Ferinject 50 mg Fe/ml Injektions-/infusionsvätska, lösning

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

Bipacksedel Bipacksedel (PIL)

19-11-2020

Produktens egenskaper Produktens egenskaper (SPC)

03-01-2019

Aktiva substanser:
järn(III)karboximaltos
Tillgänglig från:
Orifarm AB
ATC-kod:
B03AC
INN (International namn):
iron (III) karboximaltos
Dos:
50 mg Fe/ml
Läkemedelsform:
Injektions-/infusionsvätska, lösning
Sammansättning:
järn(III)karboximaltos 180 mg Aktiv substans
Receptbelagda typ:
Receptbelagt
Bemyndigande status:
Avregistrerad
Godkännandenummer:
55339
Tillstånd datum:
2017-03-29

Dokument på andra språk

Bipacksedel Bipacksedel - engelska

07-09-2021

Produktens egenskaper Produktens egenskaper - engelska

07-09-2021

Läs hela dokumentet

210611_PIL-YV007/YV080/YV013/MR/E27

Package leaflet: Information for the patient

Ferinject 50 mg iron/mL solution for injection/infusion

Ferric carboxymaltose

This medicine is subject to additional monitoring. This will allow quick identification of new

safety information. You can help by reporting any side effects you may get. See the end of section 4

for how to report side effects.

Read all of this leaflet carefully before you are given this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor.

If you get any side effects, talk to your doctor. This includes any possible side effects not listed

in this leaflet. See section 4.

What is in this leaflet

What Ferinject is and what it is used for

What you need to know before you receive Ferinject

How Ferinject is given

Possible side effects

How to store Ferinject

Contents of the pack and other information

1.

What Ferinject is and what it is used for

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.

2.

What you need to know before you receive Ferinject

You must not receive Ferinject

if you are allergic (hypersensitive) to ferric carboxymaltose or any of the other ingredients of this

medicine (listed in section 6).

if you have experienced serious allergic (hypersensitive) reactions to other injectable iron

preparations.

if you have anaemia

not

caused by iron deficiency.

if you have an iron overload (too much iron in your body) or disturbances in the utilisation of iron.

Warnings and Precautions

Talk to your doctor or nurse before receiving Ferinject:

if you have a history of medicine allergy.

if you have systemic lupus erythematosus.

if you have rheumatoid arthritis.

if you have severe asthma, eczema or other allergies.

210611_PIL-YV007/YV080/YV013/MR/E27

if you have an infection.

if you have liver disorders.

if you have or have had low levels of phosphate in the blood.

Ferinject should not be given to children under 14 years.

Incorrect administration of Ferinject may cause leakage of the product at the administration site, which

may lead to irritation of the skin and potentially long lasting brown discolouration at the site of

administration. The administration must be stopped immediately when this occurs.

Other medicines and Ferinject

Tell your doctor if you are using, have recently used or might use any other medicines, including

medicines obtained without prescription. If Ferinject is given together with oral iron preparations, then

these oral preparations could be less efficient.

Pregnancy

There is limited data from the use of Ferinject in pregnant women. It is important to tell your doctor if

you are pregnant, think you may be pregnant, or are planning to have a baby.

If you become pregnant during treatment, you must ask your doctor for advice. Your doctor will

decide whether or not you should be given this medicine.

Breast feeding

If you are breast-feeding, ask your doctor for advice before you are given Ferinject. It is unlikely that

Ferinject represents a risk to the nursing child.

Driving and using machines

Ferinject is unlikely to impair the ability to drive or operate machines.

Important information about some of the ingredients of Ferinject

This medicinal product contains 0.24 mmol (or 5.5 mg) sodium per millilitre of undiluted solution.

This has to be taken into account by patients on a sodium-controlled diet.

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:

By injection, you may receive up to 20 mL of Ferinject, corresponding to 1,000 mg of iron, once a

week directly into the vein.

If you are on dialysis, you may receive Ferinject during a haemodialysis session via the dialyser.

By infusion, you may receive up to 20 mL of Ferinject, corresponding to 1,000 mg of iron, once a

week directly into the vein. Because Ferinject is diluted with sodium chloride solution for the

infusion, it may have a volume of up to 250 mL and appear as a brown solution.

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.

Overdose can cause accumulation of iron in your body. Your doctor will monitor iron parameters to

avoid iron accumulation.

210611_PIL-YV007/YV080/YV013/MR/E27

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects:

Tell your doctor immediately if you experience any of the following signs and symptoms that may

indicate a serious allergic reaction: rash (e.g. hives), itching, difficulty breathing, wheezing and/or

swelling of the lips, tongue, throat or body, and chest pain which can be a sign of a potentially serious

allergic reaction called Kounis syndrome.

