Iron Sucrose

FDA Drug Information • Also known as: Iron Sucrose, Venofer

Brand Names: Iron Sucrose, Venofer
Drug Class: Parenteral Iron Replacement [EPC]
Route: INTRAVENOUS
Dosage Form: INJECTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Iron sucrose injection, USP, an iron replacement product, is a brown, sterile, aqueous, complex of polynuclear iron (III)-hydroxide in sucrose for intravenous use. Iron sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula: [Na 2 Fe 5 O 8 (OH) ·3(H 2 O)] n ·m(C 12 H 22 O 11 ) where: n is the degree of iron polymerization and m is the number of sucrose molecules associated with the iron (III)-hydroxide. Each mL contains 20 mg elemental iron as iron sucrose in water for injection. Iron sucrose injection is available in 10 mL single-dose vials (200 mg elemental iron per 10 mL), 5 mL single-dose vials (100 mg elemental iron per 5 mL), and 2.5 mL single-dose vials (50 mg elemental iron per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and sodium chloride for tonicity. Sodium hydroxide may be added to adjust pH to 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.

What Is Iron Sucrose Used For?

1 INDICATIONS AND USAGE Iron sucrose injection is indicated for the treatment of iron deficiency anemia (IDA) in patients with chronic kidney disease (CKD). Iron sucrose injection is an iron replacement product indicated for the treatment of iron deficiency anemia (IDA) in patients with chronic kidney disease (CKD). ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Population Dose Adult patients Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) ( 2.2 ) 100 mg slow intravenous injection or infusion Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) ( 2.3 ) 200 mg slow intravenous injection or infusion Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) ( 2.4 ) 300 mg or 400 mg intravenous infusion Pediatric patients HDD-CKD ( 2.5 ), PDD-CKD or NDD-CKD ( 2.6 ) 0.5 mg/kg slow intravenous injection or infusion 2.1 Mode of Administration Administer iron sucrose injection only intravenously by slow injection or by infusion. The dosage of iron sucrose injection is expressed in mg of elemental iron. Each mL contains 20 mg of elemental iron. 2.2 Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) Administer iron sucrose injection 100 mg undiluted as a slow intravenous injection over 2 to 5 minutes, or as an infusion of 100 mg diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes, per consecutive hemodialysis session [see How Supplied/Storage and Handling ( 16.2 )] . Administer iron sucrose injection early during the dialysis session (generally within the first hour). The usual total treatment course of iron sucrose injection is 1000 mg. Iron sucrose injection treatment may be repeated if iron deficiency reoccurs. 2.3 Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) Administer iron sucrose injection 200 mg undiluted as a slow intravenous injection over 2 to 5 minutes or as an infusion of 200 mg in a maximum of 100 mL of 0.9% NaCl over a period of 15 minutes. Administer on 5 different occasions over a 14 day period. There is limited experience with administration of an infusion of 500 mg of iron sucrose injection, diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5 to 4 hours on Day 1 and Day 14 [see How Supplied/Storage and Handling ( 16.2 )]. Iron sucrose injection treatment may be repeated if iron deficiency reoccurs. 2.4 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) Administer iron sucrose injection in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions each of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. Dilute iron sucrose injection in a maximum of 250 mL of 0.9% NaCl [see How Supplied/Storage and Handling ( 16.2 )] . Iron sucrose injection treatment may be repeated if iron deficiency reoccurs. 2.5 Pediatric Patients (2 Years of Age and Older) with HDD-CKD for Iron Maintenance Treatment For iron maintenance treatment: Administer iron sucrose injection at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every two weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 0.9% NaCl at a concentration of 1 to 2 mg/mL and administered over 5 to 60 minutes. Do not dilute to concentrations below 1 mg/mL [see How...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:

Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )]

Hypotension [see Warnings and Precautions ( 5.2 )]

Iron Overload [see Warnings and Precautions ( 5.3 )]

Adult patients: The most common adverse reactions (≥2%) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain and peripheral edema. ( 6.1 )

