Consumer medicine information

Ferrosig Injection

Iron polymaltose complex

BRAND INFORMATION

Brand name

Ferrosig Injection

Active ingredient

Iron polymaltose complex

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ferrosig Injection.

What is in this leaflet?

This leaflet answers some common questions about FERROSIG INJECTION.

It does not contain all the available information.

It does not take place of talking to your doctor or pharmacist.

All medicines have risks and benefits.

Your doctor has weighed the risks of using FERROSIG INJECTION against the benefits this medicine is expected to have for you.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What is FERROSIG INJECTION?

The name of your medicine is FERROSIG Injection.

FERROSIG injection is an iron supplement.

It contains iron in a form that can be used by your body to build up iron reserves that are needed for your system to operate properly.

What is FERROSIG INJECTION used for?

FERROSIG INJECTION is used in cases of iron deficiency (too little iron in the system).

FERROSIG INJECTION is used when dosage by mouth is impractical, the anaemia is severe or disturbances in the gastro-intestinal tract make absorption difficult or uncertain.

FERROSIG INJECTION is also used for treating iron deficiency states discovered in the third trimester of pregnancy and in circumstances where contact between patient and doctor only occurs at irregular intervals.

Your doctor however, may have prescribed and used FERROSIG INJECTION for another reason.

Ask your doctor if you have any questions about why FERROSIG INJECTION has been prescribed for you. A doctor's prescription is required for FERROSIG INJECTION.

Before you are given FERROSIG INJECTION

When you must not be given it:

Do not use FERROSIG INJECTION if you have ever had an allergic reaction to:

  1. FERROSIG INJECTION or other iron preparations.
  2. any of the other ingredients in FERROSIG.

You must tell your doctor if:

  1. You have had an allergic reaction to iron supplements.
Some of the symptoms of an allergic reaction may include skin rash and itching. Other reactions may include nausea, vomiting and diarrhoea.
There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute coronary arteriospasm that can result in myocardial infarction).
  1. You are allergic to any other medicines or any foods, dyes or preservatives.
  2. You have any other medical conditions or health problems including:
Liver and/or kidney problems, Bronchial asthma, arthritis, heart disease
  • Allergies
  • Infections
  1. you are pregnant or intend to become pregnant.
Foetal bradycardia may occur following administration of parenteral irons. It is usually transient and a consequence of a hypersensitivity reaction in the mother. The unborn baby should be carefully monitored during administration of parenteral irons to pregnant women.
Like most medicines, FERROSIG INJECTION is not recommended in the first trimester of pregnancy. Your doctor will discuss the possible risks and benefits of using FERROSIG INJECTION during pregnancy.

If you have not told your doctor about any of the above, tell them before you are given any FERROSIG INJECTION.

When you must not be given FERROSIG INJECTION

  1. If the ampoule contents are discoloured or show signs of visible sedimentation.
  2. After the expiry date printed on the pack has passed.
The medication may have no effect at all, or worse, it may give an entirely unexpected effect if you use it after the expiry date.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may interact with FERROSIG INJECTION.

These include:

  • Drugs that are used to treat heart disease and high blood pressure known as ACE inhibitors (e.g. captopril, enalapril, fosinopril, lisinopril or quinalapril).
  • Oral iron supplements.

Your doctor or pharmacist has more information on medicines to avoid while taking FERROSIG INJECTION.

How FERROSIG INJECTION is given

FERROSIG INJECTION is given in a prescribed manner into the muscle.

The injection technique is well defined and must be adhered to.

Failure to inject as recommended could result in persistent staining of the skin.

FERROSIG INJECTION should never be injected into the arm or other exposed areas.

Your doctor has detailed information on the correct injection technique.

FERROSIG INJECTION may also be administered intravenously. This should only be done by a doctor in a hospital.

How much to inject

The dose of FERROSIG INJECTION is determined by the amount of iron found in your system using a blood test.

Your doctor has information on the correct dosage requirement for different haemoglobin or iron levels.

Your doctor will decide what dose and how you are administered FERROSIG INJECTION.

How long to use it

Your doctor will tell you how long the course of FERROSIG INJECTION will last.

While you are using FERROSIG INJECTION

Things you must do

Tell your doctor if:

  • Your symptoms do not improve within a few days, or if they become worse.
  • You develop any form of skin rash and/or itching or difficulty in breathing while using FERROSIG INJECTION.
  • You become pregnant while using FERROSIG INJECTION.

