- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
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.
PosologyThe posology of Ferinject follows a stepwise approach:  determination of the individual iron need,  calculation and administration of the iron dose(s), and  post-iron repletion assessments. These steps are outlined below:
Step 1: Determination of the iron needThe 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 over|
|<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|
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 assessmentsRe-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 diseaseA single maximum daily injection dose of 200 mg iron should not be exceeded in haemodialysis-dependent chronic kidney disease patients (see also section 4.4).
Paediatric populationThe use of Ferinject has not been studied in children, and therefore is not recommended in children under 14 years.
Method of administrationFerinject 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 injectionFerinject 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: Table 2: Administration rates for intravenous injection of Ferinject
|Volume of Ferinject required||Equivalent iron dose||Administration rate / Minimum administration time|
|2||To||4 mL||100||to||200 mg||No minimal prescribed time|
|>4||To||10 mL||>200||to||500 mg||100 mg iron / min|
|>10||To||20 mL||>500||to||1,000 mg||15 minutes|
Intravenous infusionFerinject 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). 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|
|2||to||4 mL||100||to||200 mg||50 mL||-|
|>4||to||10 mL||>200||to||500 mg||100 mL||6 minutes|
|>10||to||20 mL||>500||to||1,000 mg||250 mL||15 minutes|
Hypersensitivity reactionsParenterally 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.
Hepatic or renal impairmentIn 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.
InfectionParenteral 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.
ExtravasationCaution should be exercised to avoid paravenous leakage when administering Ferinject. Paravenous leakage of Ferinject at the injection site may lead to irritation of the skin and potentially long lasting brown discolouration at the site of injection. In case of paravenous leakage, the administration of Ferinject must be stopped immediately.ExcipientsOne 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 populationThe use of Ferinject has not been studied in children.
PregnancyThere are no adequate and well-controlled trials of Ferinject in pregnant women. 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.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-feedingClinical 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.
FertilityThere are no data on the effect of Ferinject on human fertility. Fertility was unaffected following Ferinject treatment in animal studies (see section 5.3).
|System Organ Class||Common (≥1/100 to <1/10)||Uncommon (≥1/1000 to <1/100)||Rare (≥1/10000 to <1/1000)|
|Immune system disorders||Hypersensitivity||Anaphylactoid reactions|
|Nervous system disorders||Headache, dizziness||Paraesthesia, dysgeusia||Loss of consciousness(3)|
|Vascular disorders||Hypertension||Hypotension, flushing||Phlebitis, syncope(4), presyncope(4)|
|Respiratory, thoracic and mediastinal disorders||Dyspnoea||Bronchospasm(4)|
|Gastrointestinal disorders||Nausea||Vomiting, dyspepsia, abdominal pain, constipation, diarrhoea||Flatulence|
|Skin and subcutaneous tissue disorders||Pruritus, urticaria, erythema, rash(1)||Angioedema(4), pallor(3), and face oedema(3)|
|Musculoskeletal and connective tissue disorders||Myalgia, back pain, arthralgia, muscle spasms|
|General disorders and administration site conditions||Injection site reactions(2)||Pyrexia, fatigue, chest pain, oedema peripheral, chills||Rigors, malaise, influenza like illness(4)|
|Investigations||Alanine aminotransferase increased||Aspartate aminotransferase increased, gamma-glutamyltransferase increased, blood lactate dehydrogenase increased, blood alkaline phosphatase increased|
|Metabolism and nutritional disorders||Hypophosphataemia|
Reporting of suspected adverse reactionsReporting 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:
United KingdomYellow Card SchemeWebsite: www.mhra.gov.uk/yellowcard
MaltaADR ReportingThe Medicines Authority Post-Licensing Directorate203 Level 3, Rue D'ArgensGŻR-1368 GżiraWebsite: www.medicinesauthority.gov.mte-mail: email@example.com
Clinical efficacy and safetyThe 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.
Haemodialysis-dependent chronic kidney diseaseStudy 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 patients 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 diseaseStudy 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 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).
Inflammatory bowel diseaseStudy VIT-CL-IV-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. Patients were followed-up for 12 weeks. 65.8% of patients 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 patients vs. 75.9% of iron sucrose-treated patients achieved a Hb increase ≥2 g/dL or had Hb within normal limits at Week 12 (p=0.019).
Post partumStudy 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. Patients 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.
Ferritin monitoring after replacement therapyThere 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.
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: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.
|Date of first authorisation:||United Kingdom: 19.07.2007 Malta: 09.04.2010|
Vifor Pharma UK Limited
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+44 (0)1276 853 633
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