In some patients these allergic reactions (affecting less than 1 in 1,000 people) may become severe or

life-threatening (known as anaphylactoid/anaphylactic reactions) and can be associated with heart and

circulation problems and loss of consciousness.

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.

Your doctor is aware of these possible side effects and will monitor you during and after the

administration of Ferinject.

Other side effects that you should tell your doctor about if they become serious:

Common

(may affect up to 1 in 10 people): headache, dizziness, feeling hot (flushing), high blood

pressure, nausea and injection/infusion site reactions (see also section 2).

Uncommon

(may affect up to 1 in 100 people): numbness, tingling or prickling sensation on the skin,

a change in your taste sensation, high heart rate, low blood pressure, difficulty breathing, vomiting,

indigestion, stomach pain, constipation, diarrhoea, itching, hives, redness of the skin, rash, muscle-,

joint -and/or back pain, pain in arms or legs, muscle spasms, fever, tiredness, chest pain, swelling of

the hands and/or the feet, and chills.

Rare

(may affect up to 1 in 1,000 people): inflammation of a vein, a general feeling of discomfort,

anxiety, fainting, feeling faint, wheeze, excessive wind (flatulence), rapid swelling of the face, mouth,

tongue or throat which may cause difficulty in breathing, paleness, and skin discoloration at other

areas of the body than the administration site.

Not known

(frequency cannot be estimated from the available data): loss of consciousness and

swelling of the face.

Flu-like illness (may affect up to 1 in 1,000 people) may occur a few hours to several days after

injection and is typically characterised by symptoms such as high temperature, and aches and pains in

muscles and joints.

Some blood parameters may change temporarily, which could be detected in laboratory tests.

The following change in blood parameters is common: decrease in blood phosphorus.

The following changes in blood parameters are uncommon: increase in certain liver enzymes called

alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase and alkaline

phosphatase, and increase in an enzyme called lactate dehydrogenase.

Ask your doctor for more information.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not

listed in this leaflet. You can also report side effects directly via the national reporting system listed in

210611_PIL-YV007/YV080/YV013/MR/E27

Appendix V*. By reporting side effects you can help provide more information on the safety of this

medicine.

5.

How to store Ferinject

Keep Ferinject out of the sight and reach of children.

Do not use Ferinject after the expiry date which is stated on the label. The expiry date refers to the last

day of that month.

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

Once the Ferinject vials have been opened, they should be used immediately. After dilution with

sodium chloride solution, the diluted solution should be used immediately.

Ferinject will normally be stored for you by your doctor or the hospital.

6.

Contents of the pack and other information

What Ferinject contains

The active substance is iron (as ferric carboxymaltose, an iron carbohydrate compound). The

concentration of iron present in the product is 50 mg per millilitre. The other ingredients are sodium

hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and water for injection.

What Ferinject looks like and contents of the pack

Ferinject is a dark brown, non-transparent solution for injection/infusion.

Ferinject is supplied in glass vials containing:

2 mL solution corresponding to 100 mg iron. Available in pack sizes of 1, 2 and 5 vials.

10 mL solution corresponding to 500 mg iron. Available in pack sizes of 1, 2 and 5 vials.

20 mL solution corresponding to 1,000 mg iron. Available in a pack size of 1 vial.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

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

e-mail: contact-fr@viforpharma.com

This medicine is authorised in the Member States of the European Economic Area and in the

United Kingdom (Northern Ireland) under the following names:

Austria, Bulgaria, Croatia,

Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,

Ireland, Italy, Latvia, Netherlands, Norway, Poland, Portugal, Romania, Slovak Republic, Spain,

Sweden, United Kingdom (Northern Ireland): Ferinject. Belgium, Luxembourg: Injectafer. Slovenia:

Iroprem.

This leaflet was last revised on

11 June 2021.

<For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder.>

210611_PIL-YV007/YV080/YV013/MR/E27

{To be completed nationally}

210611_PIL-YV007/YV080/YV013/MR/E27

The following information is intended for healthcare professionals only:

Monitor patients carefully for signs and symptoms of hypersensitivity reactions during and following

each administration of Ferinject. Ferinject 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 Ferinject administration.

