Irsuc

Iron (as Ferric Hydroxide Sucrose Complex) is a sterile, dark brown slightly viscous solution of ferric hydroxide in complex with Sucrose in Water for Injection filled in a 5 mL amber coloured glass ampoule containing Ferric Hydroxide in complex with Sucrose as its active ingredient. Its chemical name is (2R,3R,4S,5S,6R)-2-[(2S,3S,4S,5R)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6(hydroxymethyl)oxane-3,4,5-tri.iron(3+); Oxygen (2-). It has a molecular weight of 34,000 to 64,000 daltons and its molecular formula is [Na₂Fe₅O₈(OH)·3(H₂O)]n·m(C₁₂H₂₂O₁₁).
Each mL contains: Ferric Hydroxide in Complex with Sucrose equivalent to elemental Iron 20 mg, Water for Injection BP q.s.

Hematinic.
Pharmacology: Pharmacodynamics: Following intravenous administration of Iron (as Ferric Hydroxide Sucrose Complex) is dissociated by the endothelial system into iron and sucrose. In 22 hemodialysis patients on erythropoietin (recombinant human erythropoietin) therapy treated with iron sucrose containing 100 mg iron, three times weekly for three weeks, significant increases in serum iron and serum ferritin and significant decreases in total iron binding capacity occurred four weeks from the initiation of iron sucrose treatment.
Pharmacokinetics: Following intravenous injection of a single dose of iron sucrose injection USP containing 100 mg iron in healthy volunteers, maximum iron levels, averaging 538 Mmol/L, were obtained 10 minutes after injection. The volume of distribution of central compartment corresponded well to the volume of plasma (approximately 3 litres).
The iron injected was rapidly cleared from the plasma, the terminal half-life being approx. 6h. The volume of distribution at steady state was about 8 litres, indicating a low iron distribution in the body fluid. Due to the lower stability of iron sucrose in comparison to transferrin, a competitive exchange of iron to transferrin was observed. This result in iron transport of approx. 31 mg iron/24h.
Renal elimination of iron, occurring in the first 4h after injection, corresponds to less than 5% of the total body clearance. After 24h the plasma levels of iron were reduced to the pre-dose iron level and about 75% of the dosage of sucrose was excreted.
Distribution: Following intravenous administration of iron sucrose, the iron component appears to distribute mainly in blood and to some extent in extravascular fluid. Significant amount of administered iron is distributed in the liver, spleen and bone marrow.
Metabolism and Elimination: Following intravenous administration, iron sucrose dissociated into iron and sucrose by the reticuloendothelial system. The sucrose component is eliminated mainly by urinary excretion.

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; in chronic kidney disease when oral iron preparations are less effective.
Iron sucrose Injection USP is indicated for the treatment of iron deficiency in the following indications: Pre-existing (moderate to severe) anemia; patients not responding or having poor compliance with oral iron supplements; pre and postoperative period; postpartum anemia and postpartum haemorrhage; patients with poor iron absorption (bowel operations or diseases); patients with severe renal impairment.
Treatment of Iron Deficiency Anemia in the following patients: Hemodialysis Dependent Chronic Kidney Disease (HDD-CKD) patients receiving an Erythropoietin; Peritoneal Dialysis Dependent Chronic Kidney Disease (PDD-CKD) patients receiving an Erythropoietin; Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD) patients receiving or not receiving an Erythropoietin; During pregnancy and postpartum.

Monitor carefully patients for signs and symptoms of hypersensitivity reactions during and following each administration of iron sucrose.
Iron sucrose should only be administered when staff trained to evaluate and manage anaphylactic reactions is immediately available, in an environment where full resuscitation facilities can be assured. The patient should be observed for adverse effects for at least 30 minutes following each Iron Sucrose Injection (see Adverse Reactions).
Dosage: The cumulative dose of Iron Sucrose must be calculated for each patient individually and must not be exceeded.
Calculation of dosage: The total cumulative dose of Iron Sucrose, equivalent to the total iron deficit (mg), is determined by the haemoglobin level (Hb) and body weight (BW). The dose of Iron Sucrose must be individually calculated for each patient according to the total iron deficit calculated with the following Ganzoni formula, for example: see Equation.

