Other considerations

Monthly monitoring of serum ferritin is recommended in order to assess the patient's response to therapy (see section 4.2). If serum ferritin falls consistently below 500 μg/l, an interruption of treatment should be considered.

The results of the tests for serum creatinine, serum ferritin and serum transaminases should be recorded and regularly assessed for trends. The results should also be noted in the provided patient's booklet.

In one clinical study, growth and sexual development of paediatric patients treated with EXJADE for up to 5 years were not affected. However, as a general precautionary measure in the management of paediatric patients with transfusional iron overload, body weight, height and sexual development should be monitored at regular intervals (every 12 months).

Cardiac dysfunction is a known complication of severe iron overload. Cardiac function should be monitored in patients with severe iron overload during long-term treatment with EXJADE.

Each tablet contains 136 mg lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or severe lactase deficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

 The safety of EXJADE in combination with other iron chelators has not been established. Therefore, it must not be combined with other iron chelator therapies (see section 4.3).

The concomitant administration of EXJADE with substances that have known ulcerogenic potential, such as NSAIDs (including acetylsalicylic acid at high dosage), corticosteroids or oral bisphosphonates may increase the risk of gastrointestinal toxicity (see section 4.4). The concomitant administration of EXJADE with anticoagulants may also increase the risk of gastrointestinal haemorrhage. Close clinical monitoring is required when deferasirox is combined with these substances.

The bioavailability of deferasirox was increased to a variable extent when taken along with food. EXJADE must therefore be taken on an empty stomach at least 30 minutes before food, preferably at the same time each day (see sections 4.2 and 5.2).

Deferasirox metabolism depends on UGT enzymes. In a healthy volunteer study, the concomitant administration of EXJADE (single dose of 30 mg/kg) and the potent UGT inducer, rifampicin, (repeated dose of 600 mg/day) resulted in a decrease of deferasirox exposure by 44% (90% CI: 37% - 51%). Therefore, the concomitant use of EXJADE with potent UGT inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital, ritonavir) may result in a decrease in EXJADE efficacy. The patient's serum ferritin should be monitored during and after the combination, and the dose of EXJADE adjusted if necessary.

Cholestyramine significantly reduced the deferasirox exposure in a mechanistic study to determine the degree of enterohepatic recycling (see section 5.2).

In a healthy volunteer study, the concomitant administration of EXJADE and midazolam (a CYP3A4 probe substrate) resulted in a decrease of midazolam exposure by 17% (90% CI: 8% - 26%). In the clinical setting, this effect may be more pronounced. Therefore, due to a possible decrease in efficacy, caution should be exercised when deferasirox i