Determination of the iron need

The individual iron need for repletion using Ferinject is determined based on the patient’s body weight

and haemoglobin (Hb) level (see Table 1):

Table 1:

Determination of the iron need

Hb

Patient body weight

g/dL

mmol/L

below 35 kg

35 kg to <70 kg

70 kg and above

<10

<6.2

500 mg

1,500 mg

2,000 mg

10 to <14

6.2 to <8.7

500 mg

1,000 mg

1,500 mg

≥14

≥8.7

500 mg

500 mg

500 mg

Iron deficiency must be confirmed by laboratory tests.

Calculation and administration of the maximum individual iron dose(s)

Based on the iron need determined above the appropriate dose(s) of Ferinject should be administered

taking into consideration the following:

A single Ferinject administration should not exceed:

15 mg iron/kg body weight (intravenous injection) or 20 mg iron/kg body weight (intravenous

infusion)

1,000 mg of iron (20 mL Ferinject)

The maximum recommended cumulative dose of Ferinject is 1,000 mg of iron (20 mL Ferinject) per

week.

A single maximum daily dose of 200 mg iron should not be exceeded in haemodialysis-dependent

chronic kidney disease patients.

The use of Ferinject has not been studied in children, and therefore is not recommended in children

under 14 years.

Method of administration

Ferinject must only be administered by the intravenous route: by injection, by infusion, or

during a haemodialysis session undiluted directly into the venous limb of the dialyser. Ferinject must

not be administered by the subcutaneous or intramuscular route.

Caution should be exercised to avoid paravenous leakage when administering Ferinject. Paravenous

leakage of Ferinject at the administration site may lead to irritation of the skin and potentially long

lasting brown discolouration at the site of administration. In case of paravenous leakage, the

administration of Ferinject must be stopped immediately.

Intravenous injection

Ferinject may be administered by intravenous injection using undiluted solution. The maximum single

dose is 15 mg iron/kg body weight but should not exceed 1,000 mg iron. The administration rates are

as shown in Table 2:

210611_PIL-YV007/YV080/YV013/MR/E27

Table 2:

Administration rates for intravenous injection of Ferinject

Volume of Ferinject

required

Equivalent iron dose

Administration rate /

Minimum administration time

4 mL

200 mg

No minimal prescribed time

>4

10 mL

>200

500 mg

100 mg iron / min

>10

20 mL

>500

1,000 mg

15 minutes

Intravenous infusion

Ferinject may administered by intravenous infusion, in which case it must be diluted. The maximum

single dose is 20 mg iron/kg body weight but should not exceed 1,000 mg iron. Ferinject must only be

diluted in sterile 0.9% m/V sodium chloride solution as shown in Table 3. Note: for stability reasons,

Ferinject should not be diluted to concentrations less than 2 mg iron/mL (not including the volume of

the ferric carboxymaltose solution).

Table 3:

Dilution plan of Ferinject for intravenous infusion

Volume of Ferinject

required

Equivalent iron dose

Maximum amount of

sterile 0.9% m/V

sodium chloride

solution

Minimum

administration

time

4 mL

200 mg

50 mL

No minimal

prescribed time

>4

10 mL

>200

500 mg

100 mL

6 minutes

>10

20 mL

>500

1,000 mg

250 mL

15 minutes

Monitoring measures

Re-assessment should be performed by the clinician based on the individual patient’s condition. The

Hb level should be re-assessed no earlier than 4 weeks post final Ferinject administration to allow

adequate time for erythropoiesis and iron utilisation. In the event the patient requires further iron

repletion, the iron need should be recalculated using Table 1 above

.

Incompatibilities

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 administration of Ferinject.

Overdose

Administration of Ferinject in quantities exceeding the amount needed to correct iron deficit at the

time of administration may lead to accumulation of iron in storage sites eventually leading to

haemosiderosis. Monitoring of iron parameters such as serum ferritin and transferrin saturation may

assist in recognising iron accumulation. If iron accumulation has occurred, treat according to standard

medical practice, e.g. consider the use of an iron chelator.

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1/10

This medicinal product is subject to additional monitoring. This will allow quick identification of

new safety information. Healthcare professionals are asked to report any suspected adverse

reactions. See section 4.8 for how to report adverse reactions.

1.

NAME OF THE MEDICINAL PRODUCT

Ferinject 50 mg iron/mL solution for injection/infusion.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

One mL of solution contains 50 mg of iron as ferric carboxymaltose.

Each 2 mL vial contains 100 mg of iron as ferric carboxymaltose.

Each 10 mL vial contains 500 mg of iron as ferric carboxymaltose.

Each 20 mL vial contains 1,000 mg of iron as ferric carboxymaltose.