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Total amount of Iron Sucrose (mL) to be administered according to body weight, actual Hb level and target Hb level*: See Table 1.

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To convert Hb (mM) to Hb (g/dl), multiply the former by 1.6.
If the total necessary dose exceeds the maximum allowed single dose, then the administration must be divided.
Dosage: Adults: 5-10 mL Iron Sucrose (100-200 mg Iron) 1 to 3 times a week. For administration time and dilution ratio see "Method of administration" as follows.
Pediatric Population: The use of Iron Sucrose has not been adequately studied in children and, therefore, Iron Sucrose is not recommended for use in children.
Method of administration: Iron Sucrose must only be administered by the intravenous route. This may be by a slow Intravenous injection, by an intravenous drip infusion or directly into the venous line of the dialysis machine.
Intravenous drip infusion: Iron Sucrose must only be diluted in sterile 0.9% m/V sodium chloride (NaCl) solution. Dilution must take place immediately prior to infusion and the solution should be administered as follows: See Table 2.

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For stability reasons, dilutions to lower Iron Sucrose concentrations are not permissible.
Intravenous Injection: Iron Sucrose may be administered by slow intravenous injection at a rate of 1 mL undiluted solution per minute and not exceeding 10 mL Iron Sucrose (200 mg Iron) per Injection.
Injection into venous line of dialysis machine: Iron Sucrose may be administered during a haemodialysis session directly into the venous line of the dialysis machine under the same conditions as for intravenous injection.

Overdosage can cause acute iron overloading which may manifest itself as haemosiderosis. Overdosage should be treated, if required, with an iron chelating agent.
Dosages of iron sucrose 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.

The use of Iron (as Ferric Hydroxide Sucrose Complex) is contraindicated in the following conditions: Hypersensitivity to the active substance, to Iron Sucrose or any of its excipients.
Known serious hypersensitivity to other parenteral iron products. Anaemia not caused by iron deficiency.
Evidence of iron overload or hereditary disturbances in utilisation of iron.
The use of iron sucrose is contraindicated in patients with evidence of iron overload, in patients with known hypersensitivity to it or any of its inactive components, and in patients with anemia not caused by iron deficiency.

Hypersensitivity reactions have been reported with injectable iron products.

Parenterally administered iron preparations can cause hypersensitivity reactions including serious and potentially fatal anaphylactic/anaphylactoid reactions. Hypersensitivity reactions have also been reported after previously uneventful doses of parenteral iron complexes including iron sucrose. There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arteriospasm that can result in myocardial infarction, see Adverse Reactions). In several studies performed in patients who had a history of a hypersensitivity reaction to iron dextran or ferric gluconate, IRSUC was shown to be well tolerated. For known serious hypersensitivity to other parenteral iron product see Contraindications. The risk of hypersensitivity reactions is enhanced for patients with known allergies including drug allergies, including patients with a history of severe asthma, eczema or other atopic allergy. There is also an increased risk of hypersensitivity conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis). Iron Injection should only be administered when staff trained to evaluate and manage anaphylactic reactions is immediately available, in an environment where full resuscitation facilities can be assured. Each patient should be observed for adverse effects for at least 30 minutes following each Iron injection. If hypersensitivity reactions or signs of intolerance occur during administration, the treatment must be stopped immediately. Facilities for cardiorespiratory resuscitation and equipment for handling acute anaphylactic/anaphylactoid reactions should be available, including an injectable 1:1000 adrenaline solution. Additional treatment with antihistamines and/or corticosteroids should be given as appropriate. In patients with liver dysfunction, parenteral iron should only be administered after careful risk/benefit assessment. Parenteral iron administration should be avoided in patients with hepatic dysfunction where iron overload is a precipitating factor, in particular Porphyria Cutanea Tarda (PCT). Careful monitoring of iron status is recommended to avoid iron overload. Parenteral iron should be used with caution in the case of acute or chronic infection. It is recommended that the administration of Iron Injection is stopped in patients with bacteraemia. In patients with chronic infection, a risk/benefit evaluation should be performed. Paravenous leakage must be avoided because leakage of Iron Injection at the injection site can lead to pain, inflammation and brown discoloration of the skin. Iron Injection contains up to 7 mg sodium per mL, equivalent to 0.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
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 requires periodic monitoring of hematologic and hematinic parameters. 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 hrs after IV dosing.
Hypersensitivity Reactions: Serious hypersensitivity reactions have been rarely reported in patients receiving iron sucrose.
Hypotension: Hypotension has been reported in chronic kidney disease patients receiving intravenous iron. Hypotension following administration of iron sucrose may be related to rate of administration and total dose administered. Caution should be taken to administer iron sucrose according to recommended guidelines.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: No long-term studies in animals have been performed to evaluate the carcinogenic potential of iron sucrose.
Use in Pregnancy and Lactation: See Use in Pregnancy & Lactation section for further information.
Use in Children: Safety and effectiveness of iron sucrose in pediatric patients have not been established.
Use in the Elderly: There are no identified differences in responses between elderly and younger patients, but greater sensitivity of some of the older individuals cannot be ruled out.

