In-House. Solution for Injection A dark brown coloured, slightly viscous solution filled in ampoule.

Transcription

1 Iron Sucrose Injection USP 20 mg/ml Iron sucrose Eq. to Elemental Iron 01 Iron sucrose Eq. to Elemental Iron In-House 02 Sodium Hydroxide BP Eq. to Q.S. to adjust ph Iron supplement ph Adjustment 03 Water for Injections BP Q.S. Vehicle Solution for Injection A dark brown coloured, slightly viscous solution filled in ampoule. I. For the treatment of iron deficiency anemia in patients with chronic kidney disease (CKD). II. For the treatment of iron deficiency in the following indications: Where there is a clinical need to deliver iron rapidly to iron stores, In patients who cannot tolerate oral iron therapy or who are noncompliant,

2 In active inflammatory bowel disease where oral iron preparations are ineffective. The diagnosis of iron deficiency must be based on appropriate laboratory tests. Iron Sucrose must only be administered IV either by slow injection or by infusion, not by intramuscular injection. Iron Sucrose treatment may be repeated if iron deficiency reoccurs. The cumulative dose of Iron Sucrose Injection must be calculated for each patient individually and must not be exceeded. Calculation of dosage The total cumulative dose of Iron Sucrose Injection, equivalent to the total iron deficit (mg), is determined by the haemoglobin level (Hb) and body weight (BW). The dose of Iron Sucrose Injection must be individually calculated for each patient according to the total iron deficit calculated with the following Ganzoni formula, for example: Below 35 kg BW: Target Hb = 13 g/dl and storage iron = 15 mg/kg BW 35 kg BW and above: Target Hb = 15 g/dl and storage iron = 500 mg * Factor 2.4 = (iron content of Hb = 0.34%) x 0.07 (blood volume = 7% of BW) x 1000 (conversion of [g] to [mg]) x 10

3 Total amount of Iron Sucrose Injection (ml) to be administered according to body weight, actual Hb level and target Hb level*: 30 kg 47.5 ml 42.5 ml 37.5 ml 32.5 ml 35 kg 62.5 ml 57.5 ml 50 ml 45 ml 40 kg 67.5 ml 60 ml 55 ml 47.5 ml 45 kg 75 ml 65 ml 57.5 ml 50 ml 50 kg 80 ml 70 ml 60 ml 52.5 ml 55 kg 85 ml 75 ml 65 ml 55 ml 60 kg 90 ml 80 ml 67.5 ml 57.5 ml 65 kg 95 ml 82.5 ml 72.5 ml 60 ml 70 kg 100 ml 87.5 ml 75 ml 62.5 ml 75 kg 105 ml 92.5 ml 80 ml 65 ml 80 kg ml 97.5 ml 82.5 ml 67.5 ml 85 kg ml ml 85 ml 70 ml 90 kg ml ml 90 ml 72.5 ml * Below 35 kg BW: Target Hb = 13 g/dl 35 kg BW and above: Target Hb = 15 g/dl 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. Posology Adults 5-10 ml of Iron Sucrose Injection ( mg iron) 1 to 3 times a week. For administration time and dilution ratio see Method of administration. Paediatric population The use of Iron Sucrose Injection has not been adequately studied in children and, therefore, Iron Sucrose Injection is not recommended for use in children.

4 Iron Sucrose Injection 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 Injection 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: Iron Sucrose Injection dose Iron Sucrose Injection dose Maximum dilution volume of sterile Minimum Infusion Time (mg of iron) (ml of Iron Sucrose Injection) 0.9% m/v NaCl solution 50 mg 2.5 ml 50 ml 8 minutes 100 mg 5.0 ml 100 ml 15 minutes 200 mg 10.0 ml 200 ml 30 minutes For stability reasons, dilutions to lower Iron Sucrose Injection concentrations are not permissible. Intravenous injection Iron Sucrose Injection may be administered by slow intravenous injection at a rate of 1 ml undiluted solution per minute and not exceeding 10 ml Iron Sucrose Injection (200 mg iron) per injection. Injection into venous line of dialysis machine Iron Sucrose Injection may be administered during a haemodialysis session directly into the venous line of the dialysis machine under the same conditions as for intravenous injection.