Excipient(s) with known effect

One mL of solution contains up to 5.5 mg (0.24 mmol) sodium, see section 4.4.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Solution for injection/infusion. Dark brown, non-transparent, aqueous solution.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Ferinject is indicated for the treatment of iron deficiency when (see section 5.1):

oral iron preparations are ineffective.

oral iron preparations cannot be used.

there is a clinical need to deliver iron rapidly.

The diagnosis of iron deficiency must be based on laboratory tests.

4.2

Posology and method of administration

Monitor carefully patients for signs and symptoms of hypersensitivity reactions during and following

each administration of Ferinject.

Ferinject 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 Ferinject administration (see section 4.4).

Posology

The posology of Ferinject follows a stepwise approach: [1] determination of the individual iron need,

[2] calculation and administration of the iron dose(s), and [3] post-iron repletion assessments. These

steps are outlined below:

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Step 1: Determination of the iron need

The individual iron need for repletion using Ferinject is determined based on the patient’s body weight

and haemoglobin (Hb) level. Refer to Table 1 for determination of the iron need:

Table 1:

Determination of the iron need

Hb

Patient body weight

g/dL

mmol/L

below 35 kg

35 kg to <70 kg

70 kg and above

<10

<6.2

500 mg

1,500 mg

2,000 mg

10 to <14

6.2 to <8.7

500 mg

1,000 mg

1,500 mg

≥14

≥8.7

500 mg

500 mg

500 mg

Iron deficiency must be confirmed by laboratory tests as stated in 4.1.

Step 2: Calculation and administration of the maximum individual iron dose(s)

Based on the iron need determined above the appropriate dose(s) of Ferinject should be administered

taking into consideration the following:

A single Ferinject administration should not exceed:

15 mg iron/kg body weight (for administration by intravenous injection) or 20 mg iron/kg

body weight (for administration by intravenous infusion)

1,000 mg of iron (20 mL Ferinject)

The maximum recommended cumulative dose of Ferinject is 1,000 mg of iron (20 mL Ferinject) per

week.

Step 3: Post-iron repletion assessments

Re-assessment should be performed by the clinician based on the individual patient’s condition. The

Hb level should be re-assessed no earlier than 4 weeks post final Ferinject administration to allow

adequate time for erythropoiesis and iron utilisation. In the event the patient requires further iron

repletion, the iron need should be recalculated using Table 1 above. (See section 5.1.)

Special Population – patients with haemodialysis-dependent chronic kidney disease

A single maximum daily dose of 200 mg iron should not be exceeded in haemodialysis-dependent

chronic kidney disease patients (see also section 4.4).

Paediatric population

The use of Ferinject has not been studied in children, and therefore is not recommended in children

under 14 years.

Method of administration

Ferinject must only be administered by the intravenous route:

by injection, or

by infusion, or

during a haemodialysis session undiluted directly into the venous limb of the dialyser.

Ferinject must not be administered by the subcutaneous or intramuscular route.

Intravenous injection

Ferinject may be administered by intravenous injection using undiluted solution. The maximum single

dose is 15 mg iron/kg body weight but should not exceed 1,000 mg iron. The administration rates are

as shown in Table 2:

3/10

Table 2:

Administration rates for intravenous injection of Ferinject

Volume of Ferinject

required

Equivalent iron dose

Administration rate /

Minimum administration time

4 mL

200 mg

No minimal prescribed time

>4

10 mL

>200

500 mg

100 mg iron / min

>10

20 mL

>500

1,000 mg

15 minutes

Intravenous infusion

Ferinject may be administered by intravenous infusion, in which case it must be diluted. The

maximum single dose is 20 mg iron/kg body weight, but should not exceed 1,000 mg iron.

For infusion, Ferinject must only be diluted in sterile 0.9% m/V sodium chloride solution as shown in

Table 3. Note: for stability reasons, Ferinject should not be diluted to concentrations less than 2 mg

iron/mL (not including the volume of the ferric carboxymaltose solution). For further instructions on

dilution of the medicinal product before administration, see section 6.6.

Table 3:

Dilution plan of Ferinject for intravenous infusion

Volume of Ferinject

required

Equivalent iron dose

Maximum amount of

sterile 0.9% m/V

sodium chloride

solution

Minimum

administration

time

4 mL

200 mg

50 mL

No minimal

prescribed time

>4

10 mL

>200

500 mg

100 mL

6 minutes

>10

20 mL

>500

1,000 mg

250 mL

15 minutes

4.3

Contraindications

The use of Ferinject is contraindicated in cases of:

hypersensitivity to the active substance, to Ferinject or any of its excipients listed in

section 6.1.

known serious hypersensitivity to other parenteral iron products.

anaemia not attributed to iron deficiency, e.g. other microcytic anaemia.

evidence of iron overload or disturbances in the utilisation of iron.