Data on limited number of exposed pregnancies indicated no adverse effects of Iron Sucrose Injection USP on pregnancy or on the health of the foetus/newborn child. No well-controlled studies in pregnant women are available to date. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
Nevertheless, risk/benefit evaluation is required.
Iron sucrose Injection USP should only be used in pregnant women in whom oral iron is ineffective or cannot be tolerated and the level of anaemia is judged sufficient to put the mother or foetus at risk.
Non metabolised Iron sucrose Injection USP is unlikely to pass into the mother's milk. No well-controlled clinical studies are available to date. Animal studies do not indicate direct or indirect harmful effects to the nursing child.
Use in Pregnancy: Pregnancy Category B. No adequate and well controlled studies in pregnant women have been reported. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Use in Lactation: It is not known whether this drug is excreted in human milk. Caution should be exercised when iron sucrose is administered to a nursing woman.

The most frequently reported adverse drug reaction (ADRc) of Iron Sucrose in clinical trials were transient taste perversion, hypotension, fever and shivering, injection site reaction and nausea, occurring in 0.5 to 105% of the patients. Non-serious anaphylactoid reactions occurred rarely. In general anaphylactoid reactions are potentially the most serious adverse reaction.
The most commonly reported adverse drug reaction in clinical trials with Iron Sucrose was dysgeusia, which occurred with a rate of 4.5 events per 100 subjects. The most important serious adverse drug reactions associated with Iron Sucrose are hypersensitivity reactions, which occurred with a rate of 0.25 events per 100 subjects in clinical trials. The adverse drug reactions reported after the administration of Iron Sucrose in 4,046 subjects in clinical trials as well as those reported from the post-marketing setting are presented in the table as follows. (See Table 3.)

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Side effects include hypotension, chest pain, hypervolemia, CHF, cramps, musculoskeletal pain, diarrhea, nausea, vomiting, abdominal pain, elevated liver enzymes, skin irritation, pruritis, application site reaction, dizziness, dyspnea, pneumonia, cough, headache, fever, asthenia, malaise.

As with all parenteral iron preparations, Iron Sucrose Injection USP should not be administered concomitantly with oral iron preparations since the absorption of oral iron preparations is reduced. Therefore, oral iron therapy should be started at least 5 days after the last injection of Iron sucrose injection USP.

Special precautions for disposal and other handling: Ampoules or vials should be visually inspected for sediment and damage before use. Use only those containing a sediment free and homogenous solution. Iron Injection must not be mixed with other medicinal products except sterile 0.9% m/V sodium chloride solution for dilution. For instructions on dilution of the product before administration, see Dosage & Administration. The diluted solution must appear as brown and clear.
Each ampoule of IRSUC is intended for single use only.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store at temperature not exceeding 30°C. Protect from light. Do not freeze.

Vitamins & Minerals (Pre & Post Natal) / Antianemics

B03AC - Iron, parenteral preparations ; Used in the treatment of anemia

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