If you have to get any blood or urine tests done tell your doctor and nurse that you are using FERROSIG INJECTION.

Tell any doctor, dentist and pharmacist who are treating you that you are on a course of FERROSIG INJECTION.

Tell your doctor if you feel that FERROSIG INJECTION is not helping your condition.

Tell your doctor if, for any reason, FERROSIG INJECTION has not been used exactly as prescribed. Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Things you must not do

Do not take any oral iron supplements while using FERROSIG INJECTION.

Side Effects or Adverse Reactions

Tell your doctor or pharmacist if you do not feel well while you are using FERROSIG INJECTION.

FERROSIG INJECTION helps most people with low haemoglobin (or iron) but it may have some unwanted side effects in a few people.

Side effects that have been reported by people using FERROSIG INJECTION include:

  • Kounis syndrome - frequency not known.
  • In pregnancy, associated foetal bradycardia may occur with parenteral iron preparations.
  • Pain at site of injection
  • Local redness or swelling at the injection site
  • Lower quadrant abdominal pain
  • Headache
  • Nausea, vomiting
  • Joint and muscle pains
  • Faintness, sweating, flushing
  • Difficulty breathing
  • Dizziness on standing from a sitting position.

Some adverse reactions can be delayed and these may include:

  • Sensation of stiffening of the arms, legs or face
  • Chest and back pain
  • Faintness
  • Chills, fever, rash
  • hypophosphataemia including hypophosphataemic osteomalacia

Incorrect injection technique could result in staining of the skin.

FERROSIG INJECTION may cause other side effects. If you have any other side effects, check with your doctor.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using FERROSIG INJECTION

Storage

Keep FERROSIG INJECTION where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Store FERROSIG INJECTION at below 25°C. Do not freeze. Protect from light.

Do not leave FERROSIG INJECTION in the car or on windowsills. Heat can destroy some medicines.

Disposal

If your doctor tells you to stop using FERROSIG INJECTION or it has passed its expiry date, ask your pharmacist what to do with any FERROSIG INJECTION left over.

Further Information

This is not all the information that is available on FERROSIG INJECTION. If you need more information, ask a doctor or pharmacist.

Product Description

What it looks like

FERROSIG INJECTION is a slightly viscous, dark reddish-brown liquid and is supplied in 2mL ampoules for injection. Each ampoule contains 318 mg iron polymaltose equivalent to 100 mg iron III (50 mg per mL).

Active ingredient

Iron polymaltose complex is the active ingredient in FERROSIG INJECTION.

List of inactive ingredients
Water for injections and hydrochloric acid or sodium hydroxide (for pH adjustment of the formulation).

The Australian Product Registration number for FERROSIG INJECTION is AUSTR 82435.

SPONSOR

Sigma Company Ltd
3 Myer Place, Rowville,
Victoria, 3178 Australia

CMI prepared in April 2011.

CMI updated 31 May 2022.

Published by MIMS July 2022

BRAND INFORMATION

Brand name

Ferrosig Injection

Active ingredient

Iron polymaltose complex

Schedule

S4

 

1 Name of Medicine

Iron polymaltose (AAN).

2 Qualitative and Quantitative Composition

Carton of 5 x 2 mL ampoules, with each 2 mL ampoule containing 318 mg iron polymaltose equivalent to 100 mg iron III (50 mg per mL).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Ferrosig Injection is an aqueous, approximately isotonic solution for intravenous and intramuscular injection. It is a slightly viscous, dark reddish-brown liquid. Free of obvious contamination.
Ferrosig Injection contains a macromolecular spherocolloidal complex of iron (III) hydroxide and the carbohydrate polymaltose. Iron polymaltose is also considered to be a complex of ferric hydroxide and isomaltose.
Each 2 mL ampoule of Ferrosig Injection contains the equivalent of 100 mg of iron. The aqueous colloidal solution is sterile, pyrogen-free and approximates the pH and tonicity of the tissues.
The excipients are water for injections and hydrochloric acid or sodium hydroxide (for pH adjustment).

4 Clinical Particulars

4.1 Therapeutic Indications

Ferrosig is indicated for the treatment of iron deficiency anaemia in the following circumstances:
When oral therapy is contraindicated.
When enteric absorption of iron is defective.
When patient noncompliance or persistent gastrointestinal intolerance makes oral therapy impractical.

4.2 Dose and Method of Administration

Intramuscular use.

