CPINK S-100 Injection (Iron Sucrose USP)

Table of Content

For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only

Qualitative and Quantitative Composition

Each ml contains:

Ferric Hydroxide in Complex with Sucrose Equivalent to elemental Iron … 20 mg

Water for Injection IP … q.s.

Dosage Form and Strength

Liquid injection for intravenous (IV) use.

Clinical Particulars

Therapeutic Indications

CPINK S-100 Injection is indicated in iron deficiency anemia in which rapid and reliable substitution of iron is required.

Posology and Method of Administration

The dosage of CPINK S-100 Injection is expressed in terms of mg of elemental iron.

Each ml contains 20 mg of elemental iron.

Most CKD patients will require a minimum cumulative repletion dose of 1,000 mg of elemental iron, administered over sequential sessions, to achieve a favorable hemoglobin response and to replenish iron stores. Hemodialysis patients may continue to require therapy with CPINK S-100 Injection or other IV iron preparations at the lowest dose necessary to maintain target levels of hemoglobin, and laboratory parameters of iron storage within acceptable limits.

Administration

CPINK S-100 Injection must only be administered intravenously either by slow injection or by infusion.

Reconstitution

Intravenous Drip Infusion

CPINK S-100 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:

CPINK S-100 dose

(mg of iron)

CPINK S-100 dose

(ml of CPINK S-100)

Maximum dilution volume of sterile 0.9% m/V NaCl solution

Minimum Infusion Time

50 mg

2.5 ml

50 ml

8 minutes

100 mg

5 ml

100 ml

15 minutes

200 mg

10 ml

200 ml

30 minutes

For stability reasons, dilutions to lower CPINK S-100 concentrations are not permissible.

Intravenous Injection

CPINK S-100 Injection may be administered by slow intravenous injection at a rate of 1 ml undiluted solution per minute and not exceeding 10 ml CPINK S-100 (200 mg iron) per injection.

Injection into Venous Line of Dialysis Machine

CPINK S-100 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.

Recommended Adult Dosage

Hemodialysis Dependent-Chronic Kidney Disease Patients (HDD-CKD)

CPINK S-100 Injection may be administered undiluted as a 100 mg slow IV injection over 2 to 5 minutes or as infusion of 100 mg, diluted in a maximum 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)

CPINK S-100 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.

Peritoneal Dialysis Dependent-Chronic Kidney Disease Patients (PDD-CKD)

CPINK S-100 Injection is administered as a total cumulative dose of 1,000 mg in 3 divided doses, given by slow IV infusion, within a 28-day period: 2 infusions of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. The CPINK S-100 Injection dose should be diluted in a maximum of 250 ml of 0.9% NaCl.

Pregnancy & Postpartum Anaemia

  • For Hb 8-9 gm/dl: 100-200 mg to be administered 1 to 2 times per week during pregnancy & postpartum.
  • For Hb < 8 gm/dl: 200 mg twice weekly in pregnancy and 4 times a week in postpartum.

Contraindications

The use of IV iron sucrose injection 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 anaemia not caused by iron deficiency.

Special Warnings and Precautions for Use

Hypersensitivity reactions have been reported with injectable iron products.

Not to be administered by intramuscular route.

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 IV iron sucrose injection 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 reported in patients receiving iron sucrose injection.

Hypotension

Hypotension has been reported frequently in hemodialysis dependent chronic kidney disease patients receiving IV iron. Hypotension also has been reported in non-dialysis dependent and peritoneal dialysis dependent-chronic kidney disease patients receiving IV iron. Hypotension may be related to rate of administration and total dose administered. Caution should be taken to administer IV iron sucrose injection according to recommended guidelines.

Drug Interactions

Drug-drug interactions involving iron sucrose have not been studied. However, like other parenteral iron preparations, iron sucrose may be expected to reduce the absorption of concomitantly administered oral iron preparations.

Use in Special Populations

Pregnant Women

Pregnancy Category B: There are no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Lactating Women

Iron sucrose is shown to be excreted in milk of rats. 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 IV iron sucrose injection is administered to a lactating woman.

Pediatric Patients

Safety and effectiveness of IV iron sucrose injection in pediatric patients have not been established.

Geriatric Patients

No identified differences in responses between the elderly and younger patients have been reported, but greater sensitivity of some older individuals cannot be ruled out.

Effects on Ability to Drive and Use Machines

In the case of symptoms of dizziness, confusion or light headedness following the administration of IV iron sucrose injection, patients should not drive or use machinery until the symptoms have ceased.

Undesirable Effects

Side effects include hypotension, chest pain, diarrhoea, nausea, vomiting, abdominal pain, hypertension, application site reaction, dizziness, dyspnoea, pneumonia, cough, headache, congestive heart failure, cramps, musculoskeletal pain, elevated liver enzymes, skin irritation, pruritus, asthenia, malaise, fever.

