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The United Kingdom: Fluoroquinolone antibiotics: new restrictions and precautions for use due to very rare reports of disabling and potentially long-lasting or irreversible side effects
 
Medicines and Healthcare products Regulatory Agency (MHRA) announces that disabling, long-lasting or potentially irreversible adverse reactions affecting musculoskeletal and nervous systems have been reported very rarely with fluoroquinolone antibiotics.

An 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 Jun 2018.

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 European Medicines Agency’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.

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.

Healthcare professionals are advised:
- 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.
- 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) unless other antibiotics that are commonly recommended for these infections are considered inappropriate
- Ciprofloxacin or levofloxacin should no longer be prescribed for uncomplicated cystitis unless other antibiotics that are commonly recommended are considered inappropriate.
- 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.

Please refer to the following website in MHRA for details: http://www.gov.uk/drug-safety-update/fluoroquinolone-antibiotics-new-restrictions-and-precautions-for-use-due-to-very-rare-reports-of-disabling-and-potentially-long-lasting-or-irreversible-side-effects

In Hong Kong, there are 186 registered pharmaceutical products for systemic administration containing fluoroquinolones and quinolones, including ciprofloxacin (82 products), levofloxacin (59 products), moxifloxacin (6 products), norfloxacin (7 products), ofloxacin (29 products), prulifloxacin (1 product), nalidixic acid (1 product) and pipemidic acid (1 product). All products are prescription-only medicines. So far, the Department of Health (DH) has received 4 cases of adverse drug reaction related to levofloxacin (of which one case is related to tendinitis and neuropathy), and 1 case related to moxifloxacin. The DH has not received any case of adverse drug reaction related to other fluoroquinolones and quinolones.

Drug safety news related to fluoroquinolones was previously issued by various overseas drug regulatory authorities, and posted on the Drug Office website since 8 Nov 2011, with the last update posted on 17 Nov 2018. Letters to inform local healthcare professionals of the above safety news were issued in 2011, 2013, 2016 and 2018. In 2013, the Registration Committee of the Pharmacy and Poisons Board (the Registration Committee) discussed the safety of fluoroquinolones with peripheral neuropathy, and decided that the relevant warnings should be included in the sales packs and/or package inserts of the products. In 2016, the Registration Committee discussed the safety of fluoroquinolones with disabling and potentially permanent side effects of the tendons, muscles, joints, nerves, and central nervous system, and subsequently decided to remain vigilant on further updates by other overseas drug regulatory authorities.

As previously reported, the matter will be further discussed by the Registration Committee. The DH will remain vigilant on safety update of the drugs issued by other overseas drug regulatory authorities.

Ends/Friday, Mar 22, 2019
Issued at HKT 16:00
 
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