Other safety alerts
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| Singapore: Allopurinol-induced serious cutaneous adverse reactions and the role of genotyping |
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The Singapore Health Sciences Authority (HSA), together with the Ministry of Health (MOH), have jointly issued a Dear Healthcare Professional Letter (DHCPL) on 23 March 2016 to remind healthcare professionals of the risk of allopurinol-induced serious cutaneous adverse reactions (SCAR), and inform on the role of genotyping prior to the initiation of allopurinol. This article shares the summary of evidence presented on allopurinol-induced SCAR, genetic associations reported and the role of genotyping prior to therapy initiation.
Allopurinol is an efficacious urate-lowering therapy (ULT) which has been registered in Singapore since 1989 and is recommended as first-line therapy for gout patients who have two or more gouty attacks per year, presence of tophus, radiographic changes of gout, and urolithiasis. Globally, increasing incidence but sub-optimal management of gout has been reported.
Allopurinol, while effective in treating chronic gout, is associated with rare and potentially fatal SCAR, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Allopurinol is one of the leading causes of drug-induced SCAR reported to HSA. From 2010 to 2014, HSA received 70 cases of allopurinol-induced SCAR, seven of which were fatal. A review of local SCAR reports received by HSA and the published local and international studies found that the majority of SCAR occurred within three months, with a median onset of 3-4 weeks upon the initiation of therapy. Risk factors of allopurinol-induced SCAR include HLA-B*5801 allele, starting dose of allopurinol and renal impairment. A low starting dose, no greater than 100mg per day, for gout has been recommended to minimise the risk of allopurinol-induced SCAR.
The recommendations on the use and monitoring of allopurinol and the consideration for HLA-B*5801 allele genotyping are based on the findings of a HSA-initiated, local, multi-centre, case-control study conducted at Singapore General Hospital, National University Hospital, Changi General Hospital and the National Skin Centre. Details can be found at the HSA’s website.
HSA has received nine allopurinol-induced SCAR reports between March and August 2016, since the issuance of the DHCPL. Majority of these cases reported the use of allopurinol for gout in Chinese patients.
In view of the seriousness and fatalities reported with allopurinol-induced SCAR, healthcare professionals are advised to use allopurinol with caution; start at a low dose, titrate and monitor accordingly based on clinical indications.
As early signs of rash and skin reactions may be indicative of a more serious reaction such as SCAR, healthcare professionals are advised to educate their patients on early recognition of allergic reactions, the importance of prompt withdrawal of the drug at the first sign of rash and to seek medical advice.
While genotyping is not required as standard of care for new patients starting allopurinol, doctors may consider genotyping patients who have other pre-existing risk factors for allopurinol-induced SCAR such as renal impairment and to identify the patients who are at a greater risk of allopurinol-induced SCAR. While it is likely that patients who have tested negative for this allele may not develop allopurinol-induced SCAR, the possibility of developing allopurinol-induced SCAR due to other risk factors cannot be ruled out. Genetic testing, when ordered for at-risk patients, should not substitute for appropriate clinical vigilance and patient management.
Please refer to the following website in HSA for details:
http://www.hsa.gov.sg/content/hsa/../allopurinol-inducedseriouscutaneousadversereactionsandtheroleofg.html
In Hong Kong, there are 45 registered pharmaceutical products containing allopurinol. All these products are pharmacy only medicines. Related news was previously issued by HSA, and was posted on the Drug Office website on 24 March 2016. So far, the Department of Health (DH) has received two adverse drug reaction cases in connection with allopurinol, and both of them involved SJS. For locally registered products, it is a labelling requirement that an appropriate statement concerning the product’s potential to cause serious cutaneous reactions must be included in the package insert or label, e.g. “Allopurinol should be discontinued at the first appearance of skin rash or other signs which may indicate an allergic reaction. In some instances, a skin rash may be followed by more severe reactions such as exfoliative, urticarial and purpuric lesions as well as Stevens-Johnson syndrome”. DH will remain vigilant on the safety of medicines containing allopurinol.
Ends/ Thursday, September 22, 2016
Issued at HKT 16:00
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