TIZANIDINE SUMMARY
Tizanidine hydrochloride is a centrally acting α2-adrenergic agonist. Tizanidine HCl (tizanidine) is a white to off-white, fine crystalline powder, 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-benzothiodiazole hydrochloride.
Tizanidine (tizanidine) is indicated for the following:
Tizanidine is a short-acting drug for the management of spasticity. Because of the short duration of effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important (see DOSAGE AND ADMINISTRATION).
|
NEWS HIGHLIGHTS
Published Studies Related to Tizanidine
Botulinum neurotoxin versus tizanidine in upper limb spasticity: a placebo-controlled study. [2009.04]
BACKGROUND: While spasticity is commonly treated with oral agents or botulinum neurotoxin (BoNT) injection, these treatments have not been systematically compared... CONCLUSIONS: BoNT is safer and more effective than TZD in reducing tone and disfigurement in upper-extremity spasticity, and may be considered as first-line therapy for this disorder.
Botulinum Neurotoxin vs Tizanidine in Upper Limb Spasticity: A Placebo-Controlled Study. [2008.10.31]
BACKGROUND: While spasticity is commonly treated with oral agents or botulinum neurotoxin (BoNT) injection, these treatments have not been systematically compared... CONCLUSIONS: BoNT is safer and more effective than TZD in reducing tone and disfigurement in upper extremity spasticity, and may be considered as first line therapy for this disorder.
Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam--probes of CYP2C9, CYP1A2, and CYP3A4. [2007.06]
Case reports suggest that cranberry juice can increase the anticoagulant effect of warfarin. We investigated the effects of cranberry juice on R-S-warfarin, tizanidine, and midazolam; probes of CYP2C9, CYP1A2, and CYP3A4.A pharmacokinetic mechanism for the cranberry juice-warfarin interaction seems unlikely.
Effects of food on the single-dose pharmacokinetics/pharmacodynamics of tizanidine capsules and tablets in healthy volunteers. [2006.09]
BACKGROUND: A multiparticulate capsule formulation of the alpha2-adrenergic agonist tizanidine has been developed to decrease C(max), AUC, and associated somnolence, while maintaining efficacy. OBJECTIVE: The purpose of this study was to compare the pharmacokinetics and impact of somnolence on cognitive function after single doses of the tablet and capsule formulations of tizanidine under fed and fasted conditions in healthy volunteers... CONCLUSIONS: The results of this study in healthy volunteers suggest that the capsule and tablet formulations of tizanidine were bioequivalent only in the fasted state. The capsule formulation exhibited a food effect that reduced C(max) and AUC(0-t), and significantly increased T(max), which was associated with a delay in cognitive impairment. The large interpatient variability in plasma profiles most likely dampened the ability to fully elucidate the differences between the 2 formulations.
Rifampicin is only a weak inducer of CYP1A2-mediated presystemic and systemic metabolism: studies with tizanidine and caffeine. [2006.06]
OBJECTIVE: Rifampicin greatly reduces the plasma concentrations of many drugs. Our aim was to characterise the inducibility of cytochrome P450 (CYP) 1A2 by rifampicin, using tizanidine and caffeine as probe drugs for presystemic and systemic CYP1A2-mediated metabolism... CONCLUSIONS: Rifampicin moderately decreases the plasma concentrations of tizanidine. The strong inducing effects of rifampicin on other CYP enzymes, e.g. CYP3A4, may have contributed to the findings, and the inducibility of CYP1A2-mediated presystemic (tizanidine) and systemic (tizanidine, caffeine) metabolism by rifampicin is weak at the most. Compared to CYP3A4 substrate drugs, substrates of CYP1A2 are much less susceptible to drug interactions caused by enzyme inducers of the rifampicin type.
Clinical Trials Related to Tizanidine
Comparison of Safety and Efficacy of Tizanidine Hydrochloride Capsules Versus Zanaflex® (Tizanidine Hydrochloride Tablets) Taken While in the Fed State (Just After a Meal) and in the Fasted State (Before a Meal) in Patients With Moderate to Severe Spasticity. [Completed]
This study is being conducted to compare the impact of somnolence (sleepiness) on cognition
(awareness) as well as the safety and effectiveness of tizanidine hydrochloride capsules
versus Zanaflex® (tizanidine hydrochloride tablets) taken while in the fed state (just after
a meal) and in the fasted state (before a meal) in patients with moderate to severe
spasticity.
Study of Nighttime Dosing of Sublingual Tizanidine (12 mg) in Multiple Sclerosis (MS) Patients With Significant Spasticity [Completed]
Nightly administration of 8 mg of a unique sublingual (under the tongue) formulation of
tizanidine, a known anti-spasticity medication, has been shown in a previous study to improve
next-day spasticity, about 12 hours following dosing in 20 multiple sclerosis (MS) patients.
This improvement was statistically significant when compared to oral tizanidine dosing. The
current study is being undertaken to see if increasing the dose to 12 mg once nightly will
result in an even greater improvement, with a longer effect, i. e., next day improvement in
spasticity both in the morning as well as in the late afternoon.
Pilot, Proof-of-Concept Study of Sublingual Tizanidine in Children With Chronic Traumatic Brain Injury (TBI) [Completed]
Nightly administration of a unique, sublingual (under the tongue) formulation of tizanidine,
a known anti-spasticity medication, has been shown in a previous study to improve sleep and
next-day functioning in CP (cerebral palsy) patients. It is hypothesized that this
improvement in sleep efficiency (i. e.,fewer wake episodes, longer time asleep, etc.) with
resulting improvement in quality-of-life (i. e.,improvements in next-day functioning,
cognition and movement) may also be seen in a similar patient population, i. e., children with
traumatic brain injury (TBI).
BOTOX® Versus Zanaflex® for the Treatment of Post-Stroke or Traumatic Brain Injury Upper Limb Spasticity [Completed]
In this study, we will compare BOTOX® versus Zanaflex ® for the treatment of muscle
overactivity in the upper limb following stroke or brain traums. This is a critical step in
the development of local intramuscular treatment for patients with muscle overactivity
following an acute brain lesions, as opposed to the more classic oral treatments.
This study will be a multicenter, randomized, prospective, parallel, double blind study that
enrolls subjects at twelve sites (including Mt. Sinai) throughout the United States and
Europe. The purpose of this study is to evaluate the safety and efficacy of BOTOX® compared
to Zanaflex® in reducing upper limb muscle tone in post-stroke subjects, as well as
evaluating changes in muscle tone-related disability and drug-therapy tolerance. This will
be an 18 week study. Subjects are eligible if they have been medically stable with upper
limb spasticity 6 months after their first stroke. Subjects will be randomized to one of
three treatment groups: Treatment Group I - intramuscular BOTOX® plus oral placebo, Treatment Group II - intramuscular placebo plus oral Zanaflex®, Treatment Group III -
intramuscular placebo plus oral placebo. The dose of BOTOX® will be at the discretion of
the investigator with a maximum of 500 U per subject. The dose of the Zanaflex® will be
4mg/day to a maximum of 36mg/day. The study anticipates that 150 subjects will be enrolled
to provide sufficient information to answer the primary objective of safety and efficacy of
the study.
One Year Extension Study To Protocol C2/5/TZ:MS-05 [Not yet recruiting]
Open label, one year extension study to evaluate the clinical efficacy and safety of 12 mg
sublingual tizanidine administered once nightly in MS patients who successfully completed
Phase I/II protocol C2/5/TZ: MS-05 at the Tel Aviv Sourasky Medical Center, Department of
Neurology, Dr. Arnon Karni, PI.
|
|
|
|
Page last updated: 2009-10-20
|