4.4

Special warnings and precautions for use

Hypersensitivity reactions

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. There have been reports of

hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arteriospasm

that can result in myocardial infarction, see section 4.8).

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 administration. If hypersensitivity reactions or signs of intolerance occur during

administration, the treatment must be stopped immediately. Facilities for cardio respiratory

4/10

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.

Hypophosphataemic osteomalacia

Symptomatic hypophosphataemia leading to osteomalacia and fractures requiring clinical intervention

including surgery has been reported in the post marketing setting. Patients should be asked to seek

medical advice if they experience worsening fatigue with myalgias or bone pain.

Serum phosphate should be monitored in patients who receive multiple administrations at higher doses

or long-term treatment, and those with existing risk factors for hypophosphataemia. In case of

persisting hypophosphataemia, treatment with ferric carboxymaltose should be re-evaluated.

Hepatic or renal impairment

In patients with liver dysfunction, parenteral iron should only be administered after careful benefit/risk

assessment. Parenteral iron administration should be avoided in patients with hepatic dysfunction

where iron overload is a precipitating factor, in particular Porphyria Cutanea Tarda (PCT). Careful

monitoring of iron status is recommended to avoid iron overload.

No safety data on haemodialysis-dependent chronic kidney disease patients receiving single doses of

more than 200 mg iron are available.

Infection

Parenteral iron must be used with caution in case of acute or chronic infection, asthma, eczema or

atopic allergies. It is recommended that the treatment with Ferinject is stopped in patients with

ongoing bacteraemia. Therefore, in patients with chronic infection a benefit/risk evaluation has to be

performed, taking into account the suppression of erythropoiesis.

Extravasation

Caution should be exercised to avoid paravenous leakage when administering Ferinject. Paravenous

leakage of Ferinject at the administration site may lead to irritation of the skin and potentially long

lasting brown discolouration at the site of administration. In case of paravenous leakage, the

administration of Ferinject must be stopped immediately.

Excipients

One mL of undiluted Ferinject contains up to 5.5 mg (0.24 mmol) of sodium. This has to be taken into

account in patients on a sodium-controlled diet.

Paediatric population

The use of Ferinject has not been studied in children.

4.5

Interaction with other medicinal products and other forms of interaction

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 administration of Ferinject.

4.6

Fertility, pregnancy and lactation

Pregnancy

There are limited data from the use of Ferinject in pregnant women (see section 5.1). A careful

benefit/risk evaluation is required before use during pregnancy and Ferinject should not be used during

pregnancy unless clearly necessary.

Iron deficiency occurring in the first trimester of pregnancy can in many cases be treated with oral

iron. Treatment with Ferinject should be confined to the second and third trimester if the benefit is

judged to outweigh the potential risk for both the mother and the foetus.

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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.

Animal data suggest that iron released from Ferinject can cross the placental barrier and that its use

during pregnancy may influence skeletal development in the fetus (see section 5.3).

Breast-feeding

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.

Fertility

There are no data on the effect of Ferinject on human fertility. Fertility was unaffected following

Ferinject treatment in animal studies (see section 5.3).

4.7

Effects on ability to drive and use machines

Ferinject is unlikely to impair the ability to drive and use machines.

4.8

Undesirable effects

Table 4 presents the adverse drug reactions (ADRs) reported during clinical studies in which >8,000

subjects received Ferinject, as well as those reported from the post-marketing experience (see table

footnotes for details).

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. The most serious ADR is anaphylactoid/anaphylactic reactions (rare); fatalities have been

reported. See section 4.4 for further details.

Table 4:

Adverse drug reactions observed during clinical trials and post-marketing

experience

System Organ Class

Common (≥1/100

to <1/10)

Uncommon

(≥1/1,000 to

<1/100)

Rare

(≥1/10,000 to

<1/1,000)

Frequency not

known

(1)

Immune system

disorders

Hypersensitivity

Anaphylactoid/

anaphylactic

reactions

Metabolism and

nutritional disorders

Hypophosphataemia

Nervous system

disorders

Headache, dizziness

Paraesthesia,

dysgeusia

Loss of

consciousness

Psychiatric

disorders

Anxiety

Cardiac disorders

Tachycardia

Kounis syndrome

Vascular disorders

Flushing,

hypertension

Hypotension

Phlebitis,

syncope

presyncope

Respiratory,

thoracic and

mediastinal

disorders

Dyspnoea

Bronchospasm

Gastrointestinal

disorders

Nausea

Vomiting,

dyspepsia,

abdominal pain,

Flatulence

6/10

System Organ Class

Common (≥1/100

to <1/10)

