This is indicated for the treatment of iron deficiency in the following indications:

• Where there is a clinical need for a rapid iron supply
• In patients who cannot tolerate oral iron therapy or who are non-compliant
• In active inflammatory bowel disease where oral iron preparations are ineffective
• Non-dialysis dependent chronic kidney disease (NDD-CKD) patients receiving an erythropoietin
• Non-dialysis dependent chronic kidney disease (NDD-CKD) patients not receiving an erythropoietin
• Hemodialysis dependent chronic kidney disease (HDD-CKD) patients receiving an erythropoietin
• Peritoneal dialysis dependent chronic kidney disease (PDD-CKD) patients receiving an erythropoietin
• It is also indicated in the treatment of iron deficiency anemia in patients undergoing surgical procedures, patients donating blood, and postpartum patients.

The therapeutic class of Iron Sucrose is haematinic. Iron Sucrose Injection USP is a brown, sterile, aqueous complex of polynuclear iron (III) hydroxide in sucrose for intravenous use. The drug product contains approximately 30% sucrose w/v (300 mg/ml) and has a pH of 10.5-11.1. Following intravenous administration, Iron Sucrose Injection is dissociated into iron and sucrose by the reticuloendothelial system, and iron is transferred from the blood to a pool of iron in the liver and bone marrow. Ferritin, an iron storage protein, binds and sequesters iron in a nontoxic form, from which iron is easily available. Iron binds to plasma transferrin, which carries iron within the plasma and the extracellular fluid to supply the tissues. The transferrin receptor, located in the cell, and the transferrin-receptor complex is returned to the cell membrane. Transferrin without iron (apotransferrin) is then released to the plasma. The intracellular iron becomes (mostly) hemoglobin in circulating red blood cells (RBCs). Transferrin synthesis is increased and ferritin production reduced in iron deficiency. The converse is true when iron is plentiful. Its elimination half-life is 6 hours, total clearance is 1.2 L/h, non-steady state apparent volume of distribution is 10.0 L, and steady state apparent volume of distribution is 7.9 L. In Iron Sucrose, its iron component appears to distribute mainly in blood and to some extent in extravascular fluid. A significant amount of the administered iron distributes in the liver, spleen and bone marrow, and the bone marrow is an iron trapping compartment and not a reversible volume distribution. The sucrose component is eliminated mainly through urinary excretion.

Adults and Elderly: 5-10 ml Iron Sucrose Injection (100-200 mg Iron) once to three times a week depending on the hemoglobin level.

Children: There is limited data on children under study conditions. If there is a clinical need, it is recommended not to exceed 0.15 ml Iron Sucrose Injection (3 mg Iron) per kg body weight once to three times per week depending on the haemoglobin level.

Administration

Intravenous injection: Iron Sucrose Injection can also be administered undiluted by slow intravenous injection at the (normal) recommended rate of 1 ml Iron Sucrose Injection (20 mg Iron) per minute [5 ml Iron Sucrose Injection (100 mg Iron) in 2 to 5 minutes]. A maximum of 10 ml Iron Sucrose Injection (200 mg Iron) can be injected per injection. Before administration of the therapeutic dose in a new patient, a test dose of 1 ml Iron Sucrose Injection (20 mg Iron) in adults and in children with a body weight greater than 14 kg and half the daily dose (1.5 mg Iron/kg) in children with a body weight less than 14 kg should be injected over 1 to 2 minutes. If no adverse reactions occur within a waiting period of 15 minutes, the remaining portion of the injection can be administered at recommended speed. After an injection the arm of the patient should be extended.

Infusion: Iron Sucrose Injection should preferably be administered by drip infusion (in order to reduce the risk of hypotensive episodes and paravenous injection) in a dilution of 1 ml Iron Sucrose Injection (20 mg Iron) in max. 20 ml 0.9% w/v Sodium Chloride [5 ml (100 mg Iron) in max. 100 ml 0.9% w/v NaCI etc. up to 25 ml (500 mg Iron) in max. 500 ml 0.9% w/v NaCI]. Dilution must take place immediately prior to infusion and the solution should be administered as follows: 100 mg Iron in at least 15 minutes; 200 mg Iron in at least 30 minutes; 400 mg Iron In at least 1.5 hours, and 500 mg Iron in at least 3.5 hours. Further of the maximum tolerated single dose of 7 mg Iron/kg body weight, an Infusion time of at least 3.5 hours has to be respected, independently of the total dose.

Before administration of the therapeutic dose in a new patient the first 20 mg Iron in adults and in children with a body weight greater than 14 kg and half the daily dose (1.5 mg lron/kg) in children with a body weight less than 14 kg should be infused over 15 minutes as a test dose. If no adverse reactions occur, the remaining portion of the infusion can be administered at recommended speed.

