Systemic and inhaled fluoroquinolones: small risk of heart valve regurgitation; consider other therapeutic options first in patients at risk

Fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients at risk for heart valve regurgitation (incompetence).

From:
Medicines and Healthcare products Regulatory Agency
Published
17 December 2020
Therapeutic area:
Infectious disease

Advice for healthcare professionals:

  • fluoroquinolones are authorised for use in serious, life-threatening bacterial infections
  • systemic (by mouth or injection) and inhaled fluoroquinolones have been associated with a small increased risk of heart valve regurgitation, with one retrospective case-control study suggesting a 2-fold increased relative risk with current oral fluroquinolone use compared with the risk with use of amoxicillin or azithromycin
  • fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in the following patients at risk:
    • patients with congenital heart valve disease or pre-existing heart valve disease
    • patients diagnosed with connective tissue disorders (for example, Marfan syndrome or Ehlers-Danlos syndrome)
    • patients with other risk factors or conditions predisposing for heart valve regurgitation (for example, hypertension, Turner’s syndrome, Behçet’s disease, rheumatoid arthritis, and infective endocarditis)
  • advise patients, especially those at risk, of the importance of seeking immediate medical attention if they experience:
    • a rapid onset of shortness of breath, especially when lying down flat in bed
    • swelling of the ankles, feet, or abdomen
    • new-onset heart palpitations
  • due to the small increased risk of aortic aneurysm and dissection, we have previously advised that fluoroquinolones should only be used after careful assessment of the benefits and risks in patients at risk of aneurysms and after consideration of other therapeutic options
  • fluoroquinolones have also been associated with disabling, long-lasting or potentially irreversible adverse reactions affecting musculoskeletal and nervous systems – treatment should be discontinued at the first signs of a serious adverse reaction, including tendon pain or inflammation
  • report suspected adverse drug reactions associated with fluoroquinolone antibiotics via the Yellow Card scheme

Fluoroquinolones: previous prescribing advice

Fluoroquinolones are antibiotics approved for serious, life-threatening bacterial infections. UK authorised medicines include ciprofloxacin, levofloxacin, moxifloxacin, and ofloxacin. As for all antibiotic medicines, consideration should be given to official guidance on the appropriate use of antibacterial agents.

Fluoroquinolones have previously been associated with a small increased risk of aortic aneurysm and dissection. We have previously advised that fluoroquinolones should only be used after careful assessment of the benefits and risks in patients at risk of these events and after consideration of other therapeutic options. Patients at risk include those with a family history or previous history of aneurysm disease or those with other risk factors or conditions predisposing for aortic aneurysm and dissection (including some conditions listed in the Advice section above).

Fluoroquinolones have also previously been associated with an increased risk of disabling and potentially long-lasting, irreversible side effects affecting the musculoskeletal and nervous system, most commonly tendonitis and tendon rupture. Tendon damage (especially to the Achilles tendon) can occur within 48 hours of starting fluoroquinolone treatment, but onset of symptoms and signs of the adverse reactions may be delayed several months after stopping treatment.

Following the review of these side effects, in 2019 the indications for all fluoroquinolones were restricted and new safety warnings introduced. These medicines should not be used for non-severe or self-limiting infections, non-bacterial conditions, or some mild to moderate infections unless other antibiotics that are commonly recommended are considered inappropriate. The Drug Safety Update from March 2019 provides further detail on the important prescribing recommendations.

New data suggesting increased risk of heart valve regurgitation

A European review has considered data from epidemiological and non-clinical studies indicating an increased risk of heart valve regurgitation after use of fluoroquinolones.

An epidemiological study suggested an increased risk of aortic and mitral regurgitation associated with fluoroquinolone usage.[footnote 1] The case-control study of US patient records retrospectively examined a cohort of 12,502 patients with valvular regurgitation (after excluding patients with other conditions that may be associated with valvulopathy). Prescriptions of oral fluoroquinolones were compared with those of amoxycillin within this group and within a control cohort of 125,020 people.

Patients with mitral or aortic regurgitation were nearly twice as likely to have been exposed to fluoroquinolones (2.4% of cases) than to amoxycillin (1.6% of cases). The study reported an adjusted rate ratio for current fluoroquinolones use versus amoxicillin use of 2.40 (95% CI 1.82 to 3.16) and versus current azithromycin use of 1.75 (95% CI 1.34 to 2.29).

A non-clinical study also reported that ciprofloxacin increases collagen degradation in heart muscle cells. These findings indicate that systemic or inhaled fluoroquinolones might contribute to heart valve regurgitation, particularly in patients with pre-existing risk factors.

The increased risk of heart valve regurgitation has been added to the product information for these medicines and a letter sent to relevant healthcare professionals in the UK.

About heart valve regurgitation

Heart valve regurgitation, also called heart valve incompetence or insufficiency or leaking valve, occurs when blood flows back through the valves as they are closing or when they should be completely closed.

The risk of heart valve regurgitation is increased in the presence of risk factors such as pre-existing congenital heart valve disease or other risk factors or conditions predisposing for heart valve regurgitation, including connective tissue disorders (for example, Marfan syndrome, Ehlers-Danlos syndrome), hypertension, Turner’s syndrome, Behcet’s disease, rheumatoid arthritis, and infective endocarditis.

Some people with heart valve regurgitation may experience symptoms of heart failure, including:

  • shortness of breath, especially when lying down flat in bed

  • swelling of the ankles, feet, or abdomen

  • new-onset heart palpitations

When initiating systemic or inhaled fluoroquinolone medicines, tell patients of the need to seek immediate medical attention if they develop the above signs and symptoms since they may suggest the presence of heart valve regurgitation.

Report suspected reactions on a Yellow Card

Please continue to report 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 are asked to submit reports using the Yellow Card scheme electronically using:

When reporting please provide as much information as possible, including information about medical history, any concomitant medication, onset, treatment dates, and product brand name.

Article citation: Drug Safety Update volume 14, issue 5: December 2020: 1.

Post-publication note:

Amendments were made to this article in January 2021 to include a link to the letter to healthcare professionals.

  1. Etminan M and others. ‘Oral Fluoroquinolones and Risk of Mitral and Aortic Regurgitation’. Journal of the American College of Cardiology 2019; volume 74, pages 1444–50. ↩

Updates to this page

Published 17 December 2020
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