Consumer medicine information

Venofer

Iron sucrose

BRAND INFORMATION

Brand name

Venofer

Active ingredient

Iron sucrose

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Venofer.

What is in this leaflet

This leaflet answers some common questions about VENOFER.

It does not contain all the available information. It does not take the place of talking to your doctor.

All medicines have risks and benefits.

Your doctor has weighed the risks of you being given VENOFER against the benefits they expect it will have for you.

If you have any concerns about receiving VENOFER ask your doctor.

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

What VENOFER is used for

VENOFER provides a source of iron that can help to replenish a shortage of iron in patients with iron deficiency.

Ask your doctor if you have any questions about why VENOFER has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is only available with a doctor's prescription.

There is no evidence that it is addictive.

Before you are given VENOFER

When you must not be given it

You must not be given VENOFER if:

  • you are known to be sensitive to any of the ingredients of this medicine listed at the end of this leaflet
  • your anaemia is not due to a shortage of iron
  • you are in the first trimester of a pregnancy
  • you have a condition known as haemo-chromatosis (an excess of iron in the body) or a genetic tendency towards this condition.

VENOFER should not be used after the expiry date printed on the label.

If you are not sure whether you should be given VENOFER, talk to your doctor.

Before you are given it

You should be aware that:

  • a blood test should have been carried out to ensure treatment with this medicine is appropriate
  • if you have a history of asthma, eczema or other atopic allergies you are more susceptible to experience allergic reactions
  • intravenous iron preparations can cause severe allergic reactions. These allergic reactions may include chest pain. Tell your doctor immediately if you experience it.

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • you or a blood relative have the condition known as haemochromatosis
  • if you have an infection
  • liver disease.

Tell your doctor if you are pregnant or plan to become pregnant or are breast feeding.

You should be aware that:

  • slow heartbeat may occur in unborn babies whose mothers have been administered intravenous iron due to allergic reactions in the mother.

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

Use in children

The safety and efficacy of VENOFER in children has not been established.

Taking other medicines

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

Some medicines, such as iron tablets and VENOFER may interfere with each other.

These medicines may be affected by VENOFER or may affect how well it works. You may need to take different amounts of your medicine or you may need to take different medicines.

Your doctor has more information on medicines to be careful with or avoid while being given this medicine.

How VENOFER is given

How much is given

Your doctor will decide what dose and for how long you will receive VENOFER. This depends on our response to the treatment. Your doctor may change the dose and frequency of your medicine as your condition changes.

How it is given

VENOFER is a sterile solution which is diluted immediately before use. It is given by intravenous infusion or by slow injection into the venous limb of the dialysis line for haemodialysis patients.

It must not be given by intramuscular or subcutaneous injection.

Your doctor or nurse will prepare this medicine for you.

What to expect

Your doctor may order regular blood tests while you are receiving VENOFER in order to monitor your iron levels.

If you are given too much (overdose)

As VENOFER is given to you under the supervision of your doctor, it is very unlikely that you will be given an overdose.

However, if you experience any side effects after being given VENOFER, tell your doctor or nurse immediately.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are being given VENOFER.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor to answer any questions you may have.

Tell your doctor or nurse if you notice any of the following and they worry you:

  • temporary change in taste (e.g. metallic taste)
  • dizziness, lightheadedness
  • fever, shivering
  • injection site reactions (such as pain, irritation, discolouration, burning, swelling or bruising)
  • nausea
  • fatigue

The above list includes the more common side effects of your medicine.

Tell your doctor or nurse immediately if you notice any of the following:

  • stomach pain, diarrhoea, vomiting
  • constipation
  • headache or migraine
  • muscle pain, cramps
  • irregular heart beat
  • itchy skin and rash
  • unusual weakness or tiredness
  • burning sensation
  • tingling or prickling sensation or numbness
  • anxiety
  • increased sweating
  • easy bruising or bleeding
  • abnormal urine colour
  • dry mouth
  • joint pain
  • pallor

Tell your doctor immediately, or go to Accident and Emergency at your nearest hospital if you notice any of the following symptoms:

  • rapid, shallow breathing
  • cold, clammy skin
  • weak, rapid pulse
  • chest pain
  • dizziness, weakness and fainting
  • convulsions
  • facial swelling
  • difficulty in breathing.