Reporting of Side Effects

If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024. By reporting side-effects, you can help provide more information on the safety of this product.

Overdose

Dosages of IV 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. IV iron sucrose injection should not be administered to patients with iron overload and should be discontinued when serum ferritin levels equals or exceeds established guidelines. Particular caution should be exercised to avoid iron overload where anaemia unresponsive to treatment has been incorrectly diagnosed as iron deficiency anaemia.

Symptoms associated with overdosage or infusing IV iron sucrose injection too rapidly includes hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, oedema, and cardiovascular collapse. Most symptoms can be successfully treated with IV fluids, hydrocortisone, and/or antihistamines. Infusing the solution as recommended or at lower rate may also alleviate symptoms.

Pharmacological Properties

Therapeutic Category

Haematinic

Mechanism of action

Iron Sucrose injection is an aqueous complex of poly-nuclear iron (III)-hydroxide in sucrose. Following intravenous administration, it 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.

Pharmacodynamic Properties

Following IV administration, iron sucrose is dissociated by the reticuloendothelial system into iron and sucrose.

Pharmacokinetic Properties

Absorption

In healthy adults treated with IV doses of iron sucrose, its iron component exhibits first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, non-steady state apparent volume of distribution of 10.0 L and steady state apparent volume of distribution 7.9 L. Since iron disappearance from serum depends on the need for iron in the iron stores and iron utilizing tissues of the body, serum clearance of iron is expected to be more rapid in iron deficient patients treated with iron sucrose injection as compared to healthy individuals. The effects of age and gender on the pharmacokinetics of iron sucrose injection have not been studied.

Distribution

In healthy adults receiving IV doses of 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.

Metabolism and Elimination

Following IV administration, iron sucrose is dissociated into iron and sucrose by the reticuloendothelial system. The sucrose component is eliminated mainly by urinary excretion.

Non-Clinical Properties

Animal Toxicology or Pharmacology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been performed with iron sucrose. Iron sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Iron sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay. Iron sucrose at intravenous doses up to 15 mg/kg/day of elemental iron (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.

Description

CPINK S-100 Injection (Iron sucrose injection, USP) 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 34,000-60,000 daltons and a proposed structural formula:

n . m(C12H22O11)]

Where n is the degree of iron polymerization and m is the number of sucrose molecule associated with the iron (III)-hydroxide.

CPINK S-100 Injection is available in 5 ml single dose ampoule (100 mg elemental iron per 5 ml). The drug product contains approximately 30% sucrose W/V (300 mg/ml) and has a pH of 10.5-11.1. The product contains no preservatives. The osmolarity of the injection is between 1150 to 1350 mOsmol/L.

Pharmaceutical Particulars

Incompatibilities

CPINK S-100 Injection must only be mixed with sterile 0.9% m/V sodium chloride solution. No other solutions and therapeutic agents should be used as there is the potential for precipitation and/or interaction. The compatibility with containers other than glass, polyethylene and PVC is not known.

Shelf-life

See on pack

Packaging Information

CPINK S-100 Injection is supplied in 5 ml single dose ampoule.

Each 5 ml ampoule contains 100 mg elemental iron (20 mg/ml). It contains no preservatives.

Storage and Handling Instructions

Store at controlled room temperature (20°C to 25°C). Protect from light. Do not freeze.

Patient Counselling Information

  1. Prior history of reactions to parenteral iron products

Patients should inform on any hypersensitivity reactions faced by them during any prior similar therapy to the treating doctor.

  1. Serious Hypersensitivity Reactions

Advise patients to report any symptoms of hypersensitivity that may develop during and following Iron sucrose administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems

  1. Possible side effects

Side effects include hypotension, chest pain, diarrhoea, nausea, vomiting, abdominal pain, hypertension, application site reaction, dizziness, dyspnoea, pneumonia, cough, headache, congestive heart failure, cramps, musculoskeletal pain, elevated liver enzymes, skin irritation, pruritus, asthenia, malaise, fever.

If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024. By reporting side-effects, you can help provide more information on the safety of this product.

  1. How to store CPINK S-100 Injection?

Store at controlled room temperature (20°C to 25°C). Protect from light. Do not freeze.

5. Contents of the pack and other information

CPINK S-100 is available as pack of 5 ml Ampoule.

Details of Manufacturer

Manufactured in India by: BDR Pharmaceuticals International Pvt. Ltd.

Vanseti Village, PO. Tajpura, Taluka Halol, Dist. Panchmahal-389 350.

Marketed by

CIPLA LTD.

Registered Office:

Cipla House, Peninsula Business Park, Ganpatrao Kadam Marg,

Lower Parel, Mumbai - 400 013, INDIA

Details of Permission or License Number with Date

G/28/1828 dated 14.02.2022

Date of Revision

June 2022