Venofer (iron sucrose)

Venofer 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.

Venofer 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.

Venofer 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.

Venofer 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.

Removal of 2.5 ml vials

Removal of 2.5 ml vials

Section 6 - contents of the pack and other information has been updated to remove the local representative from the PIL, highlighted in blue in the text below.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

Vifor Pharma UK Limited
The Old Stables, Bagshot Park
Bagshot
Surrey
GU19 5PJ
United Kingdom
Tel: +44 1276 853600
Fax: +44 1276 452341

Sections 4.4 Special warnings and precautions for use and 4.8 undesirable effects table have been updated to include additional wording regarding Kournis syndrome and is highlighted in the blue text below.

Sections 4.4 Special warnings and precautions for use and 4.8 undesirable effects table have been updated to include additional wording regarding Kournis syndrome and is highlighted in the blue text below.

 Sections 4.4 Special warnings and precautions for use and 4.8 undesirable effects table have been updated to include additional wording regarding Kournis syndrome and is highlighted in the blue text below.

Section 4.6 Fertility, pregnancy and lactation has been updated to include additional wording regarding foetal bradycardia and is highlighted in the blue text below.

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.

Addition of ADR influenza like illness and amendment of anaphylactoid reactions to anaphylactoid/anaphylactic reactions.

Anaphylactoid/anaphylactic reactions were reported only in the post-marketing setting (estimated as rare); fatalities have been reported. See section 4.4.

4.2       Posology and method of administration

The patient should be observed for adverse effects for at least 30 minutes following each Venofer administration

4.4       Special warnings and precautions for use

Paravenous leakage must be avoided because leakage of Venofer at the injection site can lead to pain, inflammation and brown discoloration of the skin

4.8       Undesirable effects

Changes to the frequency and  terminology around certain adverse events

10                    Date of Revision of the Text

August 2016

4   Clinical Particulars

4.1  Therapeutic Indications

in chronic kidney disease when oral iron preparations are less effective.

has been changed to

in chronic kidney disease when oral iron preparations are less effective than venofer.

10 Date of Revision of the Text

Is now April 2016

4.6 Fertility, pregnancy and lactation

Fertility

No effects of iron sucrose treatment were observed on fertility and mating performance in rats.

10 DATE OF REVISION OF THE TEXT

February 2016

In section 4.2

Section has been revised for clarrification

In section 4.3

Typographical changes

In section 4.4

The following text has been incorporated:

 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, Venofer was shown to be well tolerated. For known serious hypersensitivity to other parenteral iron product see section 4.3.

The risk is enhanced for patients with known allergies including drug allergies, including patients with a history of severe asthma, eczema or other atopic allergy.

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

Paravenous leakage must be avoided because leakage of Venofer at the injection site can lead to pain, inflammation, tissue necrosis and brown discoloration of the skin

In section 4.6

The following text has been incorporated:

There is no data from the use of iron sucrose in pregnant women in the first trimester. Data (303 pregnancy outcomes) from the use of Venofer in pregnant women in the second and third trimester showed no safety concerns for the mother or newborn.

A careful risk/benefit evaluation is required before use during pregnancy and Venofer should not be used during pregnancy unless clearly necessary (see section 4.4).

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Breast-feeding

There is limited information on the excretion of iron in human milk following administration of intravenous iron sucrose. In one clinical study, 10 healthy breast-feeding mothers with iron deficiency received 100 mg iron in the form of iron sucrose. Four days after treatment, the iron content of the breast milk had not increased and there was no difference from the control group (n=5). It cannot be excluded that newborns/infants may be exposed to iron derived from Venofer via the mother’s milk, therefore the risk/benefit should be assessed

Preclinical data do not indicate direct or indirect harmful effects to the nursing child. In lactating rats treated with 59Fe-labelled iron sucrose, low secretion of iron into the milk and transfer of iron into the offspring was observed. Non metabolised iron sucrose is unlikely to pass into the mother’s milk.

In section 4.8

The following text has been incorporated:

The most commonly reported adverse drug reaction in clinical trials with Venofer was dysgeusia, which occurred with a rate of 4.5 events per 100 subjects. The most important serious adverse drug reactions associated with Venofer 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 Venofer in 4,046 subjects in clinical trials as well as those reported from the post-marketing setting are presented in the table below.

Hypertension and hypophosphataemia are now listed as “common”

Dysgeusia, tachycardia, dyspnoea, abdominal pain, constipation, diahorrea, , erythema, rash, muscle spasms and chills are now “uncommon”

Anaphylactoid reactions, loss of consciousness, anxiety, syncope, presyncope, bronchospasm, flatulence, angioedema, pallor, and face oedema, rigors, malaise are now “rare”.

Detail on how to report Adverse events have also been included.

In section 4.9

Overdose can cause iron overload which may manifest itself as haemosiderosis. Overdose should be treated, as deemed necessary by the treating physician, with an iron chelating agent or according to standard medical practice.

In section 5.1

Data has been added on clinical efficacy and safety on Ferinject in in different therapeutic areas necessitating intravenous iron to correct iron deficiency.

In section 5.2

The acronym for Positron emission tomography has been removed

An acronym for iron deficiency has been added.

In section 5.3

 Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity and toxicity to reproduction and development

In section 6.1

Sodium hydroxide (for pH adjustment)

In section 6.2

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6. 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.

In section 6.4

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

For storage conditions after dilution or first opening of the medicinal product, see section 6.3.

In section 6.6

Vials should be visually inspected for sediment and damage before use. Use only those containing a sediment free and homogenous solution.

Venofer 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 section 4.2.

The diluted solution must appear as brown and clear.

Each vial of Venofer is intended for single use only.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

In section 10

Dates of revision has been updated

In section 4.2

The following wording has now been included

“Monitor carefully patients for signs and symptoms of hypersensitivity reactions during and following each administration of Venofer.

Venofer 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 Venofer injection (see section 4.4).”

All references to the test dose have been removed.

In section 4.3

“hypersensitivity to the active substance, to Venofer or any of its excipients listed in section 6.1.” has replaced “known hypersensitivity to Venofer or to any of its excipients”

“known serious hypersensitivity to other parenteral iron products.” Has been added

The following contraindications have been removed:

• patients with a history of asthma, eczema or other atopic allergy, because they are more susceptible to experience allergic reactions

• pregnancy first trimester.

In section 4.4

The following text has been incorporated:

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.

The risk 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).

Ferinject should only be administered when staff trained to evaluate and manage anaphylactic reactions are 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 Ferinject 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 1:1000 adrenaline solution. Additional treatment with antihistamines and/or corticosteroids should be given as appropriate.

In section 4.6

The following text has been incorporated:

“There are no adequate and well-controlled trials of Venofer in pregnant women. A careful risk/benefit evaluation is therefore required before use during pregnancy and Venofer should not be used during pregnancy unless clearly necessary (see section 4.4).

Iron deficiency anaemia occurring in the first trimester of pregnancy can in many cases be treated with oral iron. Treatment with Venofer should be confined to second and third trimester if the benefit is judged to outweigh the potential risk for both the mother and the foetus.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Data on a limited number of exposed human pregnancies indicated no adverse effects of Venofer on pregnancy or on the health of the foetus/newborn child.”

The following test has been removed:

Data on a limited number of exposed pregnancies indicated no adverse effects of Venofer 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.

Venofer 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.

In section 4.8

The following text has been incorporated:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the national reporting system listed in Appendix V.

In section 10

Dates of revision has been updated