiency Anemia, with microcytosis, hypochromia, low MCH and MCHC, low RBC count, and high RDW In elderly patients, B12 deficiency and iron deficiency may present together due to atrophic gastritis and malabsorption Always confirm the presence of true iron deficiency with laboratory tests: Fe, TIBC, % transferrin saturation Ferritin Soluble (serum) transferrin receptor level (stfr) if interpretation of the above results is difficult Iron deficiency is usually hypoproliferative and thus is accompanied by a low reticulocyte count. Avoid giving IV iron to someone with microcytic anemia due to a thalassemia syndrome!
Correct anemia Goals of Therapy Replete iron stores (ferritin of 100 ng/ml or greater) Correct other symptoms of iron deficiency Total iron deficit (Ganzoni s Formula) = Body weight [kg] x (Target Hb - Actual Hb) [g/dl] x 2.4 + 500mg (if body weight >35kg) On line calculators available, such as: http://www.gastrotraining.com/calculators/ironreplacement-parenteral-dosing-for-iron-deficiency
Indications for IV Iron 1. Iron deficiency anemia in which oral iron Is not tolerated Is not efficacious 2. Hemodialysis-dependent ESRD with iron deficiency 3. Cancer with iron deficiency 4. New and possibly forthcoming indications Iron deficiency during pregnancy Bariatric surgery Post-operative iron deficiency Restless leg syndrome Altitude sickness prophylaxis
Indications for IV Iron: Medicaid All indications approved by the Food and Drug Administration (FDA) are covered unless otherwise specified. FDA-approved Indication: Iron deficiency anemia in patients in whom a trial period of oral iron was documented ineffective or infeasible. Some formulations are FDAapproved only in certain clinical settings. Off-label uses of an approved drug may be covered if the data on drug use are consistent with the compendia and peer-reviewed medical literature, according to 42 U.S.C. 1396r-8(g)(1)(B), and as determined by NC Division of Medical Assistance (DMA).
Medicaid: Additional Indications for IV Iron Iron deficiency anemia in hemodialysis-dependent chronic kidney disease Hemodialysis-dependent chronic kidney disease with epoetin therapy Iron deficiency anemia in peritoneal dialysis-dependent chronic kidney disease Peritoneal dialysis-dependent chronic kidney disease with epoetin therapy; Iron deficiency anemia in non dialysis dependent chronic kidney disease; Non-dialysis dependent chronic kidney disease with or without epoetin therapy Iron deficiency anemia from excessive uterine blood loss or pregnancy Iron deficiency anemia of cancer and cancer chemotherapy Iron deficiency anemia with comorbid heart failure Iron repletion for autologous blood transfusions Gastrointestinal (GI) blood loss with iron deficiency Disorders of iron adsorption or metabolism, including iron deficiency where oral treatment is ineffective or infeasible
IV Iron in Dialysis-Dependent CKD Iron deficiency is common in patients on chronic dialysis, and most require iron-replacement therapy. Both absolute and functional iron-deficiency anemia have been shown to respond to intravenous (IV) iron replacement. IV iron is superior to oral iron in patients on hemodialysis. Limited trial and observational data suggest that a maintenance dosing regimen may be more efficacious and possibly safer than loading therapy. However, in DEcIDE, maintenance IV iron was associated with reduced epo utilization and improved early survival but not with the improveed achievement of Hb targets (10-12 g/dl). Michels WM et al. (DEcIDE). Nephrol Dial Transplant. 2016 Pandey R et al. Semin Nephrol. 2016
Post-Operative Anemia IV iron (ferric carboxymaltose) produced significant improvements vs placebo in primary outcome measures: Hemoglobin concentrations Iron stores, Need for blood transfusion Secondary outcome measures were also improved, including Postoperative length of hospital stay Occurrence of postoperative infection Quality of life. Khalafallah et al. Lancet Haematol 2016.
IV Iron in Cancer Steinmetz et al. Ann Oncol. 2013
IV Iron in CHF: The FAIR-HF Trial Ferric carboxymaltose vs placebo in 459 pts with CHF and Fe deficiency. Mean Hb both groups was 11.9 g/dl. The dose needed to correct iron deficiency was calculated according to Ganzoni s formula and was provided over a period between 3 and 7 weeks (a median of six injections) during the correction phase. Anker et al. NEJM, 2009
IV Iron in CHF: The FAIR-HF Trial IV Fe was significantly associated with improved symptoms, functional capacity, and quality of life. IV Fe was not associated with an unacceptable sideeffect or adverse-event profile. Anker et al. NEJM, 2009
How Dangerous is IV Iron? 2010 2015: 30 patients identified from FDA Adverse Event Reporting System Search as having developed fatal anaphylaxis. However, when HMWID was avoided, the incidence of serious adverse events with IV iron in >30 million doses were extremely rare, with an estimated incidence of 1:200,000 doses. McCulley et al. Am J Hemat. 2016 Chertow et al. Nephrol Dial Transplant. 2006.
Available IV Iron Preparations Chemical name Brand Name LMW Iron Dextran Ferric Gluconate Iron Sucrose Ferumoxytol INFeD Ferrlicit Venofer Feraheme Mol. Weight 165,000 289,000 444,000 34,000 60,000 750,000 [Iron] mg/ml 50 12.5 20 30 Vial volume 2 5 5 17 (ml) Approved dose (mg) 25 mg test dose, then100 mg or total dose required 125 mg/dose with dialysis and epo 200 mg x 5 or 500 mg x 2 510 mg x 1 and again in 3-8 days
Risk of Fatal Anaphylaxis on Day of Intravenous Iron Administration Auerbach & Adamson. Am J Hemat. 2016
SAEs Against All Other Comparators Auerbach & Deloughery. Hematology 2016
SAEs with Available IV Iron Preparations McCulley et al. Am J Hemat. 2016
Take Home Message(s) IV iron is safe. Iron stores can be repleted in 1 2 infusions, at least with some preparations. The risks of different iron preparations do not seem significantly different, although some have theoretical benefits related to release of free iron. IV iron works better than oral iron in certain circumstances, such as ESRD, cancer, CHF, and s/p bariatric surgery. Iron repletion has multiple health benefits beyond improvement of anemia.