5 Anemia not attributable to iron deficiency, iron overload or disturbances in utilisation of iron. Known hypersensitivity to Iron Sucrose, parenteral iron compounds. 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. However, in several studies performed in patients who had a history of a hypersensitivity reaction to iron dextran or ferric gluconate, Iron Sucrose Injection was shown to be well tolerated. 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 reactions to parenteral iron complexes in patients with immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis). Iron Sucrose 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 Sucrose Injection injection. If hypersensitivity reactions or signs of intolerance occur during administration, the treatment must be stopped immediately. Facilities for cardio respiratory resuscitation and equipment for handling acute anaphylactic/anaphylactoid reactions should be available, including an injectable

6 Module-1 Administrative Information and Product Information 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 Sucrose 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 Sucrose Injection at the injection site can lead to pain, inflammation and brown discoloration of the skin Interaction with other medicinal products and other forms of interaction As with all parenteral iron preparation, Iron Sucrose Injection should not be administered concomitantly with oral iron preparations since the absorption of oral iron is reduced. Therefore, oral Iron therapy should be started at least 5 days after the last injection of Iron Sucrose Injection Fertility, Pregnancy and Lactation Pregnancy: Pregnancy Category B. A careful risk/benefit evaluation is therefore required before use during pregnancy and should not be used during pregnancy unless clearly necessary. Nursing Mothers: Caution should be exercised during Iron sucrose administration. Iron Sucrose Injection USP 20 mg/ml

7 In the case of symptoms of dizziness, confusion or light headedness following the administration of Iron Sucrose Injection, patients should not drive or use machinery until the symptoms have ceased. In general anaphylactoid reactions are potentially the most serious adverse reactions: Following adverse drug reactions have been reported with at least a possible causal relationship [ : Nervous system: Common: transient metallic taste; Uncommon: headache, dizziness; Rare: paraesthesia, syncope, loss of consciousness, burning sensation. Cardio-vascular disorders Uncommon: hypotension, tachycardia, palpitations, hypertension. Respiratory, thoracic and mediastinal disorders Uncommon: bronchospasm, dyspnoea. Gastrointestinal system Uncommon: nausea, vomiting, abdominal pain, diarrhoea. Skin and subcutaneous tissue disorders Uncommon: pruritus, urticaria, rash, exanthema. Musculoskeletal, connective tissue and bone disorders Uncommon: muscle cramps, myalgia. General disorders and administration site disorders Uncommon: fever, shivering, flushing, chest pain and tightness. Injection site disorders such as superficial phlebitis, burning, swelling; Rare: arthralgia, peripheral oedema, fatigue, asthenia, malaise, feeling hot, oedema. Immune system disorders Rare: anaphylactoid reactions. In paediatric patients with CKD: The most common treatment-emergent adverse reactions (> 2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness

8 (4%), cough (4%), renal transplant (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%). 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. Iron sucrose is an aqueous complex of poly-nuclear iron (III)-hydroxide in sucrose. Following intravenous administration, Iron sucrose is dissociated into iron and sucrose and the iron is transported as a complex with transferrin to target cells including erythroid precursor cells. The iron in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with iron sucrose containing 100 mg of 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. In healthy adults administered intravenous doses of iron sucrose, its iron component exhibited first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, and steady state apparent volume of distribution of 7.9 L. The iron component appeared to distribute mainly in blood and to some extent in extravascular fluid. In patients with iron deficiency showed that a significant amount of the administered iron is distributed to liver, spleen and bone marrow and that the bone marrow is an irreversible iron trapping compartment. The

9 sucrose component is eliminated mainly by urinary excretion. Some iron was also eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration. In pediatric patients, mean C max and and 1.67-fold higher than dose adjusted adult C max and AUC values. Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity and toxicity to reproduction and development. Sodium Hydroxide Water for Injections Not applicable. 24 months Store below 30 C. Do not Freeze. Protect from light. A dark brown coloured, slightly viscous solution filled in 5 ml amber glass ampoule. Such 1 labeled ampoule is packed in HIPS tray. Such 1 tray is packed in Printed Carton with Packing Insert. Any unused product or waste material should be disposed of in accordance with local requirements.

10 Lincoln Pharmaceuticals Limited Trimul Estate, Khatraj, Taluka: Kalol, District: Gandhinagar Gujarat, India. Telephone no.: Fax: Website: Lincoln Parenteral Limited 11, Trimul Estate, Khatraj, Taluka: Kalol, District: Gandhinagar Gujarat, India. Telephone no.: Fax: Website: To be included after obtaining first registration. It will be applicable after registration of this product Not Applicable Not Applicable