Antiepileptics with NSAIDs

QUINOLONES NS AIDs Reports of convulsions when NSAIDs were added to quinolones in those with epilepsy Unknown Care in co-administering antiepileptics and NSAIDs in patients with epilepsy... 

SJS was for many years considered a severe variant of erythema multiforme major (EMM) however, over the past decade some experts have reclassified SJS as a less severe variant of toxic epidermal necrolysis (TEN) rather than a form of EMM. However, this perspective is not universally accepted. SJS occurs acutely in all ages, with 20% in children and a peak incidence in adults between the second and fourth decades of life. SJS is a potentially fatal disorder with a mortality of approximately 5%.TEN has a mortality rate of approximately 30%. About 50% of cases of these disorders are idiopathic. Identifiable causal factors include microbial infection, particularly with Mycoplasma pneumoniae and HS Vj and medications, including sulfonamides, tetracycline, penicillin, nonsteroidal anti-inflammatory drugs (NSAIDs), psychotropic agents, antiepileptics, and immunizing vaccines. Recent research suggests that HSV infection is a principal fector in the genesis of EMM, whereas medications are a more likely precipitant of SJS and TEN. 

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. 

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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