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4.4 Special Warnings and Precautions for Use
Zyloric should be withdrawn immediately if a skin rash or other evidence of sensitivity occurs as this could result in more serious hypersensitivity reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis) (see Adverse Reactions – Immune system disorders and Skin and subcutaneous tissue disorders).
Reduced doses should be used in patients with hepatic or renal impairment. Patients under treatment for hypertension or cardiac insufficiency, for example with diuretics or ACE inhibitors, may have some concomitant impairment of renal function and allopurinol should be used with care in this group.
Asymptomatic hyperuricaemia per se is generally not considered an indication for use of Zyloric. Fluid and dietary modification with management of the underlying cause may correct the condition.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.
Allopurinol treatment should not be started until an acute attack of gout has completely subsided, as further attacks may be precipitated.
In the early stages of treatment with Zyloric, as with uricosuric agents, an acute attack of gouty arthritis may be precipitated. Therefore it is advisable to give prophylaxis with a suitable anti-inflammatory agent or colchicine for at least one month. The literature should be consulted for details of appropriate dosage and precautions and warnings.
If acute attacks develop in patients receiving allopurinol, treatment should continue at the same dosage while the acute attack is treated with a suitable anti-inflammatory agent.
In conditions where the rate of urate formation is greatly increased (e.g. malignant disease and its treatment, Lesch-Nyhan Syndrome) the absolute concentration of xanthine in urine could, in rare cases, rise sufficiently to allow deposition in the urinary tract. This risk may be minimised by adequate hydration to achieve optimal urine dilution.
Adequate therapy with Zyloric will lead to dissolution of large uric acid renal pelvic stones, with the remote possibility of impaction in the ureter.
4.8 Undesirable Effects
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.
Skin and hypersensitivity reactions These 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. 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 reactions may occur. Skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia and/or eosinophilia including Stevens-Johnson syndrome and toxic epidermal necrolysis occur rarely. Associated vasculitis and tissue response may be manifested in various ways including hepatitis, renal impairment and, very rarely, seizures. 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. Very rarely acute anaphylactic shock has been reported. Angioimmunoblastic lymphadenopathy Angioimmunoblastic lymphadenopathy has been described rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of Zyloric. Hepatic function Rare cases of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity. Gastrointestinal disorder 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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Skin and hypersensitivity reactions
These 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. 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 reactions may occur. Skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia and/or eosinophilia including Stevens-Johnson syndrome and toxic epidermal necrolysis occur rarely. Associated vasculitis and tissue response may be manifested in various ways including hepatitis, renal impairment and, very rarely, seizures. 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. Very rarely acute anaphylactic shock has been reported. Angioimmunoblastic lymphadenopathy Angioimmunoblastic lymphadenopathy has been described rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of Zyloric. Hepatic function Rare cases of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity. Gastrointestinal disorder 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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
These 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. 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 reactions may occur.
Skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia and/or eosinophilia including Stevens-Johnson syndrome and toxic epidermal necrolysis occur rarely. Associated vasculitis and tissue response may be manifested in various ways including hepatitis, renal impairment and, very rarely, seizures. 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. Very rarely acute anaphylactic shock has been reported. Angioimmunoblastic lymphadenopathy Angioimmunoblastic lymphadenopathy has been described rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of Zyloric. Hepatic function Rare cases of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity. Gastrointestinal disorder 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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia and/or eosinophilia including Stevens-Johnson syndrome and toxic epidermal necrolysis occur rarely. Associated vasculitis and tissue response may be manifested in various ways including hepatitis, renal impairment and, very rarely, seizures. 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. Very rarely acute anaphylactic shock has been reported. Angioimmunoblastic lymphadenopathy Angioimmunoblastic lymphadenopathy has been described rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of Zyloric. Hepatic function Rare cases of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity. Gastrointestinal disorder 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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
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.
Very rarely acute anaphylactic shock has been reported. Angioimmunoblastic lymphadenopathy Angioimmunoblastic lymphadenopathy has been described rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of Zyloric. Hepatic function Rare cases of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity. Gastrointestinal disorder 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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Very rarely acute anaphylactic shock has been reported.
Angioimmunoblastic lymphadenopathy Angioimmunoblastic lymphadenopathy has been described rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of Zyloric. Hepatic function Rare cases of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity. Gastrointestinal disorder 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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Angioimmunoblastic lymphadenopathy
Angioimmunoblastic lymphadenopathy has been described rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of Zyloric. Hepatic function Rare cases of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity. Gastrointestinal disorder 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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Angioimmunoblastic lymphadenopathy has been described rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of Zyloric.
