ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : -19 مورد

Tizanidine: Pediatric drug information

Tizanidine: Pediatric drug information
2025© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Tizanidine: Drug information" and "Tizanidine: Patient drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Zanaflex
Brand Names: Canada
  • APO-TiZANidine;
  • GEN-TiZANidine;
  • MINT-Tizanidine;
  • PAL-TiZANidine [DSC]
Therapeutic Category
  • Alpha2-Adrenergic Agonist
Dosing: Pediatric

Dosage guidance:

Dosage form information: The tablet and capsule dosage forms are not bioequivalent when administered with food.

Spasticity associated with cerebral palsy

Spasticity associated with cerebral palsy: Limited data available (Ref): Dosing based on small open-label trials and clinical experience.

Initial dose:

Children 2 to <10 years: Oral: 1 mg at bedtime; titrate as needed.

Children ≥10 years and Adolescents: Oral: 2 mg at bedtime; titrate as needed.

Titration and maintenance dose: Children ≥2 years and Adolescents: Oral: Titrate initial dose upward to reported effective range of 0.3 to 0.5 mg/kg/day in 3 to 4 divided doses; maximum daily dose: 24 mg/day. Note: In adults, when discontinuation of therapy is necessary, doses are gradually tapered by 2 to 4 mg daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no pediatric-specific dosage recommendations; use with caution (tizanidine is primarily renally eliminated); based on experience in adult patients, dosing adjustment suggested.

Dosing: Liver Impairment: Pediatric

There are no pediatric-specific dosage recommendations; based on experience in adult patients, dosing adjustment suggested; use with caution.

Dosing: Adult

(For additional information see "Tizanidine: Drug information")

Dosage guidance:

Dosage form information: Switching between capsules and tablets may alter effect as these preparations are not bioequivalent when administered with food.

Muscle spasm and/or musculoskeletal pain

Muscle spasm and/or musculoskeletal pain (adjunctive therapy) (off-label use):

Note: For skeletal muscle spasm and/or pain (eg, low back pain, neck pain) with muscle spasm, usually in combination with nonsteroidal anti-inflammatory drugs and/or acetaminophen (Ref). In general, muscle relaxants should be used temporarily (eg, for a few days or intermittently for a few days when needed; up to 4 weeks’ duration when necessary) (Ref).

Oral: Initial: 2 to 4 mg every 8 to 12 hours as needed and/or at bedtime; some may benefit by scheduling doses initially. May increase based on response and tolerability up to a maximum dose of 24 mg/day (eg, 4 to 8 mg every 8 hours as needed) (Ref).

Spasticity

Spasticity:

Note: For muscle spasticity due to neurologic injury or disease (eg, multiple sclerosis, stroke, spinal cord injury, traumatic brain injury, amyotrophic lateral sclerosis [ALS]) (Ref).

Oral: Initial: 2 mg once daily usually at bedtime; may increase based on response and tolerability in increments of 2 to 4 mg per day (with a minimum of 1 to 4 days between dose increases) up to a maximum dose of 36 mg/day in 3 or 4 divided doses (Ref). In the treatment of spasticity associated with stroke (eg, hemiplegic shoulder pain), some experts initiate therapy with 2 mg every 8 hours as needed (Ref). In the treatment of spasticity associated with ALS, some experts limit dose to 24 mg/day (Ref).

Discontinuation of therapy: Gradually taper total daily dose by 2 to 4 mg to reduce the risk of rebound symptoms (eg, hypertension, tachycardia, hypertonia), especially in patients receiving high doses (eg, ≥16 mg/day) for long periods (eg, ≥9 weeks) or in patients who have been receiving concomitant opioids (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: Oral:

CrCl ≥60 mL/minute: No dosage adjustment necessary (Ref).

CrCl ≥25 to <60 mL/minute: Initial: No specific dosage adjustment recommended (has not been studied); however, tizanidine is primarily renally eliminated; use with caution. Start at the low end of the dosing range and monitor for side effects with increased doses (Ref).

CrCl <25 mL/minute: Initial: 2 mg once daily; may increase based on response and tolerability by 2 mg per day (with a minimum of 1 to 4 days between dose increases). Use with caution; clearance reduced >50%. If higher doses are necessary, consider increasing the dose instead of increasing dosing frequency (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable (large Vd) (Ref).

