|For this product there is no modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Undesirable effects may vary in their incidence depending on the dose received and also when given in combination with other therapeutic agents.The frequency categories assigned to the adverse drug reactions below are estimates: for most reactions, suitable data for calculating incidence are not available. Adverse drug reactions identified through post-marketing surveillance were considered to be rare or very rare. The following convention has been used for the classification of frequency:|
Adverse reactions in association with Zyloric are rare in the overall treated population and mostly of a minor nature. The incidence is higher in the presence of renal and/or hepatic disorder.
≥1/100 and <1/10 (≥1% and <10%)
≥1/1000 and <1/100 (≥0.1% and <1%)
≥1/10,000 and <1/1000 (≥0.01% and <0.1%)
Very rare reports have been received of thrombocytopenia, agranulocytosis and aplastic anaemia, particularly in individuals with impaired renal and/or hepatic function, reinforcing the need for particular care in this group of patients.
Infections and infestations
Blood and lymphatic system disorders
Agranulocytosis, aplastic anaemia, thrombocytopenia
Serious hypersensitivity reactions, including skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia and/or eosinophilia including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis occur rarely (see Skin and subcutaneous tissue disorders). Associated vasculitis and tissue response may be manifested in various ways including hepatitis, renal impairment and very rarely, seizures. Very rarely acute anaphylactic shock has been reported. If such reactions do occur, it may be at any time during treatment, Zyloric should be withdrawn immediately and permanently.Corticosteroids may be beneficial in overcoming hypersensitivity skin reactions. When generalised hypersensitivity reactions have occurred, renal and/or hepatic disorder has usually been present particularly when the outcome has been fatal.Angioimmunoblastic lymphadenopathy has been described very rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of Zyloric.
Immune system disorders
Skin reactions are the most common reactions and may occur at any time during treatment. They may be pruritic, maculopapular, sometimes scaly, sometimes purpuric and rarely exfoliative, such as Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). Zyloric should be withdrawn immediately should such reactions occur. After recovery from mild reactions, Zyloric may, if desired, be re-introduced at a small dose (e.g. 50mg/day) and gradually increased. If the rash recurs, Zyloric should be permanently withdrawn as more severe hypersensitivity may occur (see Immune system disorders).The HLA-B*5801 allele has been has been identified as a genetic risk factor for allopurinol associated SJS/TEN in retrospective, case-control, pharmacogenetic studies in patients of Han Chinese, Japanese and European descent. Up to 20-30% of some Han Chinese, African and Indian populations carry the HLA-B*5801 allele whereas only 1-2% of Northern European, US European and Japanese patients are estimated to be HLA-B*5801 carriers. However, the use of genotyping as a screening tool to make decisions about treatment with allopurinol has not been established.The clinical diagnosis of SJS/TEN remains the basis for decision making. If such reactions occur at any time during treatment, allopurinol should be withdrawn immediately and permanently.Angioedema has been reported to occur with and without signs and symptoms of a more generalised hypersensitivity reaction.
Metabolism and nutrition disorders
Diabetes mellitus, hyperlipidaemia
Nervous system disorders
Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion
Cataract, visual disorder, macular changes
Ear and labyrinth disorders
Recurrent haematemesis, steatorrhoea, stomatitis, changed bowel habit
In early clinical studies, nausea and vomiting were reported. Further reports suggest that this reaction is not a significant problem and can be avoided by taking Zyloric after meals.
Asymptomatic increases in liver function tests
Hepatitis (including hepatic necrosis and granulomatous hepatitis)
Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity.
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome/toxic epidermal necrolysis
Angioedema, fixed drug eruption, alopecia, discoloured hair
Fever has been reported to occur with and without signs and symptoms of a more generalised Zyloric hypersensitivity reaction (see Immune system disorders).
Renal and urinary disorders
Reproductive system and breast disorders
Male infertility, erectile dysfunction, gynaecomastia
General disorders and administration site conditions
Oedema, general malaise, asthenia, fever