Drug-drug interactions involving Iron Sucrose have not been studied. Iron Sucrose Injection should not be administered concomitantly with oral iron preparations since the absorption of oral iron is reduced. Oral iron therapy should not be given until 5 days after the last injection.

The use of Iron Sucrose is contraindicated in patients with evidence of iron overload, in patients with known hypersensitivity to Iron Sucrose or any of its inactive components, and in patients with anemia not caused by iron deficiency. It is also contraindicated in patients with a history of allergic disorders including asthma, eczema and anaphylaxis, liver disease and infections.

• Adverse reactions, whether or not related to Iron Sucrose injection, are as follows: hypotension, cramps/leg cramps, nausea, headache, vomiting, and diarrhea. Some of these symptoms may be seen in patients with chronic renal failure or on hemodialysis not receiving intravenous iron.
• Body as a Whole: headache, fever, pain, asthenia, unwell, malaise, accidental injury
• Cardiovascular Disorders General: hypotension, chest pain, hypertension, hypervolemia
• Gastrointestinal Disorders: nausea, vomiting, abdominal pain, elevated liver enzymes
• Central and Peripheral Nervous System: dizziness
• Musculoskeletal System: cramps/leg cramps, musculoskeletal pain
• Respiratory System: dyspnea, pneumonia, cough
• Skin and Appendages: pruritus, application site reaction
• Hypersensitivity reactions: In safety studies, several patients experienced mild or moderate hypersensitivity reactions presenting with wheezing, dyspnea, hypotension, rashes, or pruritus. Anaphylactoid reactions including patients who experienced serious or life-threatening reactions (anaphylactic shock, loss of consciousness or collapse, bronchospasm with dyspnea, or convulsion) associated with Iron Sucrose administration can occur. Therefore, patients should be given a small test dose initially.

Pregnancy Category B. No adequate and well-controlled studies exist in pregnant women. This drug should be used during pregnancy only if clearly needed. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Iron Sucrose is administered to a nursing woman.

General: Because body iron excretion is limited and excess tissue iron can be hazardous, caution should be exercised to withhold iron administration in the presence of evidence of tissue iron overload. Patients receiving Iron Sucrose require periodic monitoring of hematologic and haematinic parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Iron therapy should be withheld in patients with evidence of iron overload. Transferrin saturation values increase rapidly after IV administration of Iron Sucrose; thus, serum iron values may be reliably obtained 48 hours after IV dosing.

Hypersensitivity Reactions: Serious hypersensitivity reactions have been rarely reported in patients receiving Iron Sucrose. Several cases of mild or moderate hypersensitivity reactions were observed in these studies.

Hypotension: Hypotension has been reported frequently in hemodialysis patients receiving intravenous iron. Hypotension following administration of Iron Sucrose may be related to the rate of administration and the total dose administered. Caution should be taken to administer Iron Sucrose according to recommended guidelines.

Pediatric Use: Safety and effectiveness of Iron Sucrose in pediatric patients have not been established.

Geriatric Use: No overall differences in safety were observed between elderly subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Injection into dialyser: Iron Sucrose Injection may be administered directly into the venous limb of the dialyser under the same conditions as for intravenous injection.

Hemodialysis Dependent-Chronic Kidney Disease Patients (HDD-CKD): Iron Sucrose Injection may be administered undiluted as a 100 mg 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 for a total cumulative dose of 1,000 mg.

Non-Dialysis Dependent-Chronic Kidney Disease Patients (NDD-CKD): Iron Sucrose Injection is administered as a total cumulative dose of 1,000 mg over a 14-day period as a 200 mg slow IV injection undiluted over 2 to 5 minutes on 5 different occasions within the 14-day period.

Dosages of Iron Sucrose Injection in excess of iron needs may lead to accumulation of iron in storage sites, leading to hemosiderosis. Periodic monitoring of iron parameters such as serum ferritin and transferrin saturation may assist in recognizing iron accumulation. Iron Sucrose should not be administered to patients with iron overload and should be discontinued when serum ferritin levels equal or exceed established guidelines. Particular caution should be exercised to avoid iron overload where anemia unresponsive to treatment has been incorrectly diagnosed as iron deficiency anemia. Symptoms associated with overdosage or infusing Iron Sucrose too rapidly include hypotension, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse. Most symptoms have been successfully treated with IV fluids, hydrocortisone, and/or antihistamines. Infusing the solution as recommended or at a slower rate may also alleviate symptoms.

Parenteral Iron Preparations

Store in a cool (15°C-30°C) and dry place, protected from light. Keep out of the reach of children. Do not freeze.