Quinolone Antibiotics - Adverse Effects

Adverse Effects

In general, fluoroquinolones are well tolerated, with most side effects being mild to moderate. On occasion, serious adverse effects occur. Some of the serious adverse effects that occur more commonly with fluoroquinolones than with other antibiotic drug classes include central nervous system (CNS) and tendon toxicity. The currently marketed quinolones have safety profiles similar to those of other antimicrobial classes. Fluoroquinolones are sometimes associated with an QTc interval prolongation and cardiac arrhythmias, convulsions, tendon rupture, torsade de pointes and hypoglycemia.

These adverse reactions are a class effect of all quinolones; however, certain quinolones are more strongly associated with increased toxicity to certain organs. For example, moxifloxacin carries a higher risk of QTc prolongation, and gatifloxacin has been most frequently linked to disturbed blood sugar levels, although all quinolones carry these risks. Some quinolones were withdrawn from the market because of these adverse events (for example, sparfloxacin was associated with phototoxicity and QTc prolongation; thrombocytopenia and nephritis were seen with tosufloxacin; and hepatotoxicity with trovafloxacin). Simultaneous use of corticosteroids is present in almost one-third of quinolone-associated tendon rupture. The risk of adverse events is further increased if the dosage is not properly adjusted, for example if there is renal insufficiency.

The serious events may occur during therapeutic use at therapeutic dose levels or with acute overdose. At therapeutic doses, they include: CNS toxicity, cardiovascular toxicity, tendon / articular toxicity, and, rarely, hepatic toxicity. Caution is required in patients with liver disease. Events that may occur in acute overdose are rare, and include renal failure and seizure. Susceptible groups of patients, such as children and the elderly, are at greater risk of adverse reactions during therapeutic use. Tendon damage may manifest during, as well as after fluoroquinolone therapy has been completed.

Fluoroquinolones, clindamycin, and fourth generation cephalosporins are considered high-risk antibiotics for the development of Clostridium difficile and MRSA infections. A previously rare strain of C. difficile that produces a more severe disease with increased levels of toxins is becoming epidemic, and may be connected to the use of fluoroquinolones. The European Center for Disease Prevention and Control recommends fluoroquinolones and the antibiotic clindamycin should be minimized in clinical practice due to their high association with C. difficile, a potentially life-threatening super-infection.

The CNS is an important target for fluoroquinolone-mediated neurotoxicity. Spontaneous adverse event reporting in Italy by doctors showed fluoroquinolones among the top three prescribed drugs reported for causing adverse neurological and psychiatric effects. These neuropsychiatric effects included tremor, confusion, anxiety, insomnia, agitation, and, in severe cases, psychosis. Moxifloxacin came out worst among the quinolones for causing CNS toxicity. Some support and patient advocacy groups refer to these adverse events as "fluoroquinolone toxicity". Some people from these groups claim to have suffered serious long-term harm to their health from using fluoroquinolones. A class-action lawsuit has been filed on behalf of individuals alleging harm by the use of fluoroquinolones, as well as action by the consumer advocate group, Public Citizen. Partly as a result of the efforts of Public Citizen, the FDA ordered black box warnings on all fluoroquinolones, advising consumers of an enhanced risk of tendon damage.

The risk of fluoroquinolone-induced tendon injury is elevated in juveniles, and thus the approved uses of fluoroquinolones in persons less that 18 years of age are limited to the use of ciprofloxacin to treat certain types of complicated urinary tract infections and inhalation anthrax. The increased risk of adverse events in juveniles conferred by ciprofloxacin compared to non-fluoroquinolone antibiotics has been demonstrated in controlled clinical trials, and is supported by an internal FDA review of spontaneous adverse event reports.