Reactions 1006 - 19 Jun 2004

Fluvoxamine significantly alterstizanidine pharmacokinetics

"Fluvoxamine drastically affects the pharmacokineticsand pharmacodynamics of tizanidine", reportresearchers from Finland.

To investigate the effects of fluvoxamine on thepharmacokinetics and pharmacodynamics of tizanidine,the researchers conducted a double-blind randomisedcrossover study in which 10 male volunteers aged21–31 years were randomised to receive fluvoxamine100mg or placebo once daily for 4 days, with an oraldose of tizanidine 4mg on day 4.

Relative to placebo, fluvoxamine markedly increasedtizanidine plasma concentrations, mean AUC∞, Cmax andmean elimination t1/2. Moreover, substantial increases intizanidine Cmax and total AUC were seen in every subjectduring the fluvoxamine phase. The pharmacodynamicresponses to tizanidine were also markedly increased byfluvoxamine. During the fluvoxamine phase, meanvalues of the lowest systolic and diastolic BP were79 ± 10 and 46 ± 5mm Hg, respectively, compared with115 ± 8 and 66 ± 7mm Hg, respectively, during theplacebo phase. In addition, the lowest HR during thefluvoxamine phase, 48 ± 6 beats/min, was significantlyless than that during the placebo phase,52 ± 5 beats/min. Furthermore, during the fluvoxaminephase, all volunteers were somnolent and dizzy for3–6 hours after tizanidine ingestion; these adverseeffects were much milder during the placebo phase.

The researchers say "clinicians should know thatfluvoxamine may dangerously increase theconcentration-dependent adverse effects of tizanidine",and that "their concomitant use must be avoided".Granfors MT, et al. Fluvoxamine drastically increases concentrations and effects oftizanidine: a potentially hazardous interaction. Clinical Pharmacology andTherapeutics 75: 331-341, No. 4, Apr 2004 800978152

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Reactions 19 Jun 2004 No. 10060114-9954/10/1006-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved