VENOFER Solution for injection Ref.[9414] Active ingredients: Iron sucrose

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 including iron sucrose. 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). In several studies performed in patients who had a history of a hypersensitivity reaction to iron dextran or ferric gluconate, Venofer was shown to be well tolerated. For known serious hypersensitivity to other parenteral iron product see section 4.3.

The risk of hypersensitivity reactions 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).

Venofer 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. Each patient should be observed for adverse effects for at least 30 minutes following each Venofer 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 patients with liver dysfunction, parenteral iron should only be administered after careful risk/benefit 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.

Parenteral iron should be used with caution in the case of acute or chronic infection. It is recommended that the administration of Venofer is stopped in patients with bacteraemia. In patients with chronic infection, a risk/benefit evaluation should be performed.

Paravenous leakage must be avoided because leakage of Venofer at the injection site can lead to pain, inflammation and brown discoloration of the skin.

As with all parenteral iron preparations, Venofer should not be administered concomitantly with oral iron preparations since the absorption of oral iron is reduced. Therefore, oral iron therapy should be started at least 5 days after the last injection of Venofer.

Pregnancy

There is no data from the use of iron sucrose in pregnant women in the first trimester. Data (303 pregnancy outcomes) from the use of Venofer in pregnant women in the second and third trimester showed no safety concerns for the mother or newborn.

A careful risk/benefit evaluation is required before use during pregnancy and Venofer should not be used during pregnancy unless clearly necessary (see section 4.4).

Iron deficiency anaemia occurring in the first trimester of pregnancy can in many cases be treated with oral iron. Treatment with Venofer should be confined to 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 studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Breast-feeding

There is limited information on the excretion of iron in human milk following administration of intravenous iron sucrose. In one clinical study, 10 healthy breast-feeding mothers with iron deficiency received 100 mg iron in the form of iron sucrose. Four days after treatment, the iron content of the breast milk had not increased and there was no difference from the control group (n=5). It cannot be excluded that newborns/infants may be exposed to iron derived from Venofer via the mother’s milk, therefore the risk/benefit should be assessed.

Preclinical data do not indicate direct or indirect harmful effects to the nursing child. In lactating rats treated with ⁵⁹Fe-labelled iron sucrose, low secretion of iron into the milk and transfer of iron into the offspring was observed. Non metabolised iron sucrose is unlikely to pass into the mother’s milk.

Fertility

No effects of iron sucrose treatment were observed on fertility and mating performance in rats.

In the case of symptoms of dizziness, confusion or light headedness following the administration of Venofer, patients should not drive or use machinery until the symptoms have ceased.

The most commonly reported adverse drug reaction in clinical trials with Venofer was dysgeusia, which occurred with a rate of 4.5 events per 100 subjects. The most important serious adverse drug reactions associated with Venofer are hypersensitivity reactions, which occurred with a rate of 0.25 events per 100 subjects in clinical trials. Anaphylactoid/anaphylactic reactions were reported only in the post-marketing setting (estimated as rare); fatalities have been reported. See section 4.4.

The adverse drug reactions reported after the administration of Venofer in 4,064 subjects in clinical trials as well as those reported from the post-marketing setting are presented in the table below.

Common (≥1/100, <1/10)
Uncommon (≥1/1,000, <1/100)
Rare (≥1/10,000, <1/1,000)
Frequency not known¹

Immune system disorders

Uncommon: Hypersensitivity

Frequency not known¹: Anaphylactoid/anaphylactic reactions, angioedema

Nervous system disorders

Common: Dysgeusia

Uncommon: Headache, dizziness, paraesthesia, hypoaesthesia

Rare: Syncope, somnolence

Frequency not known¹: Depressed level of consciousness, confusional state, loss of consciousness, anxiety, tremor

Cardiac disorders

Rare: Palpitations

Frequency not known¹: Bradycardia, tachycardia, Kounis syndrome

Vascular disorders

Common: Hypotension, hypertension

Uncommon: Flushing, phlebitis

Frequency not known¹: Circulatory collapse, thrombophlebitis

Respiratory, thoracic and mediastinal disorders

Uncommon: Dyspnoea

Frequency not known¹: Bronchospasm

Renal and urinary disorders

Rare: Chromaturia

Gastrointestinal disorders

Common: Nausea

Uncommon: Vomiting, abdominal pain, diarrhoea, constipation

Skin and subcutaneous tissue disorders

Uncommon: Pruritus, rash

Frequency not known¹: Urticaria, erythema

Musculoskeletal and connective tissue disorders

Uncommon: Muscle spasm, myalgia, arthralgia, pain in extremity, back pain

General disorders and administration site conditions

Common: Injection/infusion site reaction²

Uncommon: Chills, asthenia, fatigue, oedema peripheral, pain

Rare: Chest pain, hyperdrosis, pyrexia

Frequency not known¹: Cold sweat, malaise, pallor, influenza like illness³

Investigations

Uncommon: Alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased, serum ferritin increased

Rare: Blood lactate dehydrogenase increased

¹ Spontaneous reports from the post-marketing setting; estimated as rare
² The most frequently reported are: injection/infusion site pain, -extravasation, -irritation, -reaction, -discolouration, -haematoma, -pruritus.
³ Onset may vary from a few hours to several days.

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 Yellow Card Scheme at: 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. There is the potential for precipitation and/or interaction if mixed with other solutions or medicinal products. The compatibility with containers other than glass, polyethylene and PVC is not known.