Fenbufen Ciprofloxacin

Naora, K. Katagiri, Y. Ichikawa, N. Hayashibara, M. Iwamoto, K. Simultaneous high-performance liquid chromatographic determination of ciprofloxacin, fenbufen and felbinac in rat plasma. J.Chromatogr., 1990, 530, 186—191... 

Co-administration of fenbufen and fluoroquinolones has been associated with seizures (141). The structure at the 7-position greatly affects the risk of NSAID-potentiated nervous system effects. Fluoroquinolones with unsubstituted piperazinyl rings (ciprofloxacin, enox-acin, and norfloxacin) have a strong interaction with NSAIDs (142). The increased risk of seizures is not caused by increased serum concentrations of fluoroquinolones, since their pharmacokinetics are not altered by NSAIDs (143). The mechanism has been suggested to be facilitation by fenbufen of the fluoroquinolone-induced inhibition of GABAa receptor function in the hippocampus and frontal cortex (144). 

A number of cases of convulsions have been seen in Japanese patients given fenbufen with enoxacin, and there is also one possible case involving ofloxacin. Use of these particular drugs together should be avoided. Normally no interaction seems to occur with most quinolones and NSAIDs, except where there is a predisposition to convulsive episodes. Isolated cases of convulsions, other neurological toxicity or skin eruptions have been seen when ciprofloxacin was given with indometacin, mefenamic acid or naproxen. These appear to be very rare events. 

A study in 8 healthy subjects found that the pharmacokinetics of ciprofloxacin were unaffected by treatment with fenbufen for 3 days. Another study found that combined single doses of ciprofloxacin and fenbufen in 12 healthy subjects produced no evidence, using EEG recordings, of increased CNS excitatory effects. ... 

Reports of adverse interactions between other quinolones and NSAIDs are extremely rare. The general warning about convulsions with quinolones and NSAIDs issued by the CSM in the seems to be an extrapolation from the interaction between enoxacin and fenbufen, and from some animal experiments. In addition to the data cited above, an epidemiological study of 856 users of quinolones (ciprofloxacin, enoxacin, nalidixic acid) and a range of NSAIDs found no cases of convulsions. The overall picture would therefore seem to be that although a potential for interaction exists, the risk is very small indeed and normally there would seem to be little reason for most patients taking quinolones to avoid NSAIDs. Epileptic patients are a possible exception (see Antiepileptics H- Quinolones , p.522) and it would seem prudent to avoid quinolones and NSAIDs wherever possible in these patients. 

Kamali F. Lack of a pharmacokinetic interaction between ciprofloxacin and fenbufen. J Clin Pham Ther (1994) 19, 257-9. 

Kamali F, Ashton CH, Marsh VR, Cox J. Is there a pharmacodynamic interaction between ciprofloxacin and fenbufen Br J Clin Phamacol (1997) 43, 545P-546P. 

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