These rare side effects are symptoms of a severe allergic reaction. You may need urgent medical attention.

Tell your doctor if you notice anything else that is making you feel unwell, even if you think the problems are not connected with this medicine and are not referred to in this leaflet. Other side effects not listed above may also occur in some people.

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

After using VENOFER

Storage

Normally, your doctor will get VENOFER from the hospital pharmacy or their consulting rooms. However, if for any reason you take this medicine from the pharmacy to your doctor, it is important to store it in a safe place, away from heat and light, where the temperature stays below 25°C.

The product should not be frozen.

Once the ampoules have been opened they should be used immediately.

Keep it where young children cannot reach it.

Product description

What it looks like

VENOFER is a sterile dark brown, nontransparent aqueous solution contained in a 5 mL glass ampoule.

Available in packs of 5 ampoules.

Ingredients

Active ingredient:

Each 5 mL ampoule contains 100 mg of iron as iron sucrose (iron (III)-hydroxide sucrose complex).

Inactive ingredients:

  • sodium hydroxide
  • water for injections.

VENOFER does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

VENOFER is supplied in Australia by:

Vifor Pharma Pty Ltd
Level 9, 140 William Street
Melbourne VIC 3000
Australia

Exclusive New Zealand distributor:

Pharmacy Retailing (NZ) Limited
trading as Healthcare Logistics
Auckland, New Zealand

Australian registration number:
AUST R 98236

This leaflet was prepared in July 2021.

Published by MIMS October 2021

BRAND INFORMATION

Brand name

Venofer

Active ingredient

Iron sucrose

Schedule

S4

 

1 Name of Medicine

Iron sucrose.

2 Qualitative and Quantitative Composition

Each Venofer 5 mL ampoule contains 20 mg/mL iron as iron sucrose (iron (III) hydroxide sucrose complex) as the active ingredient corresponding to 100 mg iron per 5 mL ampoule.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Concentrated injection for intravenous use.
Venofer is a dark brown, non-transparent, aqueous solution with a pH of 10.5-11.0 and an osmolarity of 1250 mOsmol/L.

4 Clinical Particulars

4.1 Therapeutic Indications

Venofer is indicated for the treatment of iron deficiency anaemia in patients undergoing chronic haemodialysis and who are receiving supplemental erythropoietin therapy.
The diagnosis of iron deficiency must be based on appropriate laboratory tests (e.g. serum ferritin, serum iron, transferrin saturation and hypochromic red cells).

4.2 Dose and Method of Administration

The dosage of Venofer is expressed in terms of mg of iron. Each mL contains 20 mg of iron.
Since a test dose without incident does not indicate that subsequent doses will also be reaction free, test doses may still be carried out but are not required.

Treatment of iron deficiency in haemodialysis patients receiving erythropoietin.

The recommended dosage of Venofer for the treatment of iron deficiency in haemodialysis patients receiving erythropoietin therapy is 100 mg of iron (5 mL of Venofer) delivered intravenously during the dialysis session. Frequency of dosing should not be more than three times per week. Most patients will require a minimum cumulative dose of 1000 mg of iron, administered over 10 sequential dialysis sessions, to achieve a favourable haemoglobin or haematocrit response. Patients may continue to require therapy with Venofer at the lowest dose necessary to maintain target levels of haemoglobin, haematocrit and laboratory parameters of iron storage within acceptable limits.
If no response in haematological parameters is observed after 1 to 2 weeks, the original diagnosis should be reconsidered.

Method of administration.

Venofer must only be administered by intravenous route. This may be by drip infusion or by slow injection directly into the venous line of the dialysis machine.
Ampoules should be visually inspected for sediment and damage before use. Use only those containing a sediment-free and homogenous solution.

Intravenous drip infusion.

For IV infusion, the content of each ampoule must be diluted exclusively in a maximum of 100 mL of 0.9% w/v NaCl, immediately prior to infusion. The infusion should be infused at a rate of 100 mg of iron over a period of at least 15 minutes. Unused diluted solution should be discarded.

Injection into venous line of dialysis machine.

