Fenbufen Enoxacin

Many cases of epileptic seizures have been reported in Japan in patients taking a combination of fenbufen and enoxacin (SEDA-12, 85) (SEDA-15,100). 

Morita H, Maemura K, Sakai Y, Kaneda Y. [A case of convulsion, loss of consciousness and subsequent acute renal failure caused by enoxacin and fenbufen.] Nippon Naika Gakkai Zasshi 1988 77(5) 744-5. 

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 total of 17 Japanese patients have been identified, with apparently no previous history of seizures, who in the 1986 to 1987 period developed convulsions when given fenbufen 400 mg to 1.2 g daily with enoxacin 200 to 800 mg. Two case reports of this interaction have been published. An 87-year-old Japanese woman taking enoxacin 200 mg also had convulsions after receiving a single 50-mg intravenous dose of flurbiprofen. ... 

Not fully understood. Convulsions have occurred in a few patients taking quinolones alone, some of whom were epileptics and some of whom were not (see Antiepileptics + Quinolones , p.522). Experiments in mice have shown that quinolones competitively inhibit the binding of gamma-amino butyric acid (GABA) to its receptors. GABA is an inhibitory transmitter in the CNS, which is believed to be involved in the control of convulsive activity. Enoxacin and fenbufen are known to affect the GABA receptor site in the hippocampus and frontal cortex of mice, which is associated with convulsive activity.It could be that, if and when an interaction occurs, the NSAID simply lowers the amount of quinolone needed to precipitate convulsions in already susceptible individuals. 

The interaction between enoxacin and fenbufen is established, but it seems to be uncommon. Nevertheless, it would seem prudent to avoid fenbufen with enoxacin. There are very many alternatives. 

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. 

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See also in sourсe #XX -- [ ]

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