Iron Dextran

1 INDICATIONS AND USAGE INFeD is indicated for treatment of adult and pediatric patients of age 4 months and older with documented iron deficiency who have intolerance to oral iron or have had an unsatisfactory response to oral iron. INFeD, an iron replacement product, is indicated for treatment of adult and pediatric patients of age 4 months and older with documented iron deficiency who have intolerance to oral iron or an unsatisfactory response to oral iron. ( 1 )

2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for weight-based dosing and administration information. ( 2 ) Weight in Kg Weight in Kg INFeD dose volume 2.1 Important Pre-Treatment Information Discontinue administration of any iron-containing products prior to administration of INFeD. Assess baseline hematologic (hemoglobin and hematocrit) and iron storage parameters (serum iron, total iron binding capacity, and percent saturation of transferrin) to monitor response to therapy. Administer a test dose of INFeD prior to administration of therapeutic dose [see Dosage and Administration ( 2.4 )] . 2. 2 Recommended Dosage for Iron Deficiency Anemia Calculate the INFeD dose based upon Table 1 and formulas below. Continue INFeD until hemoglobin is within the normal range and iron stores are replete. Administer daily doses of no more than 2 mL of INFeD until the total required dose is administered. Monitor response to therapy by evaluating hematologic parameters (hemoglobin and hematocrit) and iron storage parameters (serum iron, total iron binding capacity, and percent saturation of transferrin). Iron storage parameters may improve prior to hematologic parameters. Serum ferritin may not be an accurate measure of body iron stores in patients on chronic dialysis. Table 1: Total INFeD Requirement for Hemoglobin Restoration and Iron Stores Replacement in Patients with Iron Deficiency Anemia* P A T I E N T LE A N BODY WE I GHT Recommended Volume (mL) o f I N FeD B a s ed o n O b s e r v ed H e m o g lobi n kg lb 3 (g/d L ) 4 (g/d L ) 5 (g/d L ) 6 (g/d L ) 7 (g/d L ) 8 (g/d L ) 9 (g/d L ) 10 (g/d L ) 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 11 22 33 44 55 66 77 88 99 110 121 132 143 154 165 176 187 198 209 220 231 242 253 264 3 7 10 16 20 23 27 31 35 39 43 47 51 55 59 63 66 70 74 78 82 86 90 94 3 6 9 15 18 22 26 29 33 37 41 44 48 52 55 59 63 66 70 74 77 81 85 88 3 6 9 14 17 21 24 28 31 35 38 42 45 49 52 55 59 62 66 69 73 76 80 83 3 5 8 13 16 19 23 26 29 32 36 39 42 45 49 52 55 58 62 65 68 71 75 78 2 5 7 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 67 70 73 2 4 7 11 14 17 20 22 25 28 31 34 36 39 42 45 48 50 53 56 59 62 64 67 2 4 6 10 13 15 18 21 23 26 28 31 34 36 39 41 44 46 49 52 54 57 59 62 2 3 5 9 12 14 17 19 21 24 26 28 31 33 35 38 40 42 45 47 50 52 54 57 *Table values were calculated based on a normal adult hemoglobin of 14.8 g/dL for patients with body weights greater than 15 kg (33 lbs) and a hemoglobin of 12 g/dL for patients with body weights less than or equal to 15 kg (33 lbs). Alternatively, the total dose may be calculated using the formulas below: Adults and Children over 15 kg (33 lbs) Dose (mL) = 0.0442 (Desired Hb - Observed Hb) x LBW + (0.26 x LBW) Based on: • Desired Hb = the target hemoglobin in g/dL [Normal hemoglobin (males and females) for body weight over 15 kg (33 lbs) is 14.8 g/dL.] • Observed Hb = the patient’s current hemoglobin in g/dL • LBW = Lean body weight in kg [A patient’s lean body weight (or actual body weight if less than lean body weight) should be utilized when determining dosage.] • For males: LBW = 50 kg + 2.3 kg for each inch of patient’s height over 5 feet • For females: LBW = 45.5 kg + 2.3 kg for each inch of patient’s height over 5 feet • To calculate a patient's weight in kg when lbs are known: Children 5 to 15 kg (11 to 33 lbs) Otherwise, the total dose may be calculated using the formula below: Dose (mL) = 0.0442 (Desired Hb - Observed Hb) x W + (0.26 x W) Based on: • Desired Hb = the target hemoglobin in g/dL [Normal hemoglobin for children with body weight of 15 kg (33 lbs) or less is 12 g/dL.] • W = body weight in kg • To calculate a patient's weight in kg when lbs are known: 2. 3 Recommended Dosage of Iron Replacement for Blood Loss Calculate the INFeD dose based upon the formula below which is based upon the approximate amount of blood loss and pretreatment hematocrit. The formula is based on the approximation that 1 mL of normocytic, normochromic red cells contains 1 mg of elemental iron. INFeD Dose (in mL) = [Blood loss (in mL) x hematocrit] ÷ 50 mg/mL Example: Blood loss of 500 mL with 20% hematocrit Replacement Iron = 500 x 0.20 = 100 mg INFeD dose volume = 2. 4 Administration The total volume of INFeD required for the treatment of iron deficiency anemia is determined from Table 1 or the appropriate formula listed [ s ee Dosage and Administration ( 2.2 )] . The total volume of INFeD required for the treatment of iron replacement for blood loss is determined from an appropriate formula listed [ s ee Dosage and Administration ( 2.3 )] . NOTE: Do not mix INFeD with other medications or add to parenteral nutrition solutions for intravenous infusion. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit. Discard unused portion. Intravenous Injection Test Dose Prior to the first intravenous INFeD therapeutic dose, administer an intravenous test dose of 0.5 mL [see Boxed Warning and Warnings and Precautions ( 5.1 )] . Administer the test dose at a gradual rate over at least 30 seconds. Delay administration of the initial therapeutic INFeD dose until 1 hour or more after the test dose. If a hypersensitivity reaction occurs with the test dose, manage medically and do not administer further doses of INFeD. INFeD is given undiluted at a slow gradual rate not to exceed 50 mg (1 mL) per minute. The maximum daily dose of INFeD should not exceed 2 mL. Intramuscular Injection Test Dose Prior to the first intramuscular INFeD therapeutic dose, administer an intramuscular test dose of 0.5 mL [see Boxed Warning and Warnings and Precautions ( 5.1 )]. Administer the test dose at a gradual rate over at least 30 seconds into the buttock. Delay administration of the initial therapeutic INFeD dose until 1 hour or more after the test dose. If a hypersensitivity reaction occurs with the test dose, manage medically and do not administer further doses of INFeD. If no adverse reactions are observed, INFeD can be given according to the following schedule until the calculated total required dose has been reached. Each day’s dose should not exceed 0.5 mL (25 mg of iron) for infants with body weight under 5 kg (11 lbs); 1 mL (50 mg of iron) for children with body weight under 10 kg (22 lbs); and 2 mL (100 mg of iron) for other patients. The maximum daily dose of INFeD should not exceed 2 mL. INFeD should be injected only into the muscle mass of the upper outer quadrant of the buttock - never into the arm or other exposed areas - and should be injected deeply, with a 2-inch or 3-inch 19 or 20 gauge needle. If the patient is standing, he/she should be bearing his/her weight on the leg opposite the injection site, or if in bed, he/she should be in the lateral position with injection site uppermost. To avoid injection or leakage into the subcutaneous tissue, a Z-track technique (displacement of the skin laterally prior to injection) is recommended.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Delayed Reactions [see Warnings and Precautions ( 5.2 )] Increased Risk of Toxicity in Patients with Underlying Conditions [see Warnings and Precautions ( 5.3 )] Iron Overload [see Warnings and Precautions ( 5.4 ) ] Fetal bradycardia [see Use in Specific Populations ( 8.1 )] The following adverse reactions associated with the use of INFeD were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders : Leukocytosis, lymphadenopathy. Gastrointestinal disorders : Abdominal pain, nausea, vomiting, diarrhea. General disorders and administration site conditions : chest pain, chest tightness, weakness, malaise, febrile episodes, chills, shivering, sterile abscess, atrophy/fibrosis (intramuscular injection site), brown skin and/or underlying tissue discoloration (staining), soreness or pain at or near intramuscular injection sites, swelling, inflammation. Musculoskeletal and connective tissue disorders : Arthralgia, arthritis (may represent reactivation in patients with quiescent rheumatoid arthritis – [ s ee Warnings and Precautions ( 5.3 ) ] , myalgia, backache. Ne rvous system disorders : Convulsions, seizures, syncope, headache, unresponsiveness, paresthesia, dizziness, numbness, unconsciousness, altered taste. P sy chiatric disorders : Disorientation Respiratory , thoracic and mediastinal disorders : Respiratory arrest, dyspnea, bronchospasm, wheezing. Renal and urinary disorders : Hematuria. Skin and subcutaneous disorders : Urticaria, pruritus, purpura, rash, sweating. Cardiovascular disorders : Cardiac arrest, tachycardia, bradycardia, arrhythmias, acute myocardial ischemia with or without myocardial infarction or with in-stent thrombosis in the context of a hypersensitivity reaction, cyanosis, shock, hypertension, hypotension, flushing (flushing and hypotension may occur from too rapid injections by the intravenous route), local phlebitis at or near intravenous injection site. Most common adverse reactions are nausea, vomiting, chest pain, backache, hypersensitivity, dyspnea, hypotension, pruritus, flushing, dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