Venofer may be administered during a haemodialysis session directly into the venous line of the dialysis machine at a rate of 1 mL (20 mg iron) undiluted solution per minute (i.e. 5 minutes per ampoule), not exceeding one ampoule of Venofer (100 mg iron) per injection. Discard any unused portion.
Venofer is a strongly alkaline solution and must never be administered by the subcutaneous or intramuscular route.

Note.

Do not mix Venofer with other medication or add to parenteral nutrition solutions for intravenous infusion.

4.3 Contraindications

The use of Venofer is contraindicated in the following conditions:
hypersensitivity to iron sucrose, Venofer or to any of its excipients listed in Section 6.1 List of Excipients;
anaemia not caused by iron deficiency;
iron overload or disturbances in utilisation of iron;
known haemochromatosis or genetic tendency to haemochromatosis;
pregnancy first trimester.

4.4 Special Warnings and Precautions for Use

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 Venofer require periodic monitoring of hematologic and hematinic parameters (haemoglobin, haematocrit, 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.
Parenterally administered iron preparations can cause allergic or anaphylactoid reactions, which can be potentially fatal. There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arteriospasm that can result in myocardial infarction). Therefore, antiallergic treatment should be available along with cardiopulmonary resuscitation facilities and procedures. Hypersensitivity reactions have also been reported after previously uneventful doses of parenteral iron complexes including iron sucrose. Each patient should be observed for adverse effects for at least 30 minutes following each Venofer injection.
There are no data on the safety of Venofer when used in patients who are allergic to iron polymaltose.
In patients with a history of asthma, eczema, other atopic allergies or allergic reactions to other parenteral iron preparations, Venofer should be administered with caution as these patients may be particularly at risk of an allergic reaction.
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. 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 Venofer is stopped in patients with bacteraemia. In patients with chronic infection, a risk/benefit evaluation should be performed.
Hypotension has been reported frequently in hemodialysis patients receiving intravenous iron. Hypotension following administration of Venofer may be related to rate of administration and total dose administered.
Caution should be taken to administer Venofer according to recommended guidelines (see Section 4.2 Dose and Method of Administration).
Care must be taken to avoid paravenous infiltration. If this occurs, the infusion of Venofer should be discontinued immediately. Ice may be applied to cause local vasoconstriction and decrease fluid absorption; massage of the area should be avoided.
Paravenous leakage must be avoided because leakage of Venofer at the injection site may lead to pain, inflammation, sterile abscess and brown discolouration of the skin.

Use in the elderly.

No data available.

Paediatric use.

The safety and efficacy of Venofer in children has not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

As with all parenteral iron preparations, Venofer should not be administered concomitantly with oral iron preparations since the absorption of oral iron is reduced. Therefore, oral iron therapy should be discontinued 24 hours prior to the first injection of iron sucrose and should not be started within 5 days after the last injection of iron sucrose.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Venofer did not affect the fertility of male or female rats when administered thrice weekly at IV doses of up to 15 mg Fe/kg (about 1.4 times the maximum clinical dose based on body surface area (BSA) and weekly dose).
(Category B3)
In pregnant rats, administration of iron sucrose during organogenesis at daily IV doses of 6.5 and 13 mg Fe/kg, was associated with a higher incidence of minor skeletal abnormalities, suggesting delayed development. Developmental effects were associated with maternotoxic doses (1.4-2.8 times the maximum clinical dose, based on BSA and weekly dose). Embryofetal survival was reduced in rats at daily IV doses of 20 mg Fe/kg (or 4.2 times the maximum clinical dose based on BSA and weekly dose).
In pregnant rabbits, administration of iron sucrose during organogenesis at daily IV doses of 13 mg/kg was associated with embryotoxicity. Embryofetal effects were associated with maternotoxicity (5 times the maximum clinical dose, based on BSA and weekly dose). No effects were observed at IV doses up to 6.5 mg Fe/kg/day (2.6 times the maximum clinical dose, based on BSA and weekly dose).
There are no adequate and well-controlled studies in pregnant women. 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 intravenous administration of parenteral irons to pregnant women.
Because animal reproductive studies are not always predictive of human response, Venofer should be used during pregnancy only if the potential benefits justifies the potential risk to the foetus (see Section 4.4 Special Warnings and Precautions for Use) and should not be used in the first trimester (see Section 4.3 Contraindications).
 Iron of Venofer is excreted in the milk of rats. There is insufficient information on the excretion of iron in human milk following administration of intravenous Venofer. A risk of newborns/infants being exposed to iron derived from Venofer via the mother's milk cannot be excluded.

