ed Exjade because of hepatic abnormalities (drug-induced hepatitis in 2patients and increased serum transaminases in 2 additional patients). There have been postmarketing reports of hepatic failure, some with a fatal outcome, in patients treated with Exjade. Most of these events occurred in patients greater than 55years of age. Most reports of hepatic failure involved patients with significant comorbidities, including liver cirrhosis and multiorgan failure. Serum transaminases and bilirubin should be monitored before the initiation of treatment, every 2 weeks during the first month and monthly thereafter. Consider dose modifications or interruption of treatment for severe or persistent elevations.
5.3 Gastrointestinal
Fatal GI hemorrhages, especially in elderly patients who had advanced hematologic malignancies and/or low platelet counts, have been reported. Non-fatal upper GI irritation, ulceration and hemorrhage have been reported in patients, including children and adolescents, receiving Exjade [see Adverse Reactions(6.1)]. Physicians and patients should remain alert for signs and symptoms of GI ulceration and hemorrhage during Exjade therapy and promptly initiate additional eva luation and treatment if a serious GI adverse event is suspected. Use caution when administering Exjade in combination with drugs that have ulcerogenic or hemorrhagic potential, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, oral bisphosphonates, or anticoagulants.
5.4 Cytopenias
There have been postmarketing reports (both spontaneous and from clinical trials) of cytopenias, including agranulocytosis, neutropenia and thrombocytopenia, in patients treated with Exjade. Some of these patients died. The relationship of these episodes to treatment with Exjade is uncertain. Most of these patients had preexisting hematologic disorders that are frequently associated with bone marrow failure [see Adverse Reactions(6.2)]. Monitor blood counts regularly. Consider interrupting treatment with Exjade in patients who develop unexplained cytopenia. Reintroduction of therapy with Exjade may be considered, once the cause of the cytopenia has been elucidated.
5.5 Hypersensitivity
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 Adverse Reactions(6.2)].If reactions are severe, discontinue Exjade and institute appropriate medical intervention.
5.6 Rash
Rashes may occur during Exjade (deferasirox) treatment. For rashes of mild to moderate severity, Exjade may be continued without dose adjustment, since the rash often resolves spontaneously. In severe cases, Exjade may be interrupted. Reintroduction at a lower dose with escalation may be considered in combination with a short period of oral steroid administration. Erythema multiforme has been reported during Exjade treatment.
5.7 Co-morbiditiesClinical trials to demonstrate increased survival or to confirm clinical benefit have not been completed. Exjade has been shown to decrease serum ferritin and liver iron concentration in clinical trials. Consider the importance of these factors as well as individual patient factors and the prognosis associated with any underlying conditions before initiation of Exjade therapy [see Contraindications (4)].
In postmar