Uncommon

(≥1/1,000 to

<1/100)

Rare

(≥1/10,000 to

<1/1,000)

Frequency not

known

(1)

constipation,

diarrhoea

Skin and

subcutaneous tissue

disorders

Pruritus, urticaria,

erythema, rash

Angioedema

pallor

distant skin

discolouration

Face oedema

Musculoskeletal and

connective tissue

disorders

Myalgia, back pain,

arthralgia,

pain

extremity,

muscle

spasms

Hypophosphataemic

osteomalacia

General disorders

and administration

site conditions

Injection/infusion

site

reactions

Pyrexia, fatigue,

chest pain, oedema

peripheral, chills

Malaise,

influenza like

illness (whose

onset may vary

from a few

hours to several

days)

Investigations

Alanine

aminotransferase

increased, aspartate

aminotransferase

increased, gamma-

glutamyltransferase

increased, blood

lactate

dehydrogenase

increased, blood

alkaline

phosphatase

increased

1 ADRs exclusively reported in the post-marketing setting; estimated as rare.

2 ADRs reported in the post-marketing setting which are also observed in the clinical setting.

Includes the following preferred terms: rash (individual ADR determined to be uncommon) and rash erythematous, -generalised, -macular,

-maculo-papular, -pruritic (all individual ADRs determined to be rare).

4 Includes, but is not limited to, the following preferred terms: injection/infusion site -pain, -haematoma, -discolouration, -extravasation, -

irritation, -reaction, (all individual ADRs determined to be uncommon) and -paraesthesia (individual ADR determined to be rare).

Note: ADR = Adverse drug reaction.

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*.

4.9

Overdose

Administration of Ferinject in quantities exceeding the amount needed to correct iron deficit at the

time of administration may lead to accumulation of iron in storage sites eventually leading to

haemosiderosis. Monitoring of iron parameters such as serum ferritin and transferrin saturation may

assist in recognising iron accumulation. If iron accumulation has occurred, treat according to standard

medical practice, e.g. consider the use of an iron chelator.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

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

7/10

Ferinject solution for injection/infusion is a colloidal solution of the iron complex ferric

carboxymaltose.

The complex is designed to provide, in a controlled way, utilisable iron for the iron transport and

storage proteins in the body (transferrin and ferritin, respectively).

Red cell utilisation of

Fe from radio-labelled Ferinject ranged from 91% to 99% in subjects with iron

deficiency (ID) and 61% to 84% in subjects with renal anaemia at 24 days post-dose.

Ferinject treatment results in an increase in reticulocyte count, serum ferritin levels and TSAT levels

to within normal ranges.

Clinical efficacy and safety

The efficacy and safety of Ferinject has been studied in different therapeutic areas necessitating

intravenous iron to correct iron deficiency. The main studies are described in more detail below.

Cardiology

Chronic heart failure

Study CONFIRM-HF was a double-blind, randomised, 2-arm study comparing Ferinject (n=150) vs.

placebo (n=151) in subjects with chronic heart failure and ID for a treatment period of 52 weeks. At

Day 1 and Week 6 (correction phase), subjects received either Ferinject according to a simplified

dosing grid using baseline Hb and body weight at screening (see section 4.2), placebo or no dose. At

Weeks 12, 24, and 36 (maintenance phase) subjects received Ferinject (500 mg iron) or placebo if

serum ferritin was <100 ng/mL or 100-300 ng/mL with TSAT <20%. The treatment benefit of

Ferinject vs. placebo was demonstrated with the primary efficacy endpoint, the change in the 6-minute

walk test (6MWT) from baseline to Week 24 (33±11 metres, p=0.002). This effect was sustained

throughout the study to Week 52 (36±11 metres, p<0.001).

Study EFFECT-HF was an open-label (with blinded endpoint evaluation), randomised, 2-arm study

comparing Ferinject (n=86) vs. standard of care (n=86) in subjects with chronic heart failure and ID

for a treatment period of 24 weeks. At Day 1 and Week 6 (correction phase), subjects received either

Ferinject according to a simplified dosing grid using baseline Hb and body weight at screening (see

section 4.2) or standard of care. At Week 12, (maintenance phase) subjects received Ferinject (500 mg

iron) or standard of care if serum ferritin <100 ng/ml or 100 to 300 ng/ml and TSAT <20%. The

treatment benefit of Ferinject vs. standard of care was demonstrated with the primary efficacy

endpoint, the change in weight-adjusted peak VO

from baseline to Week 24 (LS Mean 1.04 ±0.44 ,

p=0.02).

