Dangerous interaction between the antibiotic ciprofloxacin and the muscle relaxant tizanidine

Researchers from Finland have found that the antibiotic ciprofloxacin (brand names Ciproxin, Ciprofloxacin etc.) greatly increases the concentrations of tizanidine (Sirdalud, Zanaflex) in blood. Concomitant use of ciprofloxacin and tizanidine results in severe and prolonged decrease in blood pressure and greatly enhances central nervous system effects.

This previously unrecognised interaction can be dangerous, particularly in elderly patients, and the concomitant use of the two agents must be avoided. Tizanidine is widely used for treatment of musculoskeletal pain associated with increased muscle tension or chronic spasticity.

The concentrations of tizanidine in blood were increased on average 10-fold by ciprofloxacin in a carefully controlled study in healthy volunteer subjects. The volunteers ingested the usual 500-mg dose of ciprofloxacin (or placebo) twice daily for 3 days, and then a single 4-mg dose of tizanidine. The interaction was observed in each of the ten subjects; the greatest increase in tizanidine concentration by ciprofloxacin was 24-fold.

Ciprofloxacin enhanced greatly also the effects of tizanidine. In particular, the decrease in systolic (“upper”) blood pressure, to the level of 90-mm Hg or even less, was an alarming finding. Such hypotension can be dangerous, eg in elderly subjects and in patients who have heart problems. Also the central nervous system effects of tizanidine were greatly enhanced by ciprofloxacin: all ten subjects were somnolent and dizzy for about 3 hours after tizanidine intake.

Both tizanidine and ciprofloxacin are widely used drugs in many countries. E.g. in Finland (population 5 200 000) about 136 000 patients used tizanidine and about 60 000 patients used ciprofloxacin during the year 2003. Therefore, it is likely that ciprofloxacin and tizanidine can be coadministrered, if the risk of the interaction is not recognised by clinicians.

The interaction results from inhibition of the liver metabolism of tizanidine by ciprofloxacin. The same mechanism causes a serious interaction also between the antidepressant fluvoxamine and tizanidine, which was uncovered earlier this year. Further studies are being carried out to study whether there are other unrecognised interactions between tizanidine and other drugs.

The study was conducted at the Department of Clinical Pharmacology, University of Helsinki, by an independent group of researchers led by Professor Pertti J Neuvonen, MD, PhD, and Dr. Janne T Backman, MD, PhD. The study was published in the December issue of Clinical Pharmacology & Therapeutics, the leading scientific journal within the clinical pharmacology and therapeutics area.