Technique of injection.

The technique of injection is of crucial importance.
Ferrosig Injection should never be injected into the arm or other exposed areas. The wrong injection technique may result in pain and persistent discolouration of the skin.
The following method of ventrogluteal injection according to Hochstetter is recommended instead of the normal method of injection in the top outer quadrant of the gluteus maximus muscle. (See manufacturer's product information for diagrams.)
a. The length of the needle should be at least 5-6 cm. The lumen of the needle should not be too wide.
b. The site of injection is determined as follows. First point A is found, corresponding to the ventral iliac spine. If the patient lies on the right side, for instance, the middle finger of the left hand is placed on point A. The index finger is extended away from the middle finger, so that it comes to lie below the iliac crest, at point B. The triangle lying between the proximal phalanges of the middle and index fingers represents the site of injection. This is disinfected in the usual way.
c. Before the needle is inserted, the skin over the site of injection is pulled down, about 2 cm, to give an S shaped puncture channel. This prevents the injected solution from running back into the subcutaneous tissues and discolouring the skin.
d. The needle is introduced more or less vertically to the skin surface, angled to point towards the iliac crest rather than the hip joint.
e. After the injection, the needle is slowly withdrawn and pressure from a finger applied beside the puncture site. This pressure is maintained for about one minute.
f. The patient should move about after the injection.

Intravenous use.

Total dose infusion of iron polymaltose complex is recommended only when the intramuscular route is impractical or unacceptable and when bone marrow shows no stored iron. It is suitable for use in hospitals only.
The total dose to be administered, calculated from the dosage table (Table 1), is aseptically added to 500 mL of sterile, normal saline (up to 2,500 mg may be given in 500 mL).

Notes.

1. Do not inject the iron into the tube of the administration set.
2. The first 50 mL should be infused slowly (5-10 drops/minute) and the patient observed carefully. If this is well tolerated, the rate may be increased to 30 drops/minute (based on a drop volume of 0.067 mL).
3. To avoid nausea and epigastric troubles the infusion rate should not be excessive.
4. The infusion should not be mixed with any other therapeutic agents. If mixed with acidic substances or other substances with a strong reducing effect toxic iron compounds may be liberated from the compound.

Calculation of required dose.

The figures in the accompanying dosage table have been calculated using the following formula taken from Ganzoni (Schweiz. med. Wschr. 1970; 100, 301-619). See Equation 1.

Note.

The above formula can also be used to calculate the total iron deficit.
Up to 34 kg bodyweight: target Hb = 130 g/L, iron depot = 15 mg/kg bodyweight (for a patient weighing 34 kg the iron depot is 34 x 15 = 500 mg).
Over 34 kg bodyweight: target Hb = 150 g/L, iron depot = 500 mg.

Example of calculation.

Assuming a patient weighing 60 kg, target Hb 150 g/L, actual Hb 60 g/L and the need for an iron depot of 500 mg then: Hb-iron deficiency = 60 x (150-60) x 0.24 = 1296 mg + 500 mg = 1800 mg iron. Therefore, the patient requires 1800 mg iron or 18 ampoules.

Dosage table.

Dosage for the determination of the total mL of Ferrosig Injection required is shown in Table 1.
Administer 2 mL by intramuscular injection every second day until the total dose is attained or administer 4 mL at longer intervals. Regular determination of Hb level is recommended.

Maximum single daily dose by intramuscular injection.

Infants up to 5 kg bodyweight.

0.5 mL.

Children of 5 to 10 kg bodyweight.

1 mL.

Patients weighing > 10 kg to 45 kg.

2 mL.

Adults.

4 mL.

4.3 Contraindications

Ferrosig Injection should not be given to patients presenting with any of the following conditions:
Hypersensitivity to iron (III) hydroxide polymaltose complex.
Anaemia not caused by simple iron deficiency (e.g. haemolytic anaemia, megablastic anaemia caused by vitamin B12 deficiency, disturbances in erythropoiesis, hypoplasia of the marrow).
Iron overload (e.g. haemochromatosis, haemosiderosis).
Chronic polyarthritis.
Bronchial asthma.
Infectious renal complaints in acute phase.
Uncontrolled hyperparathyroidism.
Decompensated hepatic cirrhosis.
Infectious hepatitis.
During the first trimester of pregnancy.
As elemental iron tends to accumulate in inflamed tissues parenteral iron should not be given to patients with severe inflammation or infection of the kidney or liver.

4.4 Special Warnings and Precautions for Use

Hypersensitivity and anaphylactoid reactions.

There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arteriospasm that can result in myocardial infarction).
Parenterally administered iron preparations can cause hypersensitivity reactions including anaphylactoid reactions, which may be potentially fatal. Therefore facilities for cardio-pulmonary resuscitation must be available. If allergic reactions or signs of intolerance occur during administration, the treatment must be stopped immediately.
It is recommended that patients be monitored during and after Ferrosig administration for at least 30 minutes.
Initial test doses may still be carried out, but this is no longer required as a test dose without incident does not indicate that subsequent doses will also be reaction free.
Since parenteral use of complexes of iron and carbohydrates has resulted in fatal anaphylactoid reactions, iron polymaltose should be used only in patients in whom a clearly established indication for parenteral iron therapy exists, confirmed by appropriate laboratory tests.
Anaphylactoid reactions occur most frequently within the first several minutes of administration and are generally characterised by sudden onset of respiratory difficulties, tachycardia and hypotension. An initial test dose of 25 mg of iron polymaltose should be given prior to the first therapeutic dose of the drug. Adrenaline and facilities for the cardiopulmonary resuscitation must be available. In the case of a mild allergic reaction, administer antihistamines.
Patients with bronchial asthma, low iron binding capacity or folic acid deficiency are particularly at a risk of an allergic or anaphylactoid reaction. Caution is also recommended in patients with a history of allergic disorders, hepatic insufficiency or cardiovascular disease.
Patients with rheumatoid arthritis and possibly other inflammatory diseases (e.g. ankylosing spondylitis, lupus erythematosus) may be at particular risk of delayed reactions, including fever and exacerbation or reactivation of joint pain.
Iron may increase the pathogenicity of certain microorganisms. The use of intramuscular iron in neonates has been associated with an increased incidence of Gram negative sepsis, principally infections caused by E. coli.
Unwarranted administration of parenteral iron preparations may cause excess storage of iron and a syndrome similar to haemosiderosis in patients whose anaemia is not attributable to iron deficiency e.g. those with haemoglobulinopathies.

Use in the elderly.

No data available. For use in elderly, patients should consult a medical practitioner.

Paediatric use.

No data available.

Effects on laboratory tests.

Please see Section 4.8, Laboratory test interferences.

4.5 Interactions with Other Medicines and Other Forms of Interactions

As with all parenteral iron preparations, Ferrosig Injection ampoules should not be administered concomitantly with oral iron preparations as the absorption of oral iron is reduced.
Oral iron therapy should not commence until at least one week after the last iron injection.
Concomitant administration of angiotensin converting enzyme (ACE) inhibitors may increase the incidence of adverse effects associated with parenteral iron preparations, e.g. erythema, abdominal cramps, nausea, vomiting and hypotension.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
Foetal bradycardia may occur following administration of parenteral irons. It is usually transient and a consequence of a hypersensitivity reaction in the mother. The unborn baby should be carefully monitored during administration of parenteral irons to pregnant women.
Ferrosig should only be used in pregnancy if the benefits outweigh the risk due to the risk of anaphylaxis.
Ferrosig Injection should not be administered in the first trimester of pregnancy. No controlled studies are available on animals or on pregnant women.
Ferrosig Injection should only be administered in the second and third trimester of pregnancy if the benefits of treatment outweigh the potential risk to the foetus.
Australian categorisation definition of Category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have shown evidence of an increased occurrence of foetal damage, the significance of which is considered uncertain in humans.
 No data available.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Kounis Syndrome - frequency not known.
In pregnancy, associated foetal bradycardia may occur with parenteral iron preparations.
Adverse reactions to parenteral Ferrosig Injection have only been reported infrequently. However, the following reactions are known to have occurred after parenteral iron therapy:

General.

Flushing, sweating, chills and fever; chest and back pain.
Following intramuscular injection: pain at injection site; local inflammation with inguinal lymphadenopathy; lower quadrant abdominal pain.

Hypersensitivity.

Anaphylaxis.

Gastrointestinal.

Nausea and vomiting.

Central nervous system.

Headache; dizziness.

Musculoskeletal.

Joint and muscle pain; arthralgia; sensation of stiffening of the arms, legs or face; hypophosphataemia including hypophosphataemic osteomalacia.

Cardiovascular.

Faintness; syncope; tachycardia; hypotension; circulatory collapse.