Hepatic function Rare cases of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity. Gastrointestinal disorder 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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Hepatic function
Rare cases of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity. Gastrointestinal disorder 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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Rare cases of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity.
Gastrointestinal disorder 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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Gastrointestinal disorder
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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea. Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
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. Recurrent haematemesis has been reported as an extremely rare event, as has steatorrhoea.
Blood and lymphatic system Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Blood and lymphatic system
Occasional 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. Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Occasional 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.
Miscellaneous The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
Miscellaneous
The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia. 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: Very common =1/10 (= 10%) Common =1/100 and < 1/10 (= 1% and <10%) Uncommon =1/1000 and <1/100 (=0.1% and <1%) Rare =1/10,000 and <1/1000 (=0.01% and < 0.1%) Very rare <1/10,000 (< 0.01%) Adverse reactions in association with allopurinol 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. Infections and infestations Very rare Furunculosis Blood and lymphatic system disorders Very rare Agranulocytosis, aplastic anaemia, thrombocytopenia 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. Immune system disorders Uncommon Hypersensitivity reactions Very rare Angioimmunoblastic lymphadenopathy 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. Allopurinol 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 allopurinol. Metabolism and nutrition disorders Very rare Diabetes mellitus, hyperlipidaemia Psychiatric disorders Very rare Depression Nervous system disorders Very rare Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion Eye disorders Very rare Cataract, visual disorder, macular changes Ear and labyrinth disorders Very rare Vertigo Cardiac disorders Very rare Angina, bradycardia Vascular disorders Very rare Hypertension Gastrointestinal disorders Uncommon Vomiting, nausea Very rare 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 allopurinol after meals. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests Rare Hepatitis (including hepatic necrosis and granulomatous hepatitis) Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. Skin and subcutaneous tissue disorders Common Rash Rare Stevens-Johnson syndrome/toxic epidermal necrolysis Very rare Angioedema, fixed drug eruption, alopecia, discoloured hair 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). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction. Renal and urinary disorders Very rare Haematuria, uraemia Reproductive system and breast disorders Very rare Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Very rare Oedema, general malaise, asthenia, fever Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
The following complaints, have been reported occasionally; fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, coma, depression, paralysis, paraesthesiae, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, diabetes mellitus, hyperlipaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, uraemia, haematuria, angioedema and gynaecomastia.
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:
Very common
=1/10 (= 10%)
Common
=1/100 and < 1/10 (= 1% and <10%)
Uncommon
=1/1000 and <1/100 (=0.1% and <1%)
Rare
=1/10,000 and <1/1000 (=0.01% and < 0.1%)
Very rare
<1/10,000 (< 0.01%)
Adverse reactions in association with allopurinol 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.
Infections and infestations
Furunculosis
Blood and lymphatic system disorders
Agranulocytosis, aplastic anaemia, thrombocytopenia
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.
Immune system disorders
Hypersensitivity reactions
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. Allopurinol should be withdrawn IMMEDIATELY AND PERMANENTLY.
Angioimmunoblastic lymphadenopathy has been described very rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of allopurinol.
Metabolism and nutrition disorders
Diabetes mellitus, hyperlipidaemia
Psychiatric disorders
Depression
Nervous system disorders
Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence, headache, taste perversion
Eye disorders
Cataract, visual disorder, macular changes
Ear and labyrinth disorders
Vertigo
Cardiac disorders
Angina, bradycardia
Vascular disorders
Hypertension
Gastrointestinal disorders
Vomiting, nausea
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 allopurinol after meals.
Hepatobiliary disorders
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
Rash
Stevens-Johnson syndrome/toxic epidermal necrolysis
Angioedema, fixed drug eruption, alopecia, discoloured hair
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).
Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions 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 allopurinol hypersensitivity reaction.
Renal and urinary disorders
Haematuria, uraemia
Reproductive system and breast disorders
Male infertility, erectile dysfunction, gynaecomastia
General disorders and administration site conditions
Oedema, general malaise, asthenia, fever
Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
New Individual SPC wsa previously a combined SPC
10. DATE OF REVISION OF THE TEXT
100mg: October 2006
300mg: November 2006
6.4 Special Precautions for Storage
Do not store above 25°C.
Store in the original package