12.3 Pharmacokinetics Following intramuscular injection, INFeD is absorbed within 72 hours with any remaining iron absorbed over the ensuing 3 to 4 weeks. Various studies involving intravenously administered 59 Fe iron dextran to iron deficient subjects, some of whom had coexisting disease, have yielded half-life values ranging from 5 hours to more than 20 hours. The 5 hour value was determined for 59 Fe iron dextran from a study that used laboratory methods to separate the circulating 59 Fe iron dextran from the transferrin bound 59 Fe. The 20 hour value reflects a half-life determined by measuring total 59 Fe, both circulating and bound. It should be understood that these half-life values do not represent clearance of iron from the body. Serum ferritin peaks approximately 7 to 9 days after an intravenous dose of INFeD and returns to baseline after about 3 weeks. Absorption Following intramuscular administration, INFeD is absorbed from the injection site into the capillaries and the lymphatic system. Distribution The circulating iron is bound to the available protein moieties to form hemosiderin or ferritin, or to a lesser extent to transferrin. Elimination The half-life of free iron in the plasma circulation is approximately 5 hours. The half-life of total iron, including both circulating and bound, is approximately 20 hours. These half-life values do not represent clearance of iron from the body. Metabolism Following administration of INFeD, circulating iron dextran is split by the cells of the reticuloendothelial system into its components of iron and dextran. Excretion Negligible amounts of iron are lost via the urinary or alimentary pathways after administration of iron dextran. Dextran, a polyglucose, is either metabolized or excreted. Specific Populations Patients with Renal Impairment In vitro studies have shown that removal of iron dextran by dialysis is negligible. Six different dialyzer membranes were investigated (polysulfone, cuprophane, cellulose acetate, cellulose triacetate, polymethylmethacrylate and polyacrylonitrile), including those considered high efficiency and high flux.