Dangerous Interaction Between The Antidepressant Fluvoxamine And The Muscle Relaxant Tizanidine

Researchers from Finland have found that the antidepressant drug fluvoxamine (brand names Fevarin, Faverin, Luvox etc.) drastically increases the concentrations of tizanidine (Sirdalud, Zanaflex) in blood.

Concomitant use of fluvoxamine and tizanidine results in severe and prolonged decrease in blood pressure and greatly enhanced 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. Both fluvoxamine and tizanidine have been in wide clinical use for more than 10 years.

The concentrations of tizanidine in blood were increased on average 33-fold by fluvoxamine in a carefully controlled study in healthy volunteer subjects. The volunteers ingested the usual 100-mg dose of fluvoxamine or placebo daily for 4 days, and then a single 4-mg dose of tizanidine. The interaction was observed in each of the ten subjects; the smallest increase in tizanidine concentration by fluvoxamine was 14-fold, the greatest increase was 103-fold!

The effects of tizanidine were much stronger during fluvoxamine treatment than during placebo treatment. In particular, the decrease in systolic blood pressure, to the level of 80-mm Hg or even less, was an alarming finding. Such grave hypotension is dangerous, eg in elderly subjects and in patients who have heart problems. Also the central nervous system effects of tizanidine were greatly enhanced by fluvoxamine: all ten subjects were somnolent and dizzy for 3 to 6 hours after tizanidine intake.

Both tizanidine and fluvoxamine are widely used drugs in many countries, including USA. In Finland (population 5 200 000) about 10 000 patients are using tizanidine daily, and about 5000 patients are using fluvoxamine daily. Different types of acute and chronic pain syndromes are common in the patients with depression. Therefore, it is likely that fluvoxamine and tizanidine can be coadministrered frequently, if the risk of the interaction is not recognised by clinicians.

The interaction resulted from inhibition of the liver metabolism of tizanidine by fluvoxamine. Further studies are being carried out to characterise the potential interactions of tizanidine with 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 April issue of the scientific journal Clinical Pharmacology & Therapeutics.