|For this product there is no modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Undesirable effects may vary in their incidence depending on the dose received and also when given in combination with other therapeutic agents.The frequency categories assigned to the adverse drug reactions below are estimates: for most reactions, suitable data for calculating incidence are not available. Adverse drug reactions identified through post-marketing surveillance were considered to be rare or very rare. The following convention has been used for the classification of frequency:|
Adverse reactions in association with 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.
||≥1/100 and <1/10 (≥1% and <10%)
||≥1/1,000 and <1/100 (≥ 0.1% and <1%)
||≥1/10,000 and <1/1000 (≥ 0.01% and <0.1%)
1. Very rare reports have been received of thrombocytopenia, agranulocytosis and aplastic anaemia, particularly in individuals with impaired renal and/or hepatic function, reinforcing the need for particular care in this group of patients.2. Serious hypersensitivity reactions, including skin reactions associated with exfoliation, fever, lymphadenopathy, pseudo lymphoma, arthralgia, leucopenia and/or eosinophilia (DRESS) and Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), occur rarely (see Skin and subcutaneous tissue disorders). Associated vasculitis and tissue response may be manifested in various ways including hepato-splenomegaly, hepatitis, vanishing bile duct syndrome (destruction and disappearance of the intrahepatic bile ducts), renal impairment and, very rarely, seizures. Other organs may also be affected (e.g. liver, lungs, kidneys, pancreas, myocardium, and colon). 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 Allopurinol should be withdrawn IMMEDIATELY and PERMANENTLY.Rechallenge should not be undertaken in patients with hypersensitivity syndrome and SJS/TEN. 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.3. Angioimmunoblastic T-cell lymphoma has been described very rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of allopurinol.4. 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.5. Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity. 6. 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. The highest risk for SJS and TEN, or other serious hypersensitivity reactions, is within the first weeks of treatment. The best results in managing such reactions come from early diagnosis and immediate discontinuation of any suspect drug. After recovery from mild reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. Consideration should be given to screening for the presence of the HLA-B*58:01 allele before allopurinol is reintroduced. If the rash reoccurs, allopurinol should be PERMANENTLY withdrawn as more severe hypersensitivity reactions may occur (see Immune system disorders). If SJS/TEN, or other serious hypersensitivity reactions cannot be ruled out, DO NOT re-introduce allopurinol due to the potential for a severe or even fatal reaction. The clinical diagnosis of SJS/TEN, or other serious hypersensitivity reactions remain the basis for decision making. 7. Angioedema has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction.8. Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
|Table 1 Undesirable effects|
|System Organ Class||Frequency||Adverse reaction|
|Infections and infestations
|Blood and lymphatic system disorders
|Immune system disorders
||Angioimmunoblastic T-cell lymphoma3|
|Metabolism and nutrition disorders
|Nervous system disorders
|Ear and labyrinth disorders
Change of bowel habit
||Liver function test abnormal5|
||Hepatitis (including hepatic necrosis and
|Skin and subcutaneous tissue disorders
Hair colour changes
|Renal and urinary disorders
|Reproductive system and breast disorders
|General disorders and administration site conditions
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; e-mail: email@example.com.