Systemic and inhaled fluoroquinolones: small increased risk of aortic aneurysm and dissection; advice for prescribing in high-risk patients

In patients at risk for aortic aneurysm and dissection, fluoroquinolones should only be used after careful assessment of the benefits and risks and after consideration of other therapeutic options.

Advice for healthcare professionals:

  • systemic (by mouth or injection) and inhaled fluoroquinolones may be associated with a small increased risk of aortic aneurysm and dissection, particularly in older patients

  • fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients at risk for aortic aneurysm and dissection

  • Conditions predisposing to aortic aneurysm and dissection include:
    • a family history of aneurysm disease
    • diagnosis with pre-existing aortic aneurysm and/or aortic dissection
    • other risk factors or conditions predisposing for aortic aneurysm and dissection (for example, Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet’s disease, hypertension, and known atherosclerosis)
  • advise patients, particularly elderly people and those at risk, about rare events of aortic aneurysm and dissection and of the importance of seeking immediate medical attention in case of sudden-onset severe abdominal, chest or back pain

  • report suspected adverse drug reactions to fluoroquinolone antibiotics on the Yellow Card website or via the Yellow Card app (download it from the Apple App Store, or Google Play Store)

Data suggesting increased risk of aortic aneurysm and dissection

Fluoroquinolones are antibiotics authorised for serious, life-threatening bacterial infections (see list of fluoroquinolone antibiotics below).

Data from epidemiologic and non-clinical studies indicate an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones.

Epidemiological studies suggest an increased risk of aortic aneurysm and dissection with fluoroquinolone usage, particularly in older patients. One study1 reported a rate of aortic aneurysm or dissection of 1.2 cases per 1000 person-years among fluoroquinolone treatment episodes versus 0.7 cases per 1000 person-years among amoxicillin treatment episodes, corresponding to an estimated absolute difference of 82 (95% confidence interval 15–181) cases of aortic aneurysm or dissection by 60 days per 1 million treatment episodes. Another study2 of patients aged 65 years and older in Canada reported a rate of aortic aneurysms diagnosed in hospital and emergency departments as 3.5 per 1000 person-years for patients currently using fluoroquinolones versus 1.3 per 1000 person-years for patients not using fluoroquinolones.

In the studies, the increased risk for aortic aneurysm was seen within the first 1 to 2 months of treatment with systemic fluoroquinolones.1 2 The data do not allow for differentiation between risk for different fluoroquinolones or durations of treatment. These findings indicate that systemic or inhaled fluoroquinolones might contribute to aortic aneurysm and dissection, in particular in patients with pre-existing risk factors.

About aortic aneurysm and dissection

Aortic aneurysm and dissection are rare events, occurring in about 3–30 of 100,000 persons per year in the general population. Risk of aortic aneurism is increased in the presence of risk factors such as family history of aneurysm disease; pre-existing aortic aneurysm and/or aortic dissection; Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet’s disease, or hypertension; or known atherosclerosis.

While most abdominal aortic aneurysms are asymptomatic, some people describe persistent stomach, chest and/or lower back pain. Aortic dissection is usually accompanied by sudden, severe abdominal, chest, or back pain.

If initiating a course of a fluoroquinolone antibiotic advise patients, particularly elderly people and those at risk, of the need to seek immediate medical attention if they develop sudden, severe pain in the abdomen, chest or lower back since this may suggest a life-threatening aortic dissection (see letter to healthcare professionals).

Fluoroquinolone medicines available in UK:

  • Ciprofloxacin
  • Levofloxacin
  • Moxifloxacin
  • Ofloxacin

Recommendations on restrictions on use

In October 2018 EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) recommended restricting the use of fluoroquinolone and quinolone antibiotics (by mouth, injection or inhalation) following a review of disabling and potentially long-lasting side effects reported with these medicines. The recommendation is now subject to further EU consideration and will take effect once a European Commission decision is issued. We will communicate the necessary actions to UK healthcare professionals following this Commission decision, which is expected in early 2019.

Report suspected adverse drug reactions via the Yellow Card scheme

Please continue to report any suspected adverse drug reactions via the Yellow Card Scheme. Remember only a suspicion is needed to report – if in doubt, please complete a Yellow Card.

Healthcare professionals, patients, and caregivers can report suspected side effects via the Yellow Card website or via the Yellow Card app. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices.

You can also use the app to access the latest safety information from the MHRA about medicines and medical devices on the Newsfeed. Search for medicines to see details of Yellow Card reports others have made. Medicines of interest can also be added to a Watch List to receive news and alerts about new side effects and safety advice as it emerges.

Article citation: Drug Safety Update volume 12, issue 4: November 2018: 2.

Published 14 November 2018