Respiratory.

Bronchospasm with dyspnea.

Haematological.

Generalised lymphadenopathy.

Dermatological.

Rash; urticaria; angioneurotic oedema.
Adverse reactions may be delayed by 1-2 days after treatment with Ferrosig Injection.

Laboratory test interferences.

Large intravenous doses (250 mg or more of iron) of Ferrosig Injection may cause serum from blood samples obtained 4 hours after administration of the drug to have a brown colour. The drug may cause falsely elevated values of serum bilirubin and falsely decreased values of serum calcium. Serum iron determinations (especially colorimetric assays) may not be meaningful for 3 weeks following the administration of the drug. Results of serum iron measurements obtained within 1-2 weeks of administration of large doses of the drug should be interpreted with caution.
Examination of the bone marrow for iron stores may not be meaningful for prolonged periods following treatment as Ferrosig Injection may remain in the reticuloendothelial cells.
Bone scans with technetium Tc 99m diphosphonate, taken 1-6 days after intramuscular injection of the drug may show dense areas of activity in the buttock, following the contour of the iliac crest. Bone scans using imaging agents labelled with technetium Tc 99m, in the presence of high serum ferritin concentrations or following intravenous infusions of the drug, may show reduced bone uptake, marked renal activity, and excessive blood pool and soft tissue accumulation.
The drug may cause a decrease in Ga-67 gallium citrate uptake during tumor and/or abscess imaging with Ga-67 gallium citrate due to competition for the same binding sites.
The presence of iron may give false-positive orthotolidine test results.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdosage of iron causes haemosiderosis and consequent cirrhosis of the liver, diabetes and heart failure. Periodic monitoring of serum ferritin may be useful in recognising a deleterious, progressive accumulation of iron.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The intended pharmacological action of iron polymaltose is to provide utilisable iron to target tissues. Iron polymaltose delivers iron across enterocytes to the iron transport protein transferrin and the iron storage protein ferritin. This iron is subsequently incorporated into haemoglobin during synthesis of red blood cells and thus facilitates correction of iron deficiency and anaemia.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

When injected intramuscularly the iron polymaltose evokes a local inflammatory response and is transported via the lymphatics to the regional lymph nodes without being broken down (reactive absorption). It then enters the blood, reaching its maximum concentration in about 24 hours. The circulating iron polymaltose is taken up by the cells of the reticuloendothelial system, which slowly ionise it to Fe3+ and polymaltose. The majority of Fe3+ is bound to transferrin and transported to the bone marrow where it is incorporated into haemoglobin, the remainder is contained within the storage forms, haemosiderin and ferritin, or incorporated into myoglobin or haem containing enzymes. Only very small amounts of iron are excreted. The conservation of body iron and the lack of an excretory mechanism for excess iron may lead to iron overload if iron intake is excessive. Polymaltose is either metabolised or excreted.
A study was conducted on 12 anaemic women aged from 20 to 45 years. After an intravenous infusion of 100 mg elemental iron, comprising 2 mL of Ferrosig Injection diluted in 48 mL 0.9% sodium chloride, at a rate of 1.7 mL/minute (i.e. 50 mL per 30 minutes) a mean Cmax (in serum) of 25.1 microgram/mL iron was observed. The mean Tmax was 0.75 hours and the mean terminal half-life 22.4 hours. The mean residence time (MRT) was 20.2 hours.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

The excipients are water for injections and hydrochloric acid or sodium hydroxide (for pH adjustment).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the ARTG. The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store in the original package. Store below 25°C. Do not freeze. Protect from light.

6.5 Nature and Contents of Container

Cartons of 5 x 2 mL ampoules, with each ampoule containing 318 mg iron polymaltose equivalent to 100 mg iron III (50 mg per mL).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

The substance has an empirical formula of C120H220O156Fe37 and the complex has a molecular weight of 462,000.
Iron polymaltose, the active substance of Ferrosig, is a macromolecular complex in which polynuclear iron(III)-hydroxide is stabilized by polymaltose. It contains about 53% (m/m)* iron(III)-hydroxide, equivalent to about 27% (m/m) of iron, about 36% (m/m) polymaltose ligand, less than 6.4% (m/m) sodium chloride and less than 10% (m/m) of water.
*Mass fraction mass/mass.

CAS number.

53858-86-9.

7 Medicine Schedule (Poisons Standard)

Poisons Schedule: S4.

Summary Table of Changes