其 他 安 全 警 示
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| Singapore: Risk of cardiovascular events with febuxostat (English only) |
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The Health Sciences Authority (HSA) announces that recent findings from a completed post-market study have further characterised the cardiovascular (CV) profile of febuxostat by showing that gout patients with a pre-existing major CV disease treated with febuxostat had a statistically significant higher risk of CV death and all-cause mortality compared to those on allopurinol. Febuxostat (Feburic®, Astellas Pharma Singapore Pte Ltd) has been registered in Singapore since 2016.
Concerns about the CV risk of febuxostat first arose during the pre-market phase, where a numerical excess of serious CV events (including CV death, non-fatal myocardial infarction and non-fatal stroke) was observed among febuxostat-treated subjects compared to allopurinol-treated subjects (1.3 vs 0.3 events per 100 patient-years) in the Phase 3 clinical studies, APEX and FACT. As a result, the product labelling for febuxostat had included warnings on possible CV events when it was first approved and the United States Food and Drug Administration had requested for the conduct of a large post-market clinical trial to further evaluate its CV safety. This study, known as the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) study, was recently completed in 2017.
The CARES study was a phase 4, multi-centre, randomised, double-blind CV outcomes study that involved 6,190 patients with gout who were treated with either febuxostat or allopurinol. The patients also had an established major CV disease, including a history of myocardial infarction, hospitalisation for unstable angina or transient ischaemic attack, stroke, peripheral vascular disease, or diabetes mellitus with evidence of microvascular or macrovascular disease. After a median follow-up of 32 months, the study found a statistically significant higher risk of CV-related death and all-cause mortality in the febuxostat group compared to the allopurinol group. The primary endpoint, which was a composite of CV death, non-fatal myocardial infarction, non-fatal stroke, or unstable angina with urgent revascularisation, occurred at similar rates between both groups.
The imbalances in the incidence of serious CV events between febuxostat- and allopurinol-treated patients observed from the pre-market studies are currently highlighted in the local package insert (PI) of Feburic® to warn healthcare professionals about the potential risk of serious CV events, including CV deaths. The PI also included advice that treatment with febuxostat in patients with ischaemic heart disease or congestive heart failure is not recommended. In response to the CARES study, the company has updated the local PI to highlight the study findings and to recommend that caution should be exercised for exacerbation and/or onset of CV disease when administering febuxostat.
Healthcare professionals are advised to take into consideration the above information when prescribing febuxostat, particularly to patients with a history of CV disease. In patients with ischaemic heart disease or congestive heart failure, treatment with febuxostat is not recommended.
Please refer to the following website in HSA for details:
http://www.hsa.gov.sg/announcements/safety-alert/risk-of-cardiovascular-events-with-febuxostat
In Hong Kong, there are 2 registered pharmaceutical products containing febuxostat, namely Feburic Tablets 80mg (HK-61185) and Feburic Tablets 120mg (HK-61186). Both products are registered by Astellas Pharma Hong Kong Company Limited, and are prescription-only medicines. So far, the Department of Health (DH) has received one case of adverse drug reaction related to febuxostat, but this case is not related to death.
Related news was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 16 Nov 2017, with the latest update posted on 5 Nov 2019. Letters to inform local healthcare professionals were issued by DH on 22 Feb 2019. In Jun 2019, the Registration Committee of the Pharmacy and Poisons Board discussed the matter and noted that the package insert of the local products had included relevant safety information. DH will remain vigilant on safety update of the drug issued by other overseas drug regulatory authorities.
Ends/Wednesday, Dec 11, 2019
Issued at HKT 16:00
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