其 他 安 全 警 示
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| The United Kingdom: Hydroxychloroquine and chloroquine: increased risk of cardiovascular events when used with macrolide antibiotics; reminder of psychiatric reactions (English only) |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces that an observational study in patients with rheumatoid arthritis has shown that co-administration of azithromycin with hydroxychloroquine is associated with an increased risk of cardiovascular events and cardiovascular mortality.
An observational retrospective study published in Aug 2020 compared records of adverse events in patients initiated on hydroxychloroquine alone with those in patients initiated on sulfasalazine alone for rheumatoid arthritis. The same study compared severe adverse events associated with use of hydroxychloroquine plus azithromycin with those associated with use of hydroxychloroquine plus amoxicillin. The study showed that in a short-term period (up to 30 days) after first use of hydroxychloroquine treatment in combination with azithromycin there was an increased risk of angina or chest pain, heart failure, and cardiovascular mortality compared with the combination of hydroxychloroquine and amoxicillin. No excess risk of severe adverse events was identified in the short-term period of hydroxychloroquine alone (compared with sulfasalazine), but longer-term use past 30 days was associated with increased cardiovascular mortality. Although the mechanism of the observed effects was not examined in detail by the study, it has been proposed that events could be caused by cumulative effects of hydroxychloroquine and azithromycin on the QT interval, potentiating arrhythmias and cardiac death, or through other additive cardiotoxic effects more generally.
A national review of safety data by the Pharmacovigilance Expert Advisory Group of the Commission on Human Medicines considered these data. The review recommended that the product information for hydroxychloroquine and systemic azithromycin medicines should be amended to include new warnings and advice on these risks. Due to the similar safety profiles, the risks seen with concurrent use of hydroxychloroquine and azithromycin are considered to apply to concurrent use of hydroxychloroquine and other systemic macrolide antibiotics (clarithromycin or erythromycin) and to use of chloroquine with systemic macrolide antibiotics. As such, the review recommended that similar warnings should also be added to the product information for chloroquine and for systemic clarithromycin or erythromycin. These warnings are not being introduced for topical macrolide products, as these products are used at lower doses and with very limited potential for systemic exposure, and do not list cardiovascular events as potential adverse effects associated with their use.
Hydroxychloroquine and chloroquine have been previously associated with psychiatric reactions, including reports of depression, anxiety, hallucinations, and psychosis. In Nov 2020, a European safety review recommended updates to the warnings for hydroxychloroquine and chloroquine medicines to include a range of reported psychiatric reactions, including rare cases of suicidal behaviour. The review noted that when psychiatric events occurred, they were typically within the first month of treatment. Events have been reported in patients with no previous history of psychiatric disorders. Information about these reactions have been added to the Summary of Product Characteristics and Patient Information Leaflets for hydroxychloroquine and chloroquine.
Advice for healthcare professionals:
- An observational study has shown that co-administration of azithromycin with hydroxychloroquine in patients with rheumatoid arthritis is associated with an increased risk of cardiovascular events (including angina or chest pain and heart failure) and cardiovascular mortality.
- Carefully consider the benefits and risks before prescribing systemic azithromycin or other systemic macrolide antibiotics (erythromycin or clarithromycin) to patients being treated with hydroxychloroquine or chloroquine.
- If there is a clinical need to prescribe systemic macrolide antibiotics with hydroxychloroquine or chloroquine, use caution in patients with risk factors for cardiac events and follow advice in the product information for each medicine.
- Be vigilant for psychiatric reactions associated with hydroxychloroquine or chloroquine, especially in the first month of treatment; events have been reported in patients with no prior history of psychiatric disorders.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/hydroxychloroquine-chloroquine-increased-risk-of-cardiovascular-events-when-used-with-macrolide-antibiotics-reminder-of-psychiatric-reactions
In Hong Kong, there are 5 registered pharmaceutical products containing hydroxychloroquine. All products are prescription-only medicines. There is no registered pharmaceutical product containing chloroquine. So far, the Department of Health (DH) has received 4 cases of adverse drug reaction related to hydroxychloroquine, but these cases were not related to cardiac and psychiatric reactions. The DH has not received any case of adverse drug reaction related to chloroquine.
Related news on the risk of heart rhythm problems associated with the use of hydroxychloroquine and chloroquine (particularly in combination with other drugs that have similar effects on the heart, such as the antibiotic azithromycin) was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 24 Apr 2020, with the latest update posted on 16 Jun 2020.
Related news on the risk of psychiatric disorders associated with the use of hydroxychloroquine and chloroquine was previously issued by European Medicines Agency, and was posted on the Drug Office website on 28 Nov 2020. Letters to inform local healthcare professionals were issued by the DH on 30 Nov 2020.
As previously reported, the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/Wednesday, Feb 16, 2022
Issued at HKT 14:30
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