Nephrology

Haemodialysis-dependent chronic kidney disease

Study VIT-IV-CL-015 was an open-label, randomised parallel group study comparing Ferinject

(n=97) to iron sucrose (n=86) in subjects with ID anaemia undergoing haemodialysis. Subjects

received Ferinject or iron sucrose 2-3 times per week in single doses of 200 mg iron directly into the

dialyser until the individually calculated cumulative iron dose was reached (mean cumulative dose of

iron as Ferinject: 1,700 mg). The primary efficacy endpoint was the percentage of subjects reaching an

increase in Hb of ≥1.0 g/dL at 4 weeks after baseline. At 4 weeks after baseline, 44.1% responded to

treatment with Ferinject (i.e. Hb increase of ≥1.0 g/dL) compared to 35.3% for iron sucrose

(p=0.2254).

Non

dialysis-dependent chronic kidney disease

Study 1VIT04004 was an open-label, randomised active-control study, evaluating the safety and

efficacy of Ferinject (n=147) vs. oral iron (n=103). Subjects in the Ferinject group received 1,000 mg

of iron at baseline and 500 mg of iron at days 14 and 28, if TSAT was <30% and serum ferritin was

<500 ng/mL at the respective visit. Subjects in the oral iron arm received 65 mg iron TID as ferrous

sulphate from baseline to day 56. Subjects were followed-up until day 56. The primary efficacy

endpoint was the percentage of subjects achieving an increase in Hb of ≥1.0 g/dL anytime between

8/10

baseline and end of study or time of intervention. This was achieved by 60.54% of subjects receiving

Ferinject vs. 34.7% of subjects in the oral iron group (p<0.001). Mean haemoglobin change to day

56/end of study was 1.0 g/dL in the Ferinject group and 0.7 g/dL in the oral iron group (p=0.034, 95%

CI: 0.0, 0.7).

Gastroenterology

Inflammatory bowel disease

Study VIT-IV-CL-008 was a randomised, open-label study which compared the efficacy of Ferinject

vs. oral ferrous sulphate in reducing ID anaemia in subjects with inflammatory bowel disease (IBD).

Subjects received either Ferinject (n=111) in single doses of up to 1,000 mg iron once per week until

the individually calculated iron dose (per Ganzoni formula) was reached (mean cumulative iron dose:

1,490 mg), or 100 mg iron BID as ferrous sulphate (n=49) for 12 weeks. Subjects receiving Ferinject

showed a mean increase in Hb from baseline to Week 12 of 3.83 g/dL, which was non-inferior to

12 weeks of twice daily therapy with ferrous sulphate (3.75 g/dL, p=0.8016).

Study FER-IBD-07-COR was a randomised, open-label study comparing the efficacy of Ferinject vs.

iron sucrose in subjects with remitting or mild IBD. Subjects receiving Ferinject were dosed according

to a simplified dosing grid using baseline Hb and body weight (see section 4.2) in single doses up to

1,000 mg iron, whereas subjects receiving iron sucrose were dosed according to individually

calculated iron doses using the Ganzoni formula in doses of 200 mg iron until the cumulative iron

dose was reached. Subjects were followed-up for 12 weeks. 65.8% of subjects receiving Ferinject

(n=240; mean cumulative iron dose: 1,414 mg) vs. 53.6% receiving iron sucrose (n=235; mean

cumulative dose 1,207 mg; p=0.004) had responded at Week 12 (defined as Hb increase ≥2 g/dL).

83.8% of Ferinject-treated subjects vs. 75.9% of iron sucrose-treated subjects achieved a Hb increase

≥2 g/dL or had Hb within normal limits at Week 12 (p=0.019).

Women’s health

Post partum

Study VIT-IV-CL-009 was a randomised open-label non-inferiority study comparing the efficacy of

Ferinject (n=227) vs. ferrous sulphate (n=117) in women suffering from post-partum anaemia.

Subjects received either Ferinject in single doses of up to 1,000 mg iron until their individually

calculated cumulative iron dose (per Ganzoni formula) was reached, or 100 mg of iron as oral ferrous

sulphate BID for 12 weeks. Subjects were followed-up for 12 weeks. The mean change in Hb from

baseline to Week 12 was 3.37 g/dL in the Ferinject group (n=179; mean cumulative iron dose:

1,347 mg) vs. 3.29 g/dL in the ferrous sulphate group (n=89), showing non-inferiority between the

treatments.

