Drug interactions with quinolones

Abstract

The pharmacodynamic and pharmacokinetic drug interactions and pharmaceutical compatibilities of fluoroquinolones are reviewed. Incompatibilities are observed between quinolones and penicillins such as flucloxacillin and amoxicillin and with clindamycin when mixed in an administration set. Fluoroquinolones, especially enoxacin, and to a lesser extent ciprofloxacin and pefloxacin, inhibit the metabolic clearance of theophylline and caffeine. It is advisable to use non-interacting quinolones such as ofloxacin or norfloxacin or to measure theophylline levels and reduce caffeine intake where appropriate. A potential interaction with midazolam needs further study. The absorption of fluoroquinolones is markedly reduced by antacids, calcium carbonate, ferrous sulphate and sucralfate. Although quantitative differences between fluoroquinolones exist, these combinations should be avoided whenever possible. Cimetidine reduces the metabolic clearance of pefloxacin. More studies are needed on the possible reduction of absorption of fluoroquinolones by opiates. Several case reports of a pharmacodynamic interaction between fluoroquinolones and cyclosporin or oral anticoagulants exist. No pharmacokinetic interaction has been observed and more, controlled studies are needed to assess the significance of the pharmacodynamic interaction. A high incidence of convulsions has been observed in patients receiving the combination enoxacin and fenbufen, an NSAID. A synergistic inhibitory effect of fluoroquinolones and several NSAIDs has been observed on the binding of the neurotransmitter GABA. Although the relevance of this interaction is probably not great, except with fenbufen, a possible epileptogenic effect of the combination cannot be excluded.