其 他 安 全 警 示
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| The United Kingdom: Febuxostat (Adenuric): increased risk of cardiovascular death and all-cause mortality in clinical trial in patients with a history of major cardiovascular disease (English only) |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces that findings from a phase 4 clinical study (the CARES study) in patients with gout and a history of major cardiovascular disease show a higher risk for cardiovascular-related death and for all-cause mortality in patients assigned to febuxostat than in those assigned to allopurinol.
The CARES study (ClinicalTrials.gov NCT01101035) was a phase 4, randomised, double-blind, non-inferiority trial that recruited patients with gout and a history of major cardiovascular disease from the USA, Canada and Mexico. The primary endpoint was time to first occurrence of major adverse cardiovascular events (MACE), a composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, and unstable angina with urgent coronary revascularisation. Outcomes analysis was for patients who had received at least 1 dose of the randomly allocated treatment.
Overall 57% of patients prematurely discontinued trial treatment and 45% of patients did not complete all trial visits; 6,190 patients were followed for a median of 32 months. The median duration of exposure was 728 days for patients in febuxostat group (n=3,098) and 719 days in allopurinol group (n=3,092). The primary MACE endpoint occurred at similar rates in the febuxostat and allopurinol treatment groups (10.8% versus 10.4% of patients, respectively; hazard ratio 1.03, 95% confidence interval [CI] 0.87–1.23).
In secondary analysis, the incidence of cardiovascular deaths was higher in the group assigned to febuxostat than in the group assigned to allopurinol (4.3% versus 3.2%, respectively; hazard ratio 1.34, 95% CI 1.03–1.73). The incidence of all-cause mortality was also higher in patients assigned to febuxostat than in those assigned to allopurinol (7.8% versus 6.4% respectively; hazard ratio 1.22, 95% CI 1.01–1.47), which was mainly driven by the higher rate of cardiovascular deaths in the febuxostat group.
An EU review of the findings of the CARES study and their impact on the safety of febuxostat has recommended avoiding febuxostat in patients with a history of major cardiovascular disease. A letter has been sent to relevant healthcare professionals. The Summary of Product Characteristics and Patient Information Leaflet is being updated to reflect the CARES study results.
Healthcare professionals are advised:
- Avoid treatment with febuxostat in patients with pre-existing major cardiovascular disease (for example, myocardial infarction, stroke, or unstable angina), unless no other therapy options are appropriate.
- Note the clinical guidelines for gout, which recommend treatment with febuxostat only when allopurinol is not tolerated or contraindicated.
Patients taking febuxostat are advised to contact their healthcare professional if they are concerned about their medicine.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/febuxostat-adenuric-increased-risk-of-cardiovascular-death-and-all-cause-mortality-in-clinical-trial-in-patients-with-a-history-of-major-cardiovascular-disease
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 the US Food and Drug Administration, and was posted on the Drug Office website on 16 Nov 2017 and 22 Feb 2019. Letters to inform local healthcare professionals were issued by the 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. The DH will remain vigilant on safety update of the drug issued by other overseas drug regulatory authorities.
Ends/Thursday, Jul 18, 2019
Issued at HKT 17:00
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