Safety and tolerability of fluoroquinolones.

Since their introduction in the mid-1980s, the fluoroquinolones have been administered to more than 100 million patients. Generally, adverse effects reported in association with the fluoroquinolones have been those that could have been predicted by previous experience with non-fluorinated derivatives and by animal toxicity studies. Examples of such adverse events are CNS-related toxicity, upper gastrointestinal tract reactions and phototoxicity. Some adverse experiences in animals, notably cartilage toxicity, have been of minimal clinical importance. This should lead to a re-evaluation of the possible paediatric indications for the fluoroquinolones. With temafloxacin, which was withdrawn from clinical use in June 1992, new and serious adverse events were reported at a frequency of about 1 per 3500 patients treated. This frequency of adverse events is too low to be detected even in very careful analyses of phase III registration studies. Anaphylaxis, haemolytic anaemia and renal failure were the most striking adverse events reported with temafloxacin, and, in addition, hypoglycaemia and hepatic failure were reported. These reactions may be attributable to an immunological reaction in some patients. Because of the rarity of these reactions, they can be detected only by studies encompassing thousands of patients, usually during postmarketing surveillance. Safety monitoring of each new fluoroquinolone during its early clinical use is therefore recommended.