Oral: Initial: 2 mg once daily; use with caution, as clearance in patients with severe kidney dysfunction is reduced >50%. Slowly increase based on tolerability and response in 2 mg increments. If higher doses are necessary, consider increasing the dose instead of increasing dosing frequency (Ref).

Peritoneal dialysis: Unlikely to be significantly dialyzable (large Vd) (Ref).

Oral: Initial: 2 mg once daily; use with caution, as clearance in patients with severe kidney dysfunction is reduced >50%. Slowly increase based on tolerability and response in 2 mg increments. If higher doses are necessary, consider increasing the dose instead of increasing dosing frequency (Ref).

CRRT: Unlikely to be significantly dialyzable (large Vd) (Ref).

Oral: Initial: 2 mg once daily; use with caution, as clearance is reduced in patients with kidney dysfunction. Slowly increase based on tolerability and response in 2 mg increments. If higher doses are necessary, consider increasing the dose instead of increasing dosing frequency (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Unlikely to be significantly dialyzable (large Vd) (Ref).

Oral: Initial: 2 mg once daily; use with caution, as clearance is reduced in patients with kidney dysfunction. Slowly increase based on tolerability and response in 2 mg increments. If higher doses are necessary, consider increasing the dose instead of increasing dosing frequency (Ref).

Dosing: Liver Impairment: Adult

Use with caution; reduce dose during initial dose titration. If higher doses are necessary, increase dose instead of increasing dosing frequency. Monitor aminotransferases.

Adverse Reactions (Significant): Considerations
Hepatotoxicity

Asymptomatic, reversible increased liver enzymes (most notably alanine aminotransferase [ALT]) and severe hepatotoxicity have been reported (Ref). Resolution in patients with clinically significant increases in liver enzymes occurs upon discontinuation. In patients with severe hepatotoxicity, recovery has occurred within 1 to 2 months of discontinuation (Ref).

Mechanism: Non–dose-related; unknown, may be due to immunologic reaction (Ref).

Onset: Delayed; reported 2 to 4 months after initiation (Ref). Upon rechallenge, increases in ALT have been reported within 6 days (Ref).

Risk factors:

• Underlying hepatic impairment (Ref)

Hypotension

Reversible hypotension has been demonstrated in 7% to 12% of patients receiving tizanidine (Ref). Orthostatic hypotension has also been reported ((Ref). Hypotension may lead to asthenia, dizziness, syncope, or discontinuation (Ref).

Mechanism: Dose-related; related to the pharmacologic action (ie, alpha-2 adrenergic agonist) (Ref).

Onset: Rapid; occurs within 30 minutes to 6 hours (Ref).

Risk factors:

• Higher doses and rapid titration

• Concurrent CYP1A2 inhibitors (eg, ciprofloxacin is associated with a 10-fold and fluvoxamine with a 33-fold increase in tizanidine concentrations) (Ref)

• Concurrent use of medications that cause hypotension (Ref)

• Underlying hepatic impairment (Child-Pugh score ≥7) (Ref)

Sedation

Non–life-threatening, reversible sedated state occurs in 24% to 50% of patients receiving a standard dose (≤36 mg/day) of tizanidine (Ref). Sedation leading to coma has occurred with tizanidine overdose (Ref).

Mechanism: Dose-related; related to the pharmacologic action (ie, alpha-2 adrenergic agonist) (Ref).

Onset: Rapid; may occur within 60 minutes (Ref).

Risk factors:

• Concurrent use of alcohol

• Concurrent CYP1A2 inhibitors (eg, ciprofloxacin is associated with a 10-fold and fluvoxamine with a 33-fold increase in tizanidine concentrations) (Ref)

• Concurrent CNS depressants (Ref)

• Underlying kidney impairment

Withdrawal syndrome

Abrupt discontinuation of tizanidine has led to potentially life-threatening withdrawal syndrome, including possible dysthermia, hallucinations, hypertension, nausea, tremor, and tachycardia (Ref).

Mechanism: Dose- and time-related (ie, hypersecretion of catecholamines following cessation of alpha-2 agonism) (Ref).

Onset: Rapid; occurs within 12 to 24 hours of cessation (Ref).

Risk factors

• High doses (≥16 mg daily) (Ref).

