04/12/2007

The FDA and Acorda Therapuetics issued an alert concerning increases in tizanidine serum levels when concomitantly used with the potent CYP1A2 inhibitors fluvoxamine or ciprofloxacin. A pharmacokinetic study showed fluvoxamine plus tizanidine causes a 33 fold increase in the area under the curve (AUC) and ciprofloxacin plus tizanidine causes a 10 fold increase in AUC. This interaction greatly increases the risk of tizanidine adverse effects such as sedation and hypotension.

Clinical studies evaluating interactions of other CYP1A2 inhibitors and tizanidine have not been conducted. However, due to these interactions, avoid concomitant use of tizanidine and other CYP1A2 inhibitors (eg zileuton, other fluoroquinolones, antiarrhythmics).

• MedWatch Alert
  http://www.fda.gov/medwatch/safety/2007/safety07.htm#Zanaflex
   
• Letter from Acorda Therapeutics
  http://www.fda.gov/medwatch/safety/2007/Zanaflex_DHCP_3-27-2007.pdf