Pediatric patients: The most common adverse reactions (≥2%) are headache, respiratory tract viral infection, peritonitis, vomiting, pyrexia, dizziness, cough, nausea, arteriovenous fistula thrombosis, hypotension and hypertension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Adverse Reactions in Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice. Adverse Reactions in Adult Patients with CKD The frequency of adverse reactions associated with the use of iron sucrose has been documented in six clinical trials involving 231 patients with HDD-CKD, 139 patients with NDD-CKD and 75 patients with PDD-CKD. Adverse reactions reported by ≥2% of treated patients in the six clinical trials for which the rate for iron sucrose exceeds the rate for comparator are listed by indication in Table 1 . Patients with HDD-CKD received 100 mg doses at 10 consecutive dialysis sessions until a cumulative dose of 1000 mg was administered. Patients with NDD-CKD received either 5 doses of 200 mg over 2 weeks or 2 doses of 500 mg separated by fourteen days, and patients with PDD-CKD received 2 doses of 300 mg followed by a dose of 400 mg over a period of 4 weeks. Table 1. Adverse Reactions Reported in ≥2% of Study Populations and for which the Rate for Iron Sucrose Exceeds the Rate for Comparator Body System/Adverse Reactions HDD-CKD NDD-CKD PDD-CKD Iron Sucrose Iron Sucrose Oral Iron Iron Sucrose EPO* Only (N=231) (N=139) (N=139) (N=75) (N=46) % % % % % Subjects with any adverse reaction 78.8 76.3 73.4 72.0 65.2 Ear and Labyrinth Disorders Ear Pain 0 2.2 0.7 0 0 Eye Disorders Conjunctivitis 0.4 0 0 2.7 0 Gastrointestinal Disorders Abdominal pain 3.5 1.4 2.9 4.0 6.5 Diarrhea 5.2 7.2 10.1 8.0 4.3 Dysgeusia 0.9 7.9 0 0 0 Nausea 14.7 8.6 12.2 5.3 4.3 Vomiting 9.1 5.0 8.6 8.0 2.2 General Disorders and Administration Site Conditions Asthenia 2.2 0.7 2.2 2.7 0 Chest pain 6.1 1.4 0 2.7 0 Feeling abnormal 3.0 0 0 0 0 Infusion site pain or burning 0 5.8 0 0 0 Injection site extravasation 0 2.2 0 0 0 Peripheral edema 2.6 7.2 5.0 5.3 10.9 Pyrexia 3.0 0.7 0.7 1.3 0 Infections and Infestations Nasopharyngitis, Sinusitis, Upper respiratory tract infections, Pharyngitis 2.6 2.2 4.3 16.0 4.3 Injury, Poisoning and Procedural Complications Graft complication 9.5 1.4 0 0 0 Metabolism and Nutrition Disorders Fluid overload 3.0 1.4 0.7 1.3 0 Gout 0 2.9 1.4 0 0 Hyperglycemia 0 2.9 0 0 2.2 Hypoglycemia 0.4 0.7 0.7 4.0 0 Musculoskeletal and Connective Tissue Disorders Arthralgia 3.5 1.4 2.2 4.0 4.3 Back pain 2.2 2.2 3.6 1.3 4.3 Muscle cramp 29.4 0.7 0.7 2.7 0 Myalgia 0 3.6 0 1.3 0 Pain in extremity 5.6 4.3 0 2.7 6.5 Nervous System Disorders Dizziness 6.5 6.5 1.4 1.3 4.3 Headache 12.6 2.9 0.7 4.0 0 Respiratory, Thoracic and Mediastinal Disorders Cough 3.0 2.2 0.7 1.3 0 Dyspnea 3.5 5.8 1.4 1.3 2.2 Nasal congestion 0 1.4 2.2 1.3 0 Skin and Subcutaneous Tissue Disorders Pruritus 3.9 2.2 4.3 2.7 0 Vascular Disorders Hypertension 6.5 6.5 4.3 8.0 6.5 Hypotension 39.4 2.2 0.7 2.7 2.2 *EPO=Erythropoietin One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S. trials in HDD-CKD patients (studies A, B and the two post marketing studies) had prior other intravenous iron therapy and were reported to...

Drug Interactions

7 DRUG INTERACTIONS Iron sucrose may reduce the absorption of concomitantly administered oral iron preparations.

Contraindications

4 CONTRAINDICATIONS

Known hypersensitivity to iron sucrose.

Known hypersensitivity to iron sucrose. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Published studies on intravenous iron sucrose treatment after the first trimester of pregnancy have not shown adverse maternal or fetal outcomes (see Data) . Available reports of intravenous iron sucrose use in pregnant women during the first trimester are insufficient to assess the risk of major birth defects and miscarriage. There are risks to the mother and fetus associated with untreated IDA in pregnancy as well as risks to the fetus associated with maternal severe hypersensitivity reactions ( see Clinical Considerations ). Animal reproduction studies of iron sucrose administered to rats and rabbits during the period of organogenesis at elemental iron doses equivalent to the maximum recommended human dose based on body surface area revealed no evidence of harm to the fetus (see Data). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically-recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Iron deficiency anemia during pregnancy should be treated. Untreated IDA in pregnancy is associated with adverse maternal outcomes such as post-partum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight. Fetal/Neonatal Adverse Reactions Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as iron sucrose) which may cause fetal bradycardia, especially during the second and third trimester. Data Human Data Published data from randomized controlled studies and prospective observational...

Overdosage

10 OVERDOSAGE No data are available regarding overdosage of iron sucrose in humans. Excessive dosages of iron sucrose may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. Do not administer iron sucrose to patients with iron overload [see Warnings and Precautions ( 5.3 )]. Iron sucrose is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. Toxicities in single-dose studies in mice and rats, at intravenous iron sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Iron sucrose injection, USP is a brown, sterile, aqueous injection supplied in sterile 2.5 mL, 5 mL, and 10 mL single-dose vials. Each 2.5 mL vial contains 50 mg elemental iron, each 5 mL vial contains 100 mg elemental iron and each 10 mL vial contains 200 mg elemental iron (20 mg/mL). Discard unused portion. NDC 0781-3485-95 50 mg/2.5 mL Single-Dose Vial Packages of 10 NDC 0781-3485-96 50 mg/2.5 mL Single-Dose Vial Packages of 25 NDC 0781-3486-95 100 mg/5 mL Single-Dose Vial Packages of 10 NDC 0781-3486-96 100 mg/5 mL Single-Dose Vial Packages of 25 NDC 0781-3487-94 200 mg/10 mL Single-Dose Vial Packages of 1 NDC 0781-3487-14 200 mg/10 mL Single-Dose Vial Packages of 5 NDC 0781-3487-92 200 mg/10 mL Single-Dose Vial Packages of 10 16.2 Stability and Storage Contains no preservatives. Store in original carton at 20°C to 25°C (68° F to 77° F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Do not freeze. Syringe Stability : Iron sucrose injection, when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental iron per mL, or undiluted (20 mg elemental iron per mL) and stored in a plastic syringe, was found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C) and under refrigeration (4°C ± 2°C). Intravenous Admixture Stability: Iron sucrose injection, when added to intravenous infusion bags (PVC or non-PVC) containing 0.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental iron per mL, has been found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C). Do not dilute to concentrations below 1 mg/mL. Do not mix iron sucrose injection 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 infusion.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.