4.7 Effects on Ability to Drive and Use Machines

Venofer is unlikely to influence the ability to drive or use machines.
However, if symptoms such as dizziness, confusion or lightheadedness occur following the administration of Venofer, affected patients should not drive a car or use machines until the symptoms have abated.

4.8 Adverse Effects (Undesirable Effects)

The most frequently reported adverse drug reactions (ADRs) of Venofer in clinical trials were transient taste perversion, hypotension, fever and shivering, injection site reactions and nausea, occurring 0.5 to 1.5% of the patients. Non-serious hypersensitivity reactions occurred rarely.
In general, hypersensitivity reactions are potentially the most serious adverse reactions (see Section 4.4 Special Warnings and Precautions for Use). In pregnancy, foetal bradycardia associated to hypersensitivity in the mother may occur with parenteral iron preparations (see Section 4.6 Fertility, Pregnancy and Lactation).
Table 1 summarises the adverse drug reactions that have been reported in temporal relationship with the administration of Venofer, with at least a possible causal relationship.

Reporting suspected adverse reactions.

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 https://www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdose can cause iron overload which may manifest itself as haemosiderosis.
Overdosage should be treated with supportive measures and, if required, an iron chelating agent.
For the information of the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Venofer is used to replenish body iron levels in patients with iron deficiency on chronic haemodialysis and receiving erythropoietin. In these patients iron deficiency is caused by blood loss during the dialysis procedure, increased erythropoiesis and insufficient absorption of iron from the gastrointestinal tract. Iron is essential to the synthesis of haemoglobin to maintain oxygen transport and to the function and formation of other physiologically important haem and non-haem compounds. Most haemodialysis patients require intravenous iron to maintain sufficient iron levels to achieve and maintain haemoglobin of 11-12 g/dL.

Clinical trials.

The following pivotal studies have compared the use of intravenous (IV) and oral iron in haemodialysis patients receiving erythropoietin. Hussain et al1 assessed the efficacy of IV iron sucrose vs. oral iron supplementation in haemodialysis (HD) patients. This was a single-centre open randomised parallel trial in patients with end stage renal failure on maintenance HD two sessions per week. The primary efficacy outcome was achievement of a target haemoglobin (Hb) concentration of 11-12 g/dL. 20 patients with serum ferritin > 20 nanogram/mL and transferrin saturation > 30% were assigned to one of two groups. Group 1 (n = 10) received 100 mg as IV iron sucrose twice weekly post-dialysis. Group 2 (n = 10) received 200 mg oral ferrous sulfate three times daily. Both groups received subcutaneously (SC) erythropoietin 20 unit/kg bw twice weekly post-dialysis. Following three months of treatment the mean Hb and haematocrit (Hct) was significantly higher in Group 1 than Group 2 (Hb 11.6 ± 0.64 g/dL vs. 10.5 ± 1.14 g/dL, p < 0.01). There was no significant difference in secondary efficacy variables (transferrin saturation, serum ferritin and erythropoietin dose) after three months of treatment.
Erten et al2 compared an intensive IV iron regimen with a maintenance type regimen, with oral supplementation. This was a three group (n = 26, n = 21 and n = 22) randomised parallel study on stable haemodialysis (HD) patients receiving SC erythropoietin 150 unit/kg for at least 3 months. Subjects treated with an intensive IV iron regimen (100 mg x 3 per week for 10 doses, then 100 mg weekly) obtained a higher haemoglobin after 6 months than those treated with oral iron (11.8 vs. 9.8 g/dL) and had a greater reduction in EPO dose (27% vs. 2%). Iron stores were also greater (serum ferritin 573.8 vs. 195.8 nanogram/mL). A statistical analysis of the data was not conducted.
1 Hussain R. Chishti SH; Naqvi SAJ. Experience of iron saccharate supplementation in haemodialysis patients treated with erythropoietin. Nephrology. Vol 4 (1-2) (pp 105-108), 1998.
2 Erten Y., et al.; Comparison of the effect of intravenous and oral iron therapies on haemodialysis patients. XXXV Congress of the Europ. Renal Association/Europ. Dialysis and Transplant Association. 6-9 June 1998, Rimini, Italy.

