Background of Safety Issue

The European Medicines Agency (EMA) has requested the product registration holders of fluoroquinolones (systemic and inhaled) to update the product information to include the risk of aortic aneurysm and dissection. This measure was undertaken following three (3) epidemiological studies and one (1) non-clinical study in which the association of fluoroquinolones with the risk of aortic aneurysm and dissection could not be excluded. The United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) and the French National Agency for Medicines and Health Products Safety (ANSM) have also issued similar safety alerts to healthcare professionals.

The epidemiological studies reported an increased risk of aortic aneurysm and dissection following the usage of fluoroquinolones, particularly in the elderly. Therefore, fluoroquinolones should only be used after careful assessment of the benefits and risks, and taking into consideration other therapeutic options in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissection, or in presence of other risk factors for aortic aneurysm and dissection. Patients should be advised to immediately consult a physician should there be any symptoms of severe abdominal, chest or back pain¹.

The mechanism by which fluoroquinolones may induce aortic aneurysm and dissection is unknown. However, it was postulated that fluoroquinolones can induce the expression of matrix metalloproteinases, which is a group of enzymes that degrade the extracellular matrix. This may cause weakness of the aortic wall that may lead to aortic aneurysm and dissection².

Adverse Drug Reaction Reports

NPRA has received 1,093 reports with 2,066 adverse events suspected to be related to fluoroquinolone usage. There have been no reports regarding aortic aneurysm and dissection³. The most commonly reported adverse events were non-serious skin reactions such as pruritus, rash, urticaria and erythema.

A directive [Ruj. Kami: (9) dlm. BPFK/PPP/07/25 Jld. 3] has been issued by NPRA for updates to the local product packaging insert and consumer medication information leaflet (Risalah Maklumat Ubat untuk Pengguna) related to this safety issue. Please refer to the directive for more information.

References:

1. European Medicines Agency (2018). PRAC recommendations on signals: Adopted at the 3-6 September 2018 PRAC meeting. EMA/PRAC/595691/2018.
2. Pasternak B., et. al (2018). Fluoroquinolone use and risk of aortic aneurysm and dissection:nationwide cohort study. The British Medical Journal (BMJ). 360:k678
3. The Malaysian Adverse Drug Reaction Database, NPRA [Accessed: July 2018].

DISCLAIMER
This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.