Management of spasticity associated with cerebral or spinal injury, alone or in conjunction with other standard therapies (e.g., baclofen).
Dosage and Administration
General
Individualize dosage according to the patient’s requirements and response using the lowest dosage that produces optimum response without adverse effects.
Administration
Oral Administration
Clinically important differences (e.g., increased adverse effects, delayed or more rapid onset of activity) may be apparent when switching administration of capsules or tablets between fed and/or fasting states, switching between capsules and tablets in fed state, or switching between administration of intact capsule and sprinkling capsule contents on applesauce. Be thoroughly familiar with possible pharmacokinetic changes associated with these conditions. (See Absorption under Pharmacokinetics.)
Initially, 4 mg; single doses <8 mg not effective in clinical trials, but 4-mg dose used to minimize the incidence of common dose-related adverse effects (e.g., orthostatic hypotension).
Repeat 4-mg dose every 6–8 hours as needed for a maximum of 3 doses in 24 hours.
Increase dosage gradually in increments of 2–4 mg daily over a period of 2–4 weeks until optimum therapeutic effects are obtained with tolerable adverse effects.
Prescribing Limits
Adults
Spasticity
Oral
Maximum 36 mg in a 24-hour period.
Special Populations
Renal Impairment
Initiate with caution in patients with renal impairment (Clcr <25 mL/minute). In these patients, use smaller individual doses during dosage titration; if higher doses are needed, increase the amount of each individual dose rather than increasing the frequency of dosing.
Cautions
Contraindications
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Concomitant therapy with fluvoxamine. (See Specific Drugs under Interactions.)
Known hypersensitivity to tizanidine or any ingredient in the formulation.
Warnings/Precautions
Warnings
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Cardiovascular Effects
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Minimize risk of marked hypotension by careful dosage titration; observe patients for manifestations of hypotension prior to dosage adjustment. Use caution in patients receiving concomitant antihypertensive therapy. (See Interactions.)
Hepatic Effects
Elevations (i.e., >3 times ULN, or 2 times ULN if baseline levels were elevated) of ALT or AST. In patients with elevated aminotransferase concentrations, nausea, vomiting, anorexia, and jaundice occasionally have been reported.
Monitor serum aminotransferase concentrations prior to and during the first 6 months of treatment (e.g., at baseline and at 1, 3, and 6 months) and periodically thereafter.
CNS Effects
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Dose-related somnolence, sometimes severe.
Potential hallucinations generally occurring within the first 6 weeks of therapy. Psychoses associated with hallucinations reported in at least one patient.
General Precautions
Cardiovascular Effects
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Potential for prolongation of the QT interval and bradycardia based on animal studies.
Pulse rate reduction in association with decreases in blood pressure has been reported.
Ocular Effects
Dose-related retinal degeneration and corneal opacities in animal studies.
Discontinuance of Therapy
Possible rebound manifestations with abrupt withdrawal of therapy, including hypertension, tachycardia, hypertonia, tremor, and anxiety.
If therapy is to be discontinued, decrease dosage gradually, particularly in patients who have been receiving high dosages for prolonged periods, to minimize the risk of withdrawal and rebound symptoms.
Specific Populations
Pregnancy
Category C.
Lactation
Not known whether tizanidine is distributed into milk. However, because it is lipid-soluble, tizanidine might be expected to pass into milk. Use caution in nursing women.
Pediatric Use
Safety and efficacy not established.
Geriatric Use
Clearance is decreased 4-fold; use with caution.
Hepatic Impairment
Use only with extreme caution in patients with impaired hepatic function. (See Hepatic Effects under Cautions.)
Renal Impairment
Clearance is reduced by >50% in patients with a Clcr <25 mL/minute. Use caution in patients with renal impairment. (See Renal Impairment under Dosage and Administration.)
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Tizandine and major metabolites are not likely to affect the metabolism of other drugs metabolized by CYP enzymes.
Potential decreased plasma clearance of tizanidine
Use with caution
Use smaller individual doses during dosage titration. If higher doses are needed, increase the amount of each individual dose rather than increasing the frequency of dosing
Rofecoxib (no longer commercially available in the US)
Potential adverse CNS and cardiovascular effects
Pharmacokinetics
Absorption
Bioavailability
Completely absorbed following oral administration of capsules and tablets; peak plasma concentrations attained in about 1 hour.
Commercially available capsules and tablets are bioequivalent under fasting conditions, but not under nonfasting conditions.
Food
Tablets: Food increases the mean peak plasma concentration by about 30%, increases the median time to peak plasma concentration from about 60 minutes to 85 minutes, and increases the extent of absorption by about 30%.
Capsules: Food decreases the mean peak plasma concentration by 20% and increases the median time to peak plasma concentration from about 1 hour to 3 hours, and increases the extent of absorption by about 10%. When given with food, the amount of tizanidine absorbed from the capsule is about 80% of the amount absorbed from the tablet.
Administration of the capsule contents sprinkled on applesauce is not bioequivalent to intact capsule under fasting conditions and results in a 15–20% increase in peak plasma concentration and AUC and a 15-minute decrease in median lag time and time to achieve peak plasma concentration compared with administration of intact capsule while fasting.
Distribution
Plasma Protein Binding
About 30%.
Elimination
Metabolism
Extensively metabolized in the liver.
Half-life
About 2.5 hours.
Stability
Storage
Oral
Capsules and Tablets
25°C (may be exposed to 15–30°C).
Actions
Centrally acting α2-adrenergic agonist with myotonolytic effects on skeletal muscle.
Exact mechanism in reducing muscle tone and spasm frequency is not clear. Reportedly decreases the frequency and amplitude of muscle spasms (tonic reflexes) that arise in response to muscle stretching in patients with various spinal cord lesions. Appears to reduce spasticity by increasing presynaptic inhibition of motor neurons, leading to reduced facilitation of spinal motor neurons and a resultant decrease in muscle tone.
Greatest effects on polysynaptic pathways, with no important effect on monosynaptic spinal reflexes. The drug does not have direct effects on skeletal muscle fibers or the neuromuscular junction.
Shown to have antinociceptive effects in animals, and some reports have suggested that it may improve pain associated with muscle spasm.
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Risk of marked orthostatic hypotension; importance of exercising caution when moving from a supine to a fixed upright position.
Risk of somnolence, which may be additive when taken in conjunction with other CNS depressants; importance of exercising caution when performing activities requiring alertness, including driving a motor vehicle or operating machinery.
Importance of advising patients of potential changes in absorption profile and resulting changes in efficacy and adverse effect profile when taken with food. (See Pharmacokinetics.)
Importance of not discontinuing abruptly because of potential for rebound hypertension and tachycardia.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of advising patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
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