MONOFER Solution for injection / infusion Ref.[8278] Active ingredients: Iron (III) isomaltoside

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).

Monofer 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 Monofer 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 compensated liver dysfunction, parenteral iron should only be administered after careful benefit/risk assessment. Parenteral iron administration should be avoided in patients with hepatic dysfunction (alanine aminotransferase and/or aspartate aminotransferase >3 times upper limit of normal) 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 case of acute or chronic infection.

Monofer should not be used in patients with ongoing bacteraemia.

Hypotensive episodes may occur if intravenous injection is administered too rapidly.

Caution should be exercised to avoid paravenous leakage when administrating Monofer. Paravenous leakage of Monofer 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 Monofer must be stopped immediately.

As with all parenteral iron preparations the absorption of oral iron is reduced when administered concomitantly. Oral iron therapy should not be started earlier than 5 days after the last injection of Monofer.

Large doses of parenteral iron (5 ml or more) have been reported to give a brown colour to serum from a blood sample drawn four hours after administration.

Parenteral iron may cause falsely elevated values of serum bilirubin and falsely decreased values of serum calcium.

Pregnancy

There are no adequate and well-controlled trials of Monofer in pregnant women. A careful risk/benefit evaluation is therefore required before use during pregnancy and Monofer should not be used during pregnancy unless clearly necessary.

Iron deficiency anaemia occurring in the first trimester of pregnancy can in many cases be treated with oral iron. Treatment with Monofer 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. In rare cases, foetal bradycardia has been observed in pregnant women with hypersensitivity reactions (see section 4.8).

Breast-feeding

A clinical study showed that transfer of iron from Monofer to human milk was very low. At therapeutic doses of Monofer no effects on the breastfeed newborns/infants are anticipated.

Fertility

There are no data on the effect of Monofer on human fertility. Fertility was unaffected following Monofer treatment in animal studies (see section 5.3).

No studies on the effects on the ability to drive and use machines have been performed.

The table presents the adverse drug reactions (ADRs) reported during Monofer treatment in clinical trials and in-market experience.

Acute severe hypersensitivity reactions may occur with parenteral iron preparations. They usually occur within the first few minutes of administration and are generally characterised by the sudden onset of respiratory difficulty and/or cardiovascular collapse; fatalities have been reported. Other less severe manifestations of immediate hypersensitivity, such as urticaria and itching may also occur. In pregnancy, associated foetal bradycardia may occur with parenteral iron preparations.

Flushing in the face, acute chest and/or back pain and tightness sometimes with dyspnea in association with IV iron treatment may occur (frequency uncommon). This may mimic the early symptoms of an anaphylactoid/anaphylactic reaction. The infusion should be stopped and the patient’s vital signs should be assessed. These symptoms disappear shortly after the iron administration is stopped. They typically do not reoccur if the administration is restarted at a lower infusion rate.

Adverse drug reactions observed during clinical trials and post-marketing experience:

Common (≥1/100 to <1/10)
Uncommon (≥1/1000 to <1/100)
Rare (≥1/10000 to <1/1000)

Immune system disorders

Uncommon: Hypersensitivity, including severe reactions

Rare: Anaphylactoid/anaphylactic reactions

Nervous system disorders

Uncommon: Headache, paraesthesia, dysgeusia, blurred vision, loss of consciousness, dizziness, fatigue

Rare: Dysphonia, seizure, tremor, altered mental status

Cardiac disorders

Uncommon: Tachycardia

Rare: Arrhythmia

Vascular disorders

Uncommon: Hypotension, hypertension

Respiratory, thoracic and mediastinal disorders

Uncommon: Chest pain, dyspnoea, bronchospasm

Gastrointestinal disorders

Common: Nausea

Uncommon: Abdominal pain, vomiting, dyspepsia, constipation, diarrhoea

Skin and subcutaneous tissue disorders

Uncommon: Pruritus, urticaria, rash, flushing, sweating, dermatitis

Rare: Angioedema

Metabolism and nutritional disorders

Uncommon: Hypophosphataemia

Musculoskeletal and connective tissue disorders

Uncommon: Back pain, myalgia, arthralgia, muscle spasms

General disorders and administration site conditions

Common: Injection site reactions*

Uncommon: Pyrexia, chills/shivering, infection, local phlebitic reaction

Rare: Malaise, influenza like illness**

Investigations

Uncommon: Hepatic enzyme increased

* Includes the following preferred terms, i.e. injection site erythema, -swelling, -burning, -pain, -bruising, -discolouration, -extravasation, -irritation, -reaction.
** Influenza like illness whose onset may vary from a few hours to several days.

Description of selected adverse reactions

Delayed reactions may also occur with parenteral iron preparations and can be severe. They are characterised by arthralgia, myalgia and sometimes fever. The onset varies from several hours up to four days after administration. Symptoms usually last two to four days and settle spontaneously or following the use of simple analgesics.

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, Website: www.mhra.gov.uk/yellowcard.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.