EXJADE is not recommended in patients with severe hepatic impairment as it has not been studied in such patients. Treatment has been initiated only in patients with baseline liver transaminase levels up to 5 times the upper limit of the normal range (see section 5.2).

In patients with a short life expectancy (e.g. high-risk myelodysplastic syndromes), especially when co-morbidities could increase the risk of adverse events, the benefit of EXJADE might be limited and may be inferior to risks. As a consequence, treatment with EXJADE is not recommended in these patients.

Caution should be used in elderly patients due to a higher frequency of adverse reactions (in particular, diarrhoea).

Gastrointestinal

Upper gastrointestinal ulceration and haemorrhage have been reported in patients, including children and adolescents, receiving EXJADE. Multiple ulcers have been observed in some patients (see section 4.8). There have been reports of fatal gastrointestinal haemorrhages, especially in elderly patients who had haematological malignancies and/or low platelet counts. Physicians and patients should remain alert for signs and symptoms of gastrointestinal ulceration and haemorrhage during EXJADE therapy and promptly initiate additional eva luation and treatment if a serious gastrointestinal adverse reaction is suspected. Caution should be exercised in patients who are taking EXJADE in combination with substances that have known ulcerogenic potential, such as NSAIDs, corticosteroids, or oral bisphosphonates, in patients receiving anticoagulants and in patients with platelet counts below 50,000/mm3 (50 x 109/l) (see section 4.5).

Skin disorders

Skin rashes may appear during EXJADE treatment. The rashes resolve spontaneously in most cases. When interruption of treatment may be necessary, treatment may be reintroduced after resolution of the rash, at a lower dose followed by gradual dose escalation. In severe cases this reintroduction could be conducted in combination with a short period of oral steroid administration.

Hypersensitivity reactions

Cases of serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving EXJADE, with the onset of the reaction occurring in the majority of cases within the first month of treatment (see section 4.8). If such reactions occur, EXJADE should be discontinued and appropriate medical intervention instituted.

Vision and hearing

Auditory (decreased hearing) and ocular (lens opacities) disturbances have been reported (see section 4.8). Auditory and ophthalmic testing (including fundoscopy) is recommended before the start of treatment and at regular intervals thereafter (every 12 months). If disturbances are noted during the treatment, dose reduction or interruption may be considered.

Blood disorders

There have been post-marketing reports of leukopenia, thrombocytopenia or pancytopenia, or aggravation of these cytopenias in patients treated with EXJADE. Most of these patients had pre-existing haematological disorders that are frequently associated with bone marrow failure. However, a contributory or aggravating rol