Drugs Xagena
Acorda Therapeutics anf FDA ( Food and Drug Administration ) have informed that concomitant use of Tizanidine ( Zanaflex ) with Fluvoxamine ( Luvox ) or Ciprofloxacin ( Cipro ), potent CYP1A2 inhibitors, is contraindicated.
The interaction between Tizanidine and either Fluvoxamine or Ciprofloxacin, characterized by markedly and potentially dangerously elevated serum Tizanidine levels, is most likely due to inhibition of CYP1A2 by Fluvoxamine or Ciprofloxacin.
Although there have been no clinical studies evaluating the effects of other CYP1A2 inhibitors on Tizanidine, other CYP1A2 inhibitors may lead to substantial increases in Tizanidine blood concentrations. Therefore, concomitant use of tizanidine with other CYP1A2
inhibitors, such as Zileuton ( Zyflo ), other fluoroquinolones, antiarrythmics ( Amiodarone, Mexiletine, Propafenone, and Verapamil), Cimetidine ( Tagamet ), Famotidine ( Pepcid ), oral contraceptives, Acyclovir ( Zovirax ) and Ticlopidine ( Ticlid ) should ordinarily
be avoided.
If their use is clinically necessary, they should be used with caution.
Addition of two contraindications to the Contraindications section
Contraindications
Concomitant use of Tizanidine with Fluvoxamine or with Ciprofloxacin, potent inhibitors of
CYP1A2, is contraindicated. Significant alterations of pharmacokinetic parameters of
Tizanidine including increased AUC, t1/2, Cmax, increased oral bioavailability and decreased
plasma clearance have been observed with concomitant administration of either Fluvoxamine
or Ciprofloxacin. This pharmacokinetic interaction can result in potentially serious adverse
events.
Zanaflex is contraindicated in patients with known hypersensitivity to Tizanidine or its ingredients.
Addition of two Warnings sections
Potential interaction with Fluvoxamine or Ciprofloxacin
In a pharmacokinetic study, Tizanidine serum concentration was significantly increased
( Cmax 12-fold, AUC 33-fold ) when the drug was given concomitantly with Fluvoxamine.
Potentiated hypotensive and sedative effects were observed. Fluvoxamine and Tizanidine
should not be used together.
In a pharmacokinetic study,Tizanidine serum concentration was significantly increased
( Cmax 7-fold, AUC 10-fold ) when the drug was given concomitantly with Ciprofloxacin.
Potentiated hypotensive and sedative effects were observed. Ciprofloxacin and Tizanidine
should not be used together.
Possibile interaction with other CYP1A2 inhibitors
Because of potential drug interactions, concomitant use of Tizanidine with other CYP1A2
inhibitors, such as Zileuton,other fluoroquinolones,antiarrythmics ( Amiodarone, Mexiletine,
Propafenone, and Verapamil ), Cimetidine, Famotidine, oral contraceptives, Acyclovir and
Ticlopidine should ordinarily be avoided.
If their use is clinically necessary, they should be used with caution.
Pharmacokinetics and dosing administration considerations
Food has complex effects on Tizanidine hydrochloride pharmacokinetics. These pharmacokinetic
differences may result in clinically significant differences when switching administration of the
tablet between the fed or fasted state, switching administration of the capsule between the fed or
fasted state, switching between the tablet and capsule in the fed state,or switching between
the intact capsule and sprinkling the contents of the capsule on applesauce. These changes may
result in increased adverse events or delayed/more rapid onset of activity, depending upon the nature of the switch. For this reason, the prescriber should be thoroughly familiar with the changes in kinetics associated with these different conditions.
Source: FDA, 2007
XagenaMedicine_2007