Pregnancy

Intravenous iron medicines should not be used during pregnancy unless clearly necessary. Treatment

with Ferinject should be confined to the second and third trimester if the benefit is judged to outweigh

the potential risk for both the mother and the foetus, see section 4.6.

Limited safety data in pregnant women are available from study FER-ASAP-2009-01, a randomised,

open-label, study comparing Ferinject (n=121) vs. oral ferrous sulphate (n=115) in pregnant women in

the second and third trimester with ID anaemia for a treatment period of 12 weeks. Subjects received

Ferinject in cumulative doses of 1,000 mg or 1,500 mg of iron (mean cumulative dose: 1,029 mg iron)

based on Hb and body weight at screening, or 100 mg of oral iron BID for 12 weeks. The incidence of

treatment related adverse events was similar between Ferinject treated women and those treated with

oral iron (11.4% Ferinject group; 15.3% oral iron group). The most commonly reported treatment-

related adverse events were nausea, upper abdominal pain and headache. Newborn Apgar scores as

well as newborn iron parameters were similar between treatment groups.

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,

9/10

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.

5.2

Pharmacokinetic properties

Distribution

Positron emission tomography demonstrated that

Fe and

Fe from Ferinject was rapidly eliminated

from the blood, transferred to the bone marrow, and deposited in the liver and spleen.

After administration of a single dose of Ferinject of 100 to 1,000 mg of iron in ID subjects, maximum

total serum iron levels of 37 µg/mL up to 333 µg/mL are obtained after 15 minutes to 1.21 hours

respectively. The volume of the central compartment corresponds well to the volume of the plasma

(approximately 3 litres).

Elimination

The iron injected or infused was rapidly cleared from the plasma, the terminal half-life ranged from

7 to 12 hours, the mean residence time (MRT) from 11 to 18 hours. Renal elimination of iron was

negligible.

5.3

Preclinical safety data

Preclinical data revealed no special hazard for humans based on conventional studies of safety

pharmacology, repeat dose toxicity and genotoxicity. Preclinical studies indicate that iron released

from Ferinject does cross the placental barrier and is excreted in milk in limited, controlled amounts.

In reproductive toxicology studies using iron replete rabbits Ferinject was associated with minor

skeletal abnormalities in the fetus. In a fertility study in rats, there were no effects on fertility for either

male or female animals. No long-term studies in animals have been performed to evaluate the

carcinogenic potential of Ferinject. No evidence of allergic or immunotoxic potential has been

observed. A controlled in-vivo test demonstrated no cross-reactivity of Ferinject with anti-dextran

antibodies. No local irritation or intolerance was observed after intravenous administration.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Sodium hydroxide (for pH adjustment)

Hydrochloric acid (for pH adjustment)

Water for injections

6.2

Incompatibilities

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

section 6.6.

The compatibility with containers other than polyethylene and glass is not known.

6.3

Shelf life

Shelf life of the product as packaged for sale:

3 years.

Shelf life after first opening of the container:

From a microbiological point of view, preparations for parenteral administration should be used

immediately.

Shelf life after dilution with sterile 0.9% m/V sodium chloride solution:

10/10

From a microbiological point of view, preparations for parenteral administration should be used

immediately after dilution with sterile 0.9% m/V sodium chloride solution.

6.4

Special precautions for storage

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

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

6.5

Nature and contents of container

Ferinject is supplied in a vial (type I glass) with a stopper (bromobutyl rubber) and an aluminium cap

- 2 mL solution containing 100 mg iron. Available in pack sizes of 1, 2 and 5 vials.

- 10 mL solution containing 500 mg iron. Available in pack sizes of 1, 2 and 5 vials.

- 20 mL solution containing 1,000 mg iron. Available in a pack size of 1 vial.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling

Inspect vials visually for sediment and damage before use. Use only those containing sediment-free,

homogeneous solution.

Each vial of Ferinject is intended for single use only. Any unused product or waste material should be

disposed of in accordance with local requirements.

Ferinject must only be mixed with sterile 0.9% m/V sodium chloride solution. No other intravenous

dilution solutions and therapeutic agents should be used, as there is the potential for precipitation

and/or interaction. For dilution instructions, see section 4.2.

7.

MARKETING AUTHORISATION HOLDER

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

8.

MARKETING AUTHORISATION NUMBER

<[To be completed nationally]>

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

<Date of first authorisation: {DD month YYYY}>

<Date of latest renewal: {DD month YYYY}>

10.

DATE OF REVISION OF THE TEXT

11 June 2021.

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