Feburic Adverse Reactions

Summary of the safety profile: The most commonly reported adverse reactions in clinical trials (4,072 subjects treated at least with a dose from 10 mg to 300 mg) and post-marketing experience in gout patients are gout flares, liver function abnormalities, diarrhoea, nausea, headache, rash and oedema. These adverse reactions were mostly mild or moderate in severity. Rare serious hypersensitivity reactions to febuxostat, some of which were associated to systemic symptoms, and rare events of sudden cardiac death, have occurred in the post-marketing experience.
Tabulated list of adverse reactions: Common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and rare (≥ 1/10,000 to < 1/1,000) adverse reactions occurring in patients treated with febuxostat are listed as follows.
The frequencies are based on studies and post-marketing experience in gout patients.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 2.)

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Description of selected adverse reactions: Rare serious hypersensitivity reactions to febuxostat, including Stevens-Johnson Syndrome, Toxic epidermal necrolysis and anaphylactic reaction/shock, have occurred in the post-marketing experience. Stevens-Johnson Syndrome and Toxic epidermal necrolysis are characterised by progressive skin rashes associated with blisters or mucosal lesions and eye irritation. Hypersensitivity reactions to febuxostat can be associated to the following symptoms: skin reactions characterised by infiltrated maculopapular eruption, generalised or exfoliative rashes, but also skin lesions, facial oedema, fever, haematologic abnormalities such as thrombocytopenia and eosinophilia, and single or multiple organ involvement (liver and kidney including tubulointerstitial nephritis) (see Precautions).
Gout flares were commonly observed soon after the start of treatment and during the first months. Thereafter, the frequency of gout flare decreases in a time-dependent manner. Gout flare prophylaxis is recommended (see Dosage & Administration and Precautions).
Tumor Lysis Syndrome: Summary of the safety profile: In the randomized, double-blind, Phase 3 pivotal FLORENCE (FLO-01) study comparing febuxostat with allopurinol (346 patients undergoing chemotherapy for haematologic malignancies and at intermediate-to-high risk of TLS), only 22 (6.4%) patients overall experienced adverse reactions, namely 11 (6.4%) patients in each treatment group. The majority of adverse reactions were either mild or moderate.
Overall, the FLORENCE trial did not highlight any particular safety concern in addition to the previous experience with Feburic in gout, with the exception of the following three adverse reactions (listed previously in Table 2).
Cardiac disorders: Uncommon: Left bundle branch block, sinus tachycardia.
Vascular disorders: Uncommon: haemorrhage.