• Prolonged use (≥9 weeks)

• Abrupt discontinuation (Ref)

• Concurrent cessation of other CNS depressants (eg, baclofen, benzodiazepines, opioids) (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adolescents and adults.

>10%:

Gastrointestinal: Xerostomia (49%)

Nervous system: Asthenia (41%; including fatigue) (table 1), dizziness (16%) (table 2), drowsiness (48%) (table 3)

Tizanidine: Adverse Reaction: Asthenia

Drug (Tizanidine)

Placebo

Dosage Form

Number of Patients (Tizanidine)

Number of Patients (Placebo)

41%

16%

Oral tablets

264

261

Tizanidine: Adverse Reaction: Dizziness

Drug (Tizanidine)

Placebo

Dosage Form

Number of Patients (Tizanidine)

Number of Patients (Placebo)

16%

4%

Oral tablets

264

261

Tizanidine: Adverse Reaction: Drowsiness

Drug (Tizanidine)

Placebo

Dosage Form

Number of Patients (Tizanidine)

Number of Patients (Placebo)

48%

10%

Oral tablets

264

261

1% to 10%:

Gastrointestinal: Constipation (4%), vomiting (3%)

Genitourinary: Urinary frequency (3%), urinary tract infection (10%)

Hepatic: Increased liver enzymes (most notably increased serum alanine aminotransferase) (6%) (table 4)

Tizanidine: Adverse Reaction: Increased Liver Enzymes

Drug (Tizanidine)

Placebo

Dosage Form

Number of Patients (Tizanidine)

Number of Patients (Placebo)

6%

2%

Oral tablets

264

261

Infection: Infection (6%)

Nervous system: Delusion (≤3%), nervousness (3%), speech disturbance (3%), visual hallucination (≤3%)

Neuromuscular & skeletal: Dyskinesia (3%)

Ophthalmic: Amblyopia (≤3%), blurred vision (≤3%)

Respiratory: Flu-like symptoms (3%), pharyngitis (3%), rhinitis (3%)

Postmarketing:

Cardiovascular: Bradycardia (Ref), hypotension (Ref), orthostatic hypotension (Ref), syncope, ventricular tachycardia

Dermatologic: Exfoliative dermatitis, skin rash, Stevens-Johnson syndrome

Hepatic: Hepatitis (Ref), hepatotoxicity (Ref)

Hypersensitivity: Anaphylaxis, angioedema

Nervous system: Depression, hallucination, paresthesia, sedated state (Ref), seizure, tremor, withdrawal syndrome (Ref)

Neuromuscular & skeletal: Arthralgia, muscle spasm

Contraindications

Hypersensitivity (eg, anaphylaxis, angioedema) to tizanidine or any component of the formulation; concomitant use with strong CYP1A2 inhibitors.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in US labeling): Patients requiring spasticity to maintain function (eg, maintenance of upright posture, balance in locomotion).

Warnings/Precautions

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; potential for effects likely due to extensive hepatic metabolism of tizanidine.

• Renal impairment: Use with caution in patients with renal impairment. Clearance decreased significantly in patients with severe impairment (CrCl <25 mL/minute); dose reductions recommended.

Special populations:

• Older adults: Use with caution; clearance decreased fourfold in older adults (≥65 years of age); may increase risk of adverse effects and/or duration of effects. Older adults with severe renal impairment (CrCl <25 mL/minute) may have clearance reduced by >50% compared to healthy older adults.

Other warnings/precautions:

• Food: Food alters absorption profile relative to administration under fasting conditions. In addition, bioequivalence between capsules and tablets is altered by food; capsules and tablets are bioequivalent under fasting conditions, but not under nonfasting conditions.

Product Availability

Ontralfy Oral Solution: FDA approved December 2024; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Ontralfy is indicated for the treatment of spasticity in adults. Consult the prescribing information for additional information.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Zanaflex: 2 mg [DSC], 4 mg [DSC], 6 mg [DSC]

Generic: 2 mg, 4 mg, 6 mg

Tablet, Oral:

Zanaflex: 4 mg

Generic: 2 mg, 4 mg

Generic Equivalent Available: US

Yes

Pricing: US

Capsules (tiZANidine HCl Oral)

2 mg (per each): $1.22 - $2.71

4 mg (per each): $3.43 - $3.44

6 mg (per each): $5.15

Tablets (tiZANidine HCl Oral)

2 mg (per each): $1.22

4 mg (per each): $1.46 - $1.47

Tablets (Zanaflex Oral)

4 mg (per each): $4.30

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 2 mg, 4 mg

Administration: Pediatric

Oral: May be taken with or without food but consistent administration with regard to meals is recommended (due to impact on absorption). Capsules may be opened and contents sprinkled on food (eg, applesauce); however, extent of absorption is increased up to 20% relative to administration of the intact capsule under fasted conditions.

