Drug interactions with quinolones

Numerous drug interactions with the new 4-quinolone antimicrobial agents have now been established. Many, but not all, quinolones are extensively metabolized and can have inhibitory effects on the liver cytochrome P450 enzyme system, leading to reduced metabolism and clearance of certain other drugs that are normally thus eliminated. Examples include the highly significant interaction between enoxacin and theophylline and the interaction between ciprofloxacin and theophylline, which may also be important clinically. The quinolone-caffeine interaction does not usually cause problems. Absorption of all quinolones from the stomach and small intestine is greatly reduced by antacids containing magnesium or aluminium salts, including sucralfate, probably as a result of the formation of nonabsorbable chelates. Cimetidine can reduce the clearance of pefloxacin (but not of ciprofloxacin) through its effects on liver metabolism, although newer H2-inhibitors appear not to have these effects. Probenecid reduces the renal elimination of some quinolones by inhibiting tubular secretion. New evidence is now coming to light of interactions between certain nonsteroid antiinflammatory drugs (e.g., fenbufen), quinolones, and gamma-aminobutyric acid (GABA) receptors, producing increased cerebral excitation and, sometimes, epileptiform convulsions.