- 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.
Determination of the cumulative iron doseThe cumulative dose for repletion of iron using Ferinject is determined based on the patient's body weight and haemoglobin (Hb) level and must not be exceeded. The following table (Table 1) should be used to determine the cumulative iron dose:Table 1: Determination of the cumulative iron dose
|Hb (g/dL)||Patients with body weight 35 kg to <70 kg||Patients with body weight≥70 kg|
|<10||1,500 mg||2,000 mg|
|≥10||1,000 mg||1,500 mg|
Maximum tolerated single doseA single dose of Ferinject should not exceed 1,000 mg of iron (20 mL) per day. Do not administer 1,000 mg of iron (20 mL) more than once a week.
Intravenous injectionFerinject may be administered by intravenous injection using undiluted solution up to 1,000 mg iron (up to a maximum of 15 mg/kg body weight). For doses up to 200 mg iron, there is no prescribed administration time. For doses greater than 200 and up to 500 mg iron, Ferinject should be administered at a rate of 100 mg/min. For doses greater than 500 and up to 1,000 mg iron, Ferinject should be administered over 15 minutes.
Intravenous infusionFerinject may be administered by intravenous infusion up to a maximum single dose of 1,000 mg of iron (up to a maximum of 20 mg/kg body weight).
Method of administrationFerinject must be administered only by the intravenous route: by bolus injection, or during a haemodialysis session undiluted directly into the venous limb of the dialyser, or by infusion. In case of infusion Ferinject must be diluted only in sterile 0.9% m/V sodium chloride solution as shown in Table 2 below.Table 2: Dilution plan of Ferinject for intravenous infusion
|Ferinject||Iron||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|
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.
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 nursing women it is unlikely that Ferinject represents a risk to the nursing 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, diahorrea||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|
|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.
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|
Vifor Pharma UK Limited
The Old Stables, Bagshot Park, Surrey, GU19 5PJ, UK
+44 (0)1276 452 341
+44 (0)1276 853 600
+44 (0)1276 853 633
+44 (0)1276 452 341