Administration: Adult

Oral: May be administered with or without food but consistent administration with regard to meals is recommended (due to impact on absorption). Capsules may be opened and contents sprinkled on food; however, extent of absorption is increased up to 20% relative to administration of the capsule under fasted conditions.

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Use

Management of spasticity; reserve treatment with tizanidine for daily activities and times when relief of spasticity is most important (FDA approved in adults).

Medication Safety Issues
Sound-alike/look-alike issues:

TiZANidine may be confused with nizatidine, tiaGABine.

Zanaflex may be confused with Xiaflex.

Older Adult: High-Risk Medication:

Tizanidine is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with dementia or delirium (O’Mahony 2023).

Other safety concerns:

Zanaflex capsules and Zanaflex tablets (or generic tizanidine tablets) are not interchangeable in the fed state.

Metabolism/Transport Effects

Substrate of CYP1A2 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor

Aldesleukin: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Alpha2-Agonists: May increase hypotensive effects of TiZANidine. Risk X: Avoid

Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification

Amiodarone: May increase serum concentration of TiZANidine. Risk C: Monitor

Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Amisulpride (Oral): May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor

Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification

Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Beta-Blockers: May increase rebound hypertensive effects of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Alpha2-Agonists may increase AV-blocking effects of Beta-Blockers. Sinus node dysfunction may also be enhanced. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Risk D: Consider Therapy Modification

Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification

Blood Pressure Lowering Agents: May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor

Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Broccoli: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor

Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid

Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification

BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor

Cannabis: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor

Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider Therapy Modification

Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification

Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification

Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification

Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Ciprofloxacin (Systemic): May increase serum concentration of TiZANidine. Risk X: Avoid

CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

CYP1A2 Inducers (Moderate): May decrease serum concentration of TiZANidine. Risk C: Monitor

CYP1A2 Inhibitors (Moderate): May increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with moderate CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification

CYP1A2 Inhibitors (Strong): May increase serum concentration of TiZANidine. Risk X: Avoid

CYP1A2 Inhibitors (Weak): May increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with weak CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification

Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

Diazoxide Choline: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk X: Avoid

Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor

Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dinutuximab Beta: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor

DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification

DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor

Elranatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor

Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Epcoritamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Etrasimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Famotidine: May increase serum concentration of TiZANidine. Risk C: Monitor

Fexinidazole: Bradycardia-Causing Agents may increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid

Filgotinib: May increase serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider Therapy Modification

Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid

Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification

Glofitamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification

Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Ivabradine: Bradycardia-Causing Agents may increase bradycardic effects of Ivabradine. Risk C: Monitor

Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Lacosamide: Bradycardia-Causing Agents may increase AV-blocking effects of Lacosamide. Risk C: Monitor

Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of Landiolol. Risk X: Avoid

Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification

Leniolisib: May increase serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid

Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor

Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification

Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor

Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification

Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor

Midodrine: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mirtazapine: May decrease antihypertensive effects of Alpha2-Agonists. Management: Consider avoiding concurrent use. If the combination cannot be avoided, monitor for decreased effects of alpha2-agonists if mirtazapine is initiated/dose increased, or increased effects if mirtazapine is discontinued/dose decreased. Risk D: Consider Therapy Modification

Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Mosunetuzumab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor

Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid

Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification

Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid

Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification

OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Pacritinib: May increase serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid

Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor

Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor

Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ponesimod: Bradycardia-Causing Agents may increase bradycardic effects of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider Therapy Modification

Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor

Primaquine: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor

Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Ritlecitinib: May increase serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification

ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor

Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor

Serotonin/Norepinephrine Reuptake Inhibitor: May decrease therapeutic effects of Alpha2-Agonists. Risk C: Monitor

Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Siponimod: Bradycardia-Causing Agents may increase bradycardic effects of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider Therapy Modification

Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

Talquetamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Tarlatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Teclistamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid

Tobacco (Smoked): May decrease