5.2 Pharmacokinetic Properties

In healthy adults treated with intravenous doses of Venofer, its iron component exhibits first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, nonsteady-state apparent volume of distribution of 10.0 L and steady-state apparent volume of distribution of 7.9 L. Since iron disappearance from serum depends on the need for iron in the iron stores and iron utilising tissues of the body, serum clearance of iron is expected to be more rapid in iron deficient patients treated with Venofer as compared to healthy individuals. The effects of age and gender on the pharmacokinetics of Venofer have not been studied.
The iron sucrose complex is not dialyzable through CA 210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of iron sucrose in the dialysate fluid was below the level of detection of the assay (less than 2 parts per million).

Distribution.

In healthy adults receiving intravenous doses of Venofer, its iron component appears to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Venofer containing 100 mg of iron labelled with 52Fe/59Fe in patients with iron deficiency shows that a significant amount of the administrated iron distributes in the liver, spleen and bone marrow and that the bone marrow is an iron trapping compartment and not a reversible volume of distribution.

Metabolism and excretion.

Following intravenous administration of Venofer, iron sucrose is dissociated into sucrose and the polynuclear iron core, which is taken up by the macrophages of the reticuloendothelial system. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Venofer containing 1510 mg of sucrose and 100 mg of iron in 12 healthy adults (9 female, 3 male; age range 32-52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration3. In this study and another study evaluating a single intravenous dose of iron sucrose containing 500-700 mg of iron in 26 anemic patients on erythropoietin therapy (23 female, 3 male; age range 16-60), approximately 5% of the iron was eliminated in urine in 24 h at each dose level4.
3 Danielson B., et al.; Pharmacokinetics of Iron(III)-Hydroxide Sucrose Complex after a Single Intravenous Dose in Healthy Volunteers, Drug Research 46: 615-621, 1996.
4 Anatkov A. Gekova K.; Problems of Hem. Bld. Transfusions, Med. Physioculture, 13: 295-298, 1970.

5.3 Preclinical Safety Data

Carcinogenicity.

No long-term studies in animals have been performed to evaluate the carcinogenic potential of iron sucrose.

Genotoxicity.

Iron sucrose was not genotoxic in assays for gene mutation (in vitro bacterial and mouse lymphoma cell assays) and chromosomal damage (human lymphocytes in vitro and mouse micronucleus test in vivo).

6 Pharmaceutical Particulars

6.1 List of Excipients

The excipients are water for injections and sodium hydroxide for pH adjustment.

6.2 Incompatibilities

Venofer must not be mixed with other medicinal products except sterile 0.9% m/V sodium chloride (NaCl) solution. There is the potential for precipitation and/or interaction if mixed with other solutions or medicinal products. The compatibility with containers other than glass, polyethylene and PVC is not known.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
Shelf-life after first opening of the container and after dilution with sterile 0.9% m/V sodium chloride (NaCl) solution: from a microbiological point of view, the product should be used immediately.
Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.

6.4 Special Precautions for Storage

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

6.5 Nature and Contents of Container

5 mL solution in one ampoule (Type I glass) in pack sizes of 5.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Venofer solution contains a mixture of polymers, each consisting of a polynuclear iron (III) hydroxide core superficially surrounded by a larger number of non-covalently bound sucrose molecules.
The proposed molecular formula is: [Na2Fe5O8(OH).3(H2O)]n.m(C12H22O11) where n is the degree of iron polymerization and m is the number of sucrose molecules associated with the iron (III)-hydroxide.
Molecular weight range: 34,000-60,000.
Nominal amount of sucrose: 320 g/L.

CAS number.

8047-67-4 (saccharated iron oxide).

7 Medicine Schedule (Poisons Standard)

S4 (Prescription only medicine).

Summary Table of Changes