Generalized seizures induced by norfloxacin?/nThe text in the Swedish catalog of approved medicinal

Fråga: Generalized seizures induced by norfloxacin?

The text in the Swedish catalog of approved medicinal products, regarding seizures is different for ciprofloxacin as compared to norfloxacin.

A 62-year-old hypertensive woman treated with Salures-K (potassium chloride + bendroflumethiazide) starts treatment with Lexinor (norfloxacin) 400 mg, one tablet twice daily due to a urinary tract infection. Three days later she arrives at the emergency unit with generalized seizures, grand mal, and fever. Lexinor was withdrawn. Computed tomography and lumbar puncture were without remarks.

Sammanfattning: Convulsions can appear during treatment with norfloxacin as well as ciprofloxacin. The side-effect is dosedependent as well as dependent on the kidney function.

Svar: The fluoroquinolone drug norfloxacin as well as ciprofloxacin are known to cause central nervous system effects. During treatment with norfloxacin effects such as headache, dizziness and paresthesias can be seen in one percent of treated patients (1). These side-effects are more common in elderly patients and patients with decreased kidney function, further, they are dose dependent and disappear after withdrawal of the drug (2). Epileptogenic cramps have also been reported to occur during treatment with fluoroquinolones. The mechanism has been proposed to be an inhibition of GABA at GABA-receptors in CNS (3). Comparative studies regarding the frequency of CNS side-effects between the different fluoroquinolones have not been found in the literature according to an earlier Drugline-document from 1995 (4).

The Swedish Adverse Drug Reactions Advisory Committee (SADRAC) has received 469 reports in connection to the use of norfloxacin of which 98 were reports concerning neurological side-effects. These include convulsions (three cases), epileptic seizures (three cases) and state of cramp (one case). The figures for ciprofloxacin were: 274 reports of which 39 concerned neurological side-effects including convulsions (three cases), epileptic seizures (five cases) and aggravated epilepsy (one case). The sales figures have increased during the last five years for ciprofloxacin compared with those of norfloxacin but they are still lower for ciprofloxacin in comparison.

We recommend that this case be reported to the regional centre of SADRAC. 1 Biverkningar av Lexinor - En treårsuppföljning. Information från Socialstyrelsens Läkemedelsavdelning 1989:4 2 Drugline nr 10494 (year 1994) 3 Karki SD, Bentley DW, Raghavan M: Seizure with ciprofloxacin and theophylline combined therapy. 4 Drugline nr 11345 (year 1995)