University Health System Pharmacy & Therapeutics Committee Iron sucrose (Venofer®) Guidelines for Use October 2010

OVERVIEW ALTERNATIVE USAGE AND DOSING • Iron sucrose (Venofer®) is an intravenous iron supplement used to replete • Use in chemotherapy‐related anemia: The use of intravenous iron iron stores in patients with chronic kidney disease (CKD) supplementation may decrease red blood cell (RBC) transfusion • It has been shown to be effective in hemodialysis‐dependent (HDD), requirements greater than oral iron therapy in patients with anemia related nonhemodialysis‐dependent (NDD), and peritoneal dialysis (PDD) patients to chemotherapy.2 • Intravenous (IV) administration overcomes issues related to oral iron • Higher doses of iron sucrose: Doses of 300 mg given over 2 hours appear to supplementation be safe and well‐tolerated.3 Doses of 400‐ 500 mg diluted in 250 mL of o Multiple daily dosing normal saline given in a single infusion over 2‐3 hours on days 1 and 14 has 4,5 o Inadequate absorption been studied for iron‐repletion in HDD‐CKD and NDD‐CKD patients. o Gastrointestinal side effects (nausea, constipation) Adverse events were more common at higher doses. Hypotension may be • Its use is favored to other IV formulations such as iron dextran due to a more frequent in patients receiving larger doses during hemodialysis. decreased incidence of hypersensitivity reaction Higher doses of iron sucrose may be better tolerated in patients not on 4,5 o Administration of a test dose of iron sucrose is not required1 hemodialysis. • Not indicated for total dose infusions CONTRAINDICATIONS • ALL PATIENTS ON ERYTHROPOIETIN THERAPY SHOULD BE GIVEN • Iron overload SUPPLEMENTAL IRON • Known hypersensitivity to any component of the formulation FDA‐APPROVED USES • Anemia not caused by iron deficiency • Iron deficiency anemia WARNINGS o All NDD‐CKD patients • Hypersensitivity reaction o HDD‐CKD patients receiving concurrent erythropoietin therapy o Monitor for signs and symptoms of an allergic reaction during infusion o PDD‐CKD patients receiving concurrent erythropoietin therapy o Patients with pre‐existing immune‐mediated diseases may be at FDA‐APPROVED DOSING increased risk • Total cumulative iron dose of 1,000 mg is generally sufficient to replete iron • Hypotension stores in patients with CKD o May be related to the rate of administration and total amount of drug • HDD‐CKD1 administered o 100 mg undiluted injection, given over 2‐5 minutes OR P&T GUIDELINES FOR USE o 100 mg in 100 mL of normal saline, given over 15 minutes • Iron sucrose should only be used in the following patient populations: o Give with each hemodialysis session until total cumulative iron dose is o Patients with iron deficiency anemia due to CKD met o Patients with chemotherapy‐induced anemia • NDD‐CKD1 o Patients with active bleeding who refuse blood transfusion o 200 mg undiluted injection, given over 2‐5 minutes P&T RESTRICTIONS o Give total cumulative iron dose in 5 separate administrations within As of October 2010, the use of iron sucrose is no longer restricted. 14 day period

Table 1: Comparison of IV iron products Formulation Concentration Advantages Disadvantages Incidence of Reported hypersensitivity In‐patient cost of elemental adverse events6 (per 1 million doses)6 iron Can be administered to iron dextran‐sensitive patients6 Free‐iron toxicity: nausea, vomiting, flushing, and hypotension with rapid $40.57/100 mg Decreased risk of free iron or large dose administration Iron sucrose 20 mg/mL remaining in circulation Up to 36% 2.6 (Venofer®) No total dose iron replacement‐ must

Larger doses (200‐300 mg) be given 1‐3 times per week given over 2 hours appear to be well tolerated3,5 Free‐iron toxicity: nausea, vomiting, flushing, and hypotension with rapid or large dose administration

Can be administered to iron Sodium ferric Increased free iron in circulation due $43.52/125 mg dextran‐sensitive patients6 gluconate 12.5 mg/mL to rapid release of iron from gluconate Up to 35% 3.3

(Ferrlecit®) complex6

No total dose iron replacement‐ given over 8 separate dialysis sessions

Only IV iron product approved Highest rate of adverse events, for total dose infusion including hypersensitivity reactions 8.7* Dexferrum®:

Can be given IM $21.50/100 mg Iron dextran Hypersensitivity reaction caused by *Adverse events are more (Dexferrum®, 50 mg/mL antigenicity of dextran component Up to 50% Adverse events are not related common with high‐ INFeD®: $23.02/100 Infed®) to the rate of administration‐ molecular weight iron mg Requires administration of a 25 mg iron dextran complex dextran (Dexferrum®) test dose dissociates slowly

References 1. Venofer® package insert. American regent; last revision 10/08. 2. Dangsuwan P, Manchana T. Blood transfusion reduction with intravenous iron in gynecologic cancer patients receiving chemotherapy. Gynecologic Oncology 2010; 116: 522‐525. 3. Hollands J, Foote E, Rodriguez A. Safety of high‐dose iron sucrose infusion in hospitalized patients with chronic kidney disease. Am J Health‐Syst Pharm 2006;63:731‐735. 4. Chandler G, Harchowel J, Macdougall I. Intravenous iron sucrose: establishing a safe dose. Am J Kid Dis 2001; 38 988‐991. 5. Blaustein D et al. The safety and efficacy of an accelerated iron sucrose dosing regimen in patients with chronic kidney disease. Kid Inter 2003;64:S72‐S77. 6. Silverstein S, Rodgers G. Parenteral iron therapy options. Am J Hematol 2004;76:74‐78. 7. Sinha S, Chiu D, Kolakkat S. Comparison of intravenous iron sucrose versus low‐molecular‐weight iron dextran in chronic kidney disease. J Renal Care 2009;35:67‐73.