Fluoroquinolones are generally well-tolerated antimicrobials with adverse events mostly affecting the gastrointestinal tract, skin and CNS. Following gastrointestinal events at number one, CNS adverse events associated with fluoroquinolones are the second most common adverse event with an overall incidence from a low of 0.2% for levofloxacin to 5.4% for moxifloxacin. Symptoms can include headache, dizziness, sleep disorders, psychosis and delirium. Convulsions have also been reported, usually occurring in the presence of predisposing factors such as concomitant theophylline or NSAID usage.

Fluoroquinolone associated CNS toxicity appears to be related to inhibition of GABA binding to the GABAA receptors, resulting in CNS stimulation. The degree of GABA binding is related to the substituent attached to the R7 position of the quinolone nucleus. This binding is enhanced by NSAIDs. As shown, levofloxacin is the least likely to cause epileptogenic activity in animal studies.

Skin adverse events associated with fluoroquinolone use have been reported, with the major effect being photosensitivity. These occur in 0.2-5.1% of fluoroquinolone-treated patients, with sparfloxacin more likely to cause these, followed by grepafloxacin and moxifloxacin. Levofloxacin has a very low incidence of skin adverse events at 0.2%.

Fluoroquinolone associated liver toxicity occurs in 2-3% of patients taking fluoroquinolones, with the most common indication being an increase in serum transaminases and alkaline phosphatase. There is a very low frequency of abnormal liver function tests associated with levofloxacin administration, none of which have necessitated discontinuation of therapy.

Arthropathy is thought to be a class effect, with tendinitis and tendon rupture also reported. This is more likely to develop in males, and those taking steroids or having renal disease. Specific agents reported to be associated with tendinitis include norfloxacin, ciprofloxacin, pefloxacin, enoxacin, and sparfloxacin. In contrast, there has only been one case of possible levofloxacin-related tendinitis during preclinical development, and tendon rupture has not been reported.

Among the fluoroquinolones, the greatest database has been built up for levofloxacin, with more than 200 million prescriptions worldwide for this agent. The overall incidence of adverse events associated with fluoroquinolones highlights the fact that levofloxacin has an extremely low incidence of CNS episodes, liver effects and also has the lowest phototoxic potential among the fluoroquinolones. This excellent safety profile of levofloxacin has also been reported for patients taking long-term therapy. Therefore, levofloxacin can be prescribed by the physician with confidence in its excellent safety record.