Overview
11 DESCRIPTION Tizanidine hydrochloride is a central alpha2-adrenergic agonist. Tizanidine hydrochloride is almost a white to slightly yellow crystalline powder. Tizanidine is slightly soluble in water and methanol. Its chemical name is 5-chloro-4-(2- imidazolin-2-ylamino)-2,1,3-benzothiadiazole monohydrochloride. Tizanidine’s molecular formula is C 9 H 8 ClN 5 S-HCl, its molecular weight is 290.
Mechanism of Action
12 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. 12.3 Pharmacokinetics Absorption and Distribution Following oral administration, tizanidine is essentially completely absorbed. The absolute oral bioavailability of tizanidine is approximately 40% (CV = 24%), due to extensive first-pass hepatic metabolism. Tizanidine is extensively distributed throughout the body with a mean steady state volume of distribution of 2.
Indications
- 1 INDICATIONS AND USAGE Tizanidine hydrochloride is indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine hydrochloride should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration ( 2.1 )]. Tizanidine hydrochloride is a central alpha-2-adrenergic agonist indicated for the management of spasticity.
Common Doses
- 2 mg
- 4 mg
- 36 mg
- 16 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended starting dose: 2 mg; dose can be repeated at 6- to 8-hour intervals, up to a maximum of 3 doses in 24 hours ( 2.1 ) Dosage can be increased by 2 mg to 4 mg per dose, with 1 to 4 days between increases; total daily dose should not exceed 36 mg ( 2.1 ) Tizanidine pharmacokinetics differs between tablets and capsules, and when taken with or without food. These differences could result in a change in tolerability and control of symptoms ( 2.1 , 12.
Contraindications
- 4 CONTRAINDICATIONS Tizanidine hydrochloride capsules is contraindicated in patients taking potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin [see Drug Interactions ( 7.1 , 7.2 )]. Concomitant use with potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin( 4 , 5.5 , 7.1 , 7.2 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in other sections of the prescribing information: Hypotension [see Warnings and Precautions ( 5.1 )] Liver Injury [see Warnings and Precautions ( 5.2 )] Sedation [see Warnings and Precautions ( 5.3 )] Hallucinosis/Psychotic-Like Symptoms [see Warnings and Precautions ( 5.4 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.6 )] The most common adverse reactions (greater than 2% of 264 patients taking tizanidine and greater than in placebo-treated patients in three multiple dose, placebo-controlled...
Interactions
- 7 DRUG INTERACTIONS 7.1 Fluvoxamine Concomitant use of fluvoxamine and tizanidine is contraindicated. Changes in pharmacokinetics of tizanidine when administered with fluvoxamine resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [see Contraindications ( 4 ) and Clinical Pharmacology ( 12.3 )]. 7.2 Ciprofloxacin Concomitant use of ciprofloxacin and tizanidine is contraindicated.