DIAFER Solution for injection Ref.[27657] Active ingredients:

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. 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).

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).

Diafer 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 Diafer 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.

Parenteral iron should be used with caution in case of acute or chronic infection.

Diafer 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 Diafer. Paravenous leakage of Diafer 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 Diafer must be stopped immediately.

One ml of undiluted Diafer contains up to 4.6 mg (0.2 mmol) of sodium. This has to be taken into account in patients on a sodium-controlled diet.

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 Diafer.

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 Diafer in pregnant women. A careful risk/benefit evaluation is therefore required before use during pregnancy and Diafer 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 Diafer 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.

Breastfeeding

There is no information available on the excretion of Diafer in the human breast milk.

Fertility

There is no information available on the possible effects of Diafer on male and female fertility.

Diafer has no or negligible influence on the ability to drive and use machines.

Due to limited clinical data on Diafer the mentioned undesirable effects are primarily based on safety data for other parenteral iron solutions.

More than 1% of patients may be expected to experience adverse reactions.

Acute, severe anaphylactoid reactions may occur with parenteral iron preparations, although they are uncommon. 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 are also uncommon and include urticaria, rashes, itching, nausea and shivering. Administration must be stopped immediately if signs of an anaphylactoid reaction are observed.

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. In addition, exacerbation of joint pain in rheumatoid arthritis can occur and local reactions may cause pain and inflammation at or near injection site and a local phlebitic reaction.

Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very Rare (<1/10,000)
Not known (cannot be estimated with the available data)

Cardiac disorders

Rare: Arrhythmia, tachycardia

Very rare: Foetal bradycardia, palpitations

Not known: Kounis syndrome

Blood and lymphatic system disorders

Very rare: Haemolysis

Nervous system disorders

Uncommon: Blurred vision, numbness, dysphonia

Rare: Loss of consciousness, seizure, dizziness, restlessness, tremor, fatigue, altered mental status

Very rare: Headache, paresthesia

Ear and labyrinth disorders

Very rare: Transient deafness

Respiratory, thoracic and mediastinal disorders

Uncommon: Dyspnoea

Rare: Chest pain

Gastrointestinal disorders

Uncommon: Nausea, emesis, abdominal pain, constipation

Rare: Diarrhoea

Skin and subcutaneous tissue disorders

Uncommon: Flushing, pruritus, rash

Rare: Angioedema, sweating

Musculoskeletal and connective tissue disorders

Uncommon: Cramps

Rare: Myalgias, arthralgia

Vascular disorders

Rare: Hypotension

General disorders and administration site conditions

Uncommon: Anaphylactoid reactions, feeling hot, fever, soreness, inflammation near the injection site, local phlebitic reaction

Rare: Fatigue

Very rare: Acute severe anaphylactic reactions

Not known: Influenza like illness whose 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 Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard, or search for MHRA Yellow Card in the Google Play or Apple App Store.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.