Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: 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
The use of Ferinject is contraindicated in cases of:
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 administration. 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.
Parenterally administered iron preparations can cause hypophosphataemia which in most cases is transient and without clinical symptoms. Cases of hypophosphataemia requiring medical attention were reported, mainly in patients with existing risk factors and after prolonged exposure to high-dose intravenous iron.
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.
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.
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.
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.
The use of Ferinject has not been studied in children.
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.
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.
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).
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.
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).
Ferinject is unlikely to impair the ability to drive and use machines.
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 known1 |
|---|---|---|---|---|
| Immune system disorders | Hypersensitivity | Anaphylactoid/anaphylactic reactions | ||
| Metabolism and nutritional disorders | Hypophosphataemia | |||
| Nervous system disorders | Headache, dizziness | Paraesthesia, dysgeusia | Loss of consciousness1 | |
| Psychiatric disorders | Anxiety2 | |||
| Cardiac disorders | Tachycardia | Kounis syndrome1 | ||
| Vascular disorders | Flushing, hypertension | Hypotension | Phlebitis, syncope2, presyncope2 | |
| Respiratory, thoracic and mediastinal disorders | Dyspnoea | Bronchospasm2 | ||
| Gastrointestinal disorders | Nausea | Vomiting, dyspepsia, abdominal pain, constipation, diarrhoea | Flatulence | |
| Skin and subcutaneous tissue disorders | Pruritus, urticaria, erythema, rash3 | Angioedema2, pallor2, distant skin discolouration2 | Face oedema1 | |
| Musculoskeletal and connective tissue disorders | Myalgia, back pain, arthralgia, pain in extremity, muscle spasms | Hypophosphataemic osteomalacia1 | ||
| General disorders and administration site conditions | Injection/infusion site reactions4 | Pyrexia, fatigue, chest pain, oedema peripheral, chills | Malaise, influenza like illness (whose onset may vary from a few hours to several days)2 | |
| 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.
3 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 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: Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
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.
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