ciprofloxacin - restrictions and precautions due to very rare reports of disabling and potentially long-lasting or irreversible side effects

Last edited 09/2023 and last reviewed 09/2023

Fluoroquinolone antibiotics - restrictions and precautions for use due to very rare reports of disabling and potentially long-lasting or irreversible side effects

Disabling, long-lasting or potentially irreversible adverse reactions affecting musculoskeletal and nervous systems have been reported very rarely with fluoroquinolone antibiotics

• fuoroquinolone treatment should be discontinued at the first signs of a serious adverse reaction, including tendon pain or inflammation
  
  
• Advice for healthcare professionals (1):
  
  
• 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

Updated 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)
  
  
• 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 (1)
  
  
• 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.

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.

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.

A study showed no increased risk of aortic aneurysm and aortic dissection (AA/AD) associated with fluoroquinolone (FQ) use (3).

Reference:

• MHRA - Fluoroquinolone antibiotics: new restrictions and precautions for use due to very rare reports of disabling and potentially long-lasting or irreversible side effects .Drug Safety Update volume 12, issue 8: March 2019: 1.
• Drug Safety Update volume 17, issue 1: August 2023: 1.
• Hung K et al. Lack of association between fluoroquinolone and aortic aneurysm or dissection, European Heart Journal, 2023;, ehad627, https://doi.org/10.1093/eurheartj/ehad627