Ferinject (ferric carboxymaltose)

• Section 2 and 3 - formulation changed from solution to dispersion.
• Section 4.2 - dosing guidance added for children and adolescents aged 1 to 13 years.
• Section 4.4 - 'anaphylactoid' reactions removed under hypersensitivity reactions and only anaphylactic reactions listed. Sentence removed saying Ferinject has not been studied in children.
• Section 4.8 - table of ADRs now represents >9000 (previously 8000) patients including >100 children and adolescents aged 1 to 17 years. Some formatting changes to table 4. MHRA Yellow card scheme website link updated URL.
• Section 5.1 - studies added on use of Ferinject in paediatric population.
• Section 5.2 - pharmacokinetic information for paediatric population added.
• Section 6.5 - formulation changed from solution containing iron to dispersion.
• Section 6.6 - formulation changed to dispersion.
• section 10: date of revision: April 2023

• formulation changed from solution to dispersion.
• dosing guidance added for children and adolescents aged 1 to 13 years.
• "anaphylactoid " reactions removed under hypersensitivity reactions and only anaphylactic reactions listed. Sentence removed saying Ferinject has not been studied in children.
• date of revision: February 2023

Text revision date has been updated to February 2022

Text revision date has been updated to February 2022

the black symbol and the related statement in the product information removed.

the black symbol and the related statement in the product information removed

Editorial Amendment of SmPC Section 2 to state the active substance name ferric carboxymaltose consistently with other parts of the product information.

Information update regarding the excipient sodium in SmPC Section 4.4 in line with the current European Commission guideline on ’’Excipients in the labelling and package leaflet of medicinal products for human use”

QUALITATIVE AND QUANTITATIVE COMPOSITION
One mL of solution contains ferric carboxymaltose corresponding to 50 mg iron.
Each 2 mL vial contains ferric carboxymaltose corresponding to 100 mg iron.
Each 10 mL vial contains ferric carboxymaltose corresponding to 500 mg iron.
Each 20 mL vial contains ferric carboxymaltose corresponding to 1,000 mg iron.

Excipients
Ferinject contains up to 5.5 mg (0.24 mmol) sodium per mL of undiluted solution, equivalent to 0.3% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Information update regarding the excipient sodium in PIL Section 2 in line with the current European Commission guideline on ’’Excipients in the labelling and package leaflet of medicinal products for human useInformation update regarding the excipient sodium in SmPC Section 4.4 and PIL Section 2 in line with the current European Commission guideline on ’’Excipients in the labelling and package leaflet of medicinal products for human use

' Ferinject contains sodium
This medicine contains up to 5.5 mg sodium (main component of cooking/table salt) in each mL of undiluted solution. This is equivalent to 0.3% of the recommended maximum daily dietary intake of sodium for an adult.'

Date of revision updated to August 2021

Addition of 'distant skin discolouration' within AE table under 

4.8 addtion of ' and skin discoloration at other areas of the body than the administration site.'

Section 6 updated following brexit : This medicine is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names: UK(NI) etc

Date of revision changed to Jan 2021

Date of revision changed to Jan 2021

Added: Tell your doctor if you develop worsening of tiredness, muscle or bone pain (pain in your arms or legs, joints or back). That may be a sign of a decrease in blood phosphorus which might cause your bones to become soft (osteomalacia). This condition may sometimes lead to bone fractures. Your doctor may also check the levels of phosphate in your blood, especially if you need a number of treatments with iron over time.

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.

Please also note the below side effects have been updated from frequency ‘rare’ to frequency ‘unknown’;

Nervous system disorders (frequency unknown) - Loss of consciousness

Skin and subcutaneous tissue disorders  (frequency unknown) - face oedema

The following changes were approved within the SmPC and are highlighted in the blue text below:

1) Section 4.1: new indication “when there is a clinical need to deliver iron rapidly”

2) Section 4.2: minor editorial change in safety section

3) Section 5.1: Study EFFECT-HF

section 1: Ferinject is a medicine that contains iron.

Medicines that contain iron are used when you do not have enough iron in your body. This is called iron deficiency.

Ferinject is used to treat iron deficiency when:

• oral iron is not effective enough.
• you cannot tolerate oral iron.
• your doctor decides you need iron very quickly to build up your iron stores.

