Advice for healthcare professionals: systemic (by mouth, injection, or inhalation) fluoroquinolones can very rarely cause long-lasting (up to months or years), disabling, and potentially irreversible side effects, sometimes affecting multiple systems, organ classes, and senses

advise patients to stop treatment at the first signs of a serious adverse reaction, such as tendinitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects, and to contact their doctor immediately for further advice – sheet for patients

do not prescribe fluoroquinolones: for non-severe or self-limiting infections, or non-bacterial conditions for some mild to moderate infections (such as in acute exacerbation of chronic bronchitis and chronic obstructive pulmonary disease; please refer to revised indications in the Summary of Product Characteristics) unless other antibiotics that are commonly recommended for these infections are considered inappropriate (see below)

ciprofloxacin or levofloxacin should no longer be prescribed for uncomplicated cystitis unless other antibiotics that are commonly recommended are considered inappropriate (see below)

avoid use in patients who have previously had serious adverse reactions with a quinolone or fluoroquinolone antibiotic

prescribe with special caution for people older than 60 years and for those with renal impairment or solid-organ transplants because they are at a higher risk of tendon injury

avoid use of a corticosteroid with a fluoroquinolone since coadministration could exacerbate fluoroquinolone-induced tendinitis and tendon rupture

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)

New restricted indications

Fluoroquinolones are antibiotics authorised for serious, life-threatening bacterial infections. As for all antibiotic medicines, consideration should be given to official guidance on the appropriate use of antibacterial agents (see section below on Prescribing guidance).

Following an EU-wide review of safety, new restricted indications are being introduced for fluoroquinolone antibiotics available in the UK. Please refer to the updated Summary of Product Characteristics before prescribing:

Ciprofloxacin (Ciproxin)

Levofloxacin

Moxifloxacin (Avelox)

Ofloxacin (Tarivid)

Summaries of Product Characteristics will be updated in the coming weeks. In the meantime, see EMA document for exact changes made in indications.

The quinolone nalidixic acid was authorised for urinary tract infections, which is no longer a permitted indication. Therefore, the licence for nalidixic acid has been cancelled.

Fluoroquinolones should not be prescribed for treatment of mild to moderate infections (such as in acute exacerbation of chronic bronchitis and chronic obstructive pulmonary disease) unless other antibiotics that are commonly recommended for these infections are considered inappropriate.

Relevant situations in which other antibiotics may be understood to be inappropriate are those in which there is resistance to the other first-line antibiotics recommended for these infections; when other first-line antibiotics cause side effects that lead to treatment being stopped or the other first-line antibiotics are contraindicated in an individual; or because first-line antibiotics have failed.

Review of disabling and potentially long-lasting, irreversible side effects

The EU review into the benefits and risks of fluoroquinolone and quinolone antibiotics was triggered by reports of disabling and potentially long-lasting, irreversible side effects mainly affecting the musculoskeletal and nervous systems. The review incorporated the views of patients, healthcare professionals, and academics presented at a public hearing in June 2018.

Details and frequency of cases reported

The review identified data for long-lasting adverse reactions associated with quinolone and fluoroquinolone use from spontaneous reports, the scientific literature and non-clinical mechanistic studies. A review of the EMA’s EudraVigilance database identified 286 cases of serious adverse reactions reported as disabling and lasting for 30 days or more, without any alternative explanations, from across the EU over a 21-year period. Although cumulative fluoroquinolone patient exposure data are not available for this time period, it is estimated that more than 300 million daily doses of fluoroquinolone antibiotics are dispensed every year in the EU.

Although relatively few cases of these disabling and potentially irreversible adverse reactions have been reported, under-reporting is likely. Due to the seriousness of these reactions sometimes reported in previously healthy people, any decision to prescribe a fluoroquinolone should be taken after a careful assessment of the benefits and risks in each case.

Characteristics of adverse reactions reported and recommendation if tendonitis occurs

Serious side effects reported include tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impaired hearing, vision, taste, and smell. In the musculoskeletal system, tendonitis and tendon rupture were most commonly reported, and in the nervous system paraesthesia was most commonly reported.

Tendon damage (especially to the Achilles tendon but also other tendons) 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.

At the first sign of tendinitis (eg, painful swelling, inflammation), treatment with the fluoroquinolone should be discontinued and alternative treatment should be considered. The affected limb or limbs should be appropriately treated (eg, immobilisation). Corticosteroids should not be used if signs of tendinopathy occur.

We have produced a patient sheet to help healthcare professionals to discuss the new measures and actions patients should take.

Precautions for prescribing fluoroquinolones, including for patients at increased risk

Patients who are older than 60 years, have renal impairment, or have had solid-organ transplantation, and those being treated with a corticosteroid are at higher risk of tendon damage. Concomitant treatment with a fluoroquinolone and a corticosteroid should be avoided as the risk of fluoroquinolone-induced tendinitis and tendon rupture may be exacerbated.

Prescribing guidance

Consideration should be given to official guidance on the appropriate use of antibacterial agents. Prescribers should consult NICE and Public Health England’s guidance for managing common infections, including upper and lower respiratory, and urinary tract infections. In Scotland, SIGN have also produced antibiotic guidance for prescribers.

The new EU restrictions closely align with existing UK national guidance. The restrictions should not prevent use of a fluoroquinolone for serious or severe infections if this is consistent with UK national guidance or where there are microbiological grounds, and where the benefit is thought to outweigh the risk.

Report suspected adverse drug reactions via the Yellow Card scheme

As for all medicines, MHRA will continue to monitor the benefit–risk of fluoroquinolone antibiotics. Please continue to report any suspected adverse drug reaction associated with a fluoroquinolone 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.

Further information

EMA’s final recommendation on quinolone- and fluoroquinolone-containing medicinal products.

Article citation: Drug Safety Update volume 12, issue 8: March 2019: 1.