ZANAFLEX- tizanidine hydrochloride capsule
ZANAFLEX- tizanidine hydrochloride tablet
Acorda Therapeutics, Inc.
1 INDICATIONS AND USAGE
Zanaflex is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with Zanaflex should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration(2.1) ].
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Information
Zanaflex Capsules� or Zanaflex� tablets may be prescribed with or without food. Once the formulation has been selected and the decision to take with or without food has been made, this regimen should not be altered.
Food has complex effects on tizanidine pharmacokinetics, which differ with the different formulations. Zanaflex Capsules and Zanaflex tablets are bioequivalent to each other under fasting conditions (more than 3 hours after a meal), but not under fed conditions (within 30 minutes of a meal). These pharmacokinetic differences may result in clinically significant differences when switching administration of tablet and capsules and when switching administration between the fed or fasted state. These changes may result in increased adverse events, or delayed or 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 [see Clinical Pharmacology (12.3) ].
The recommended starting dose is 2 mg. Because the effect of Zanaflex peaks at approximately 1 to 2 hours post-dose and dissipates between 3 to 6 hours post-dose, treatment can be repeated at 6 to 8 hour intervals, as needed, to a maximum of three doses in 24 hours.
Dosage can be gradually increased by 2 mg to 4 mg at each dose, with 1 to 4 days between dosage increases, until a satisfactory reduction of muscle tone is achieved. The total daily dose should not exceed 36 mg. Single doses greater than 16 mg have not been studied.
3 DOSAGE FORMS AND STRENGTHS
Capsules
2 mg: Light blue opaque body with a light blue opaque cap with �2 MG" printed on the cap
4 mg: White opaque body with a blue opaque cap with �4 MG" printed on the cap 6 mg: Blue opaque body with a white stripe and blue opaque cap with �6 MG" printed on the cap
Tablets
4 mg white, uncoated tablets with a quadrisecting score on one side and debossed with �A594? on the other side
4 CONTRAINDICATIONS
Zanaflex is contraindicated in patientstaking potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin [see Drug Interactions (7.1, 7.2)].
5 WARNINGS AND PRECAUTIONS
5.1 Hypotension
Tizanidine is an ?2 -adrenergic agonist that can produce hypotension. Syncope has been reported in the post marketing setting. The chance of significant hypotension may possibly be minimized by titration of the dose and by focusing attention on signs and symptoms of hypotension prior to dose advancement. In addition, patients moving from a supine to fixed upright position may be at increased risk for hypotension and orthostatic effects.
DESCRIPTION
Zanaflex� (tizanidine hydrochloride) is a central alpha2 -adrenergic agonist. Tizanidine HCl is a white to off-white, fine crystalline powder, which is odorless or with a faint characteristic odor. Tizanidine is slightly soluble in water and methanol; solubility in water decreases as the pH increases. Its chemical name is 5-chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiadiazole monohydrochloride. Tizanidine�s molecular formula is C9 H8 ClN5 S-HCl, its molecular weight is 290.2
CLINICAL PHARMACOLOGY
12.1 Mechanism of action
Tizanidine is a central alpha-2-adrenergic receptor agonist and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. The effects of tizanidine are greatest on polysynaptic pathways. The overall effect of these actions is thought to reduce facilitation of spinal motor neurons