The doctor will determine whether you have iron deficiency by performing a blood test.

section 2: ( part removed from here and placed below)

section 3: How Ferinject is administered

Your doctor will decide how much Ferinject to give you, how often you need it and for how long. Your doctor will perform a blood test to determine the dose you need. Your doctor or nurse will administer Ferinject undiluted by injection, during dialysis, or diluted by infusion:

Ferinject will be administered in a structure where immunoallergic events can receive appropriate and prompt treatment. You will be observed for at least 30 minutes by your doctor or nurse after each administration.

If you receive more Ferinject than you should

As this medicine will be given to you by trained medical staff it is not likely that you will be given too much of this medicine

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.

Vifor Pharma UK Limited

The Old Stables, Bagshot Park, Bagshot, Surrey, GU19 5PJ UK

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.

Vifor Pharma UK Limited

The Old Stables, Bagshot Park, Bagshot, Surrey, GU19 5PJ UK

Foetal bradycardia. 

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

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.

4.2 - Posology and method of administration:

• Special population: "injection" removed.
• Table 3 Dilution Plan of Ferinject for intravenous infusion - added "no minimal prescribed time" to minimum administration time.

4.4 Special Warnings and Precautions for use:

• Added paragraph on Hypophosphataemia.
• Extravasation: "injection" replaced with administration.

4.5 Interaction with other medicinal products and other forms of interaction:

• "injection" replaced with administration.

4.8 Undesirable effects:

• "7,391" replaced with >8,000.

• Paragraph re worded from: "The most commonly reported ADR is nausea (occurring in 2.9% of the subjects), followed by injection/infusion site reactions, hypophosphataemia, headache, flushing, dizziness and hypertension. Injection/infusion site reactions comprise several ADRs which individually are either uncommon or rare. In clinical trials, the minimum serum phosphorous values were obtained after approximately 2 weeks, and 4 to 12 weeks following Ferinject treatment the values had returned to those within the range of baseline. The most serious ADR is anaphylactoid reactions (rare)." to: "For subjects in clinical trials that showed a decrease in serum phosphorous, the minimum values were obtained after approximately 2 weeks, and in most cases returned to baseline values by 12 weeks following Ferinject treatment . The most serious ADR is anaphylactoid/anaphylactic reactions (rare); fatalities have been reported. See section 4.4 for further details.

• Table 4: "Anaphylactoid reactions" replaced with Anaphylactoid/anaphylactic reactions. Added (whose onset may vary from a few hours to several days) following "Malaise,influenza like illness".  Table footnote: 2. "were" replaced with are. 4. added: but is not limited to.

5.1 Pharmacodynamic properties:

• Cardiology: Abbriviation "(CHF)" removed.

The following changes have been made in section 4.2 (Posology and method of administration):

·              In the second paragraph the word ‘injection’ has been replaced with ‘administration’

·              Table 1 (Determination of the iron need) has been updated to reflect changes to the symbols in columns 1 and 2 and the wording in column 5.

In the third paragraph in section 4.4 (Special warnings and precautions for use) the word ‘injection’ has been replaced with ‘administration’

In section 4.6 (Fertility, pregnancy and lactation) the wording ‘no adequate and well controlled trials’ has been replaced with ‘limited data for the use’

The following changes have been made in section 4.8  (undesirable effects):

·              The number of subjects listed in paragraph 1 has been updated from ‘6755’ to ‘7391’

·              The wording in paragraph 2 has changed from:

The most commonly reported ADR is nausea (occurring in 3.1% of the patients), followed by headache, dizziness, and hypertension. Injection site reactions categorised as common in Table 4 are comprised of several ADRs which individually have been reported with a frequency of either uncommon or rare. Hypophosphataemia (common) may occur. In clinical trials the minimum values were obtained after approximately 2 weeks, and 4 to 12 weeks following Ferinject treatment the values had returned to those within the range of baseline. The most serious ADR is anaphylactoid reactions with a frequency of rare. 

To:

The most commonly reported ADR is nausea (occurring in 2.9% of the subjects), followed by injection/infusion site reactions, hypophosphataemia, headache, flushing, dizziness and hypertension. Injection/infusion site reactions comprise several ADRs which individually are either uncommon or rare. In clinical trials, the minimum serum phosphorous values were obtained after approximately 2 weeks, and 4 to 12 weeks following Ferinject treatment the values had returned to those within the range of baseline. The most serious ADR is anaphylactoid reactions (rare).

·              Table 4 (Adverse drug reactions observed during clinical trials and post-marketing experience) has been updated. Rigors has been removed, pain in extremity has been added as uncommon, flushing is now listed as common, alanine aminotransferase increased is now listed as uncommon.

The following changes have been made in section 5.1 (Pharmacodynamic properties):

·              In the second paragraph and under the subheadings ‘Nephrology, Gastroenterology and Women’s health’ the word ‘patients’ has been replaced with ‘subjects’

·              The clinical trial data under the subheadings ‘Cardiology and Pregnancy’ have been updated

·              Under the subheading ‘Gastroenterology’ the Study number has been amend from ‘Study VIT-CL-IV-008’ to Study ‘VIT-IV-CL-008’

In section 5.2 (Pharmacokinetic properties) the word ‘patients’ has been replaced with ‘subjects’

In section 10 (Date of Revision of the text) has been updated to ‘April 2017’

7. MARKETING AUTHORISATION HOLDER

Has changed from

Vifor France SA
7-13, Boulevard Paul-Emile Victor
92200 Neuilly-sur-Seine
France
Tel. +33 (0)1 41 06 58 90
Fax +33 (0)1 41 06 58 99 

To

Vifor France
100-101 Terrasse Boieldieu
Tour Franklin La Défense 8
92042 Paris La Défense Cedex
France
Tel.  +33 (0)1 41 06 58 90
Fax  +33 (0)1 41 06 58 99

10. DATE OF REVISION OF THE TEXT

Section 4.1

The diagnosis of iron deficiency must be based on laboratory tests

Section 4.2

Typographical changes to facilitate ease of interpretation:

The posology of Ferinject follows a stepwise approach:

1- determination of the individual iron need

2- calculation and administration of the iron dose(s)

3- post-iron repletion assessments.

Section 4.4

Sub-headings added to categorize nature of warnings and precautions

Section 4.5

The absorption of oral iron is reduced when administered concomitantly with parenteral iron preparations. Therefore, if required, oral iron therapy should not be started for at least 5 days after the last injection of Ferinject.

Section 4.6

Clinical studies showed that transfer of iron from Ferinject to human milk was negligible (≤1%). Based on limited data on breast-feeding women it is unlikely that Ferinject represents a risk to the breast-fed child

Section 4.8

Inclusion of “influenza like illness” as a rare adverse drug reaction

Section 5.1

Inclusion of the following data:

Ferritin monitoring after replacement therapy

There is limited data from study VIT-IV-CL-008 which demonstrates that ferritin levels decrease rapidly 2-4 weeks following replacement and more slowly thereafter. The mean ferritin levels did not drop to levels where retreatment might be considered during the 12 weeks of study follow up. Thus, the available data does not clearly indicate an optimal time for ferritin retesting although assessing ferritin levels earlier than 4 weeks after replacement therapy appears premature.  Thus, it is recommended that further re-assessment of ferritin should be made by the clinician based on the individual patient’s condition.

Section 6.4

Store in the original package in order to protect from light. Do not store above 30 °C. Do not freeze

Section 6.5

Typographical changes ml to mL

Section 10

Date of revision of text has been update to September 2015

Change to

5.1 Pharmacodynamic properties

From:
Pharmacotherapeutic group: Iron trivalent, parenteral preparation, ATC code: B03A C01

To:
Pharmacotherapeutic group: Iron trivalent, parenteral preparation, ATC code: B03AC

In section 2

“Each 20 mL vial contains 1000 mg of iron as ferric carboxymaltose.” Has now been added.
volumes are now listed in mL

In section 4.2

“For doses up to 200 mg iron, there is no prescribed administration time.” Has now been added under “Intravenous injection”

The term “intravenous drip infusion” has now been replaced with “intravenous infusion”

Dilution plan of Ferinject for intravenous infusion has been clarified to confirm which dose ranges require what volume of sterile 0.9% m/V sodium chloride solution.

In section 4.8

The following text has been incorporated:

“The most commonly reported ADR is nausea (occurring in 3.1% of the patients), followed by headache, dizziness, and hypertension. Injection site reactions categorised as common in Table 3 are comprised of several ADRs which individually have been reported with a frequency of either uncommon or rare. Hypophosphataemia (common) may occur. In clinical trials the minimum values were obtained after approximately 2 weeks, and 4 to 12 weeks following Ferinject treatment the values had returned to those within the range of baseline. The most serious ADR is anaphylactoid reactions with a frequency of rare.”

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 revised.

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 10

Dates of revision has been updated

In section 4.2

Details on post-dose monitoring have been included.

In section 4.3

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

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

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

This section has been revised and re-written for clarity

In section 4.8

Details of the reporting authority have been included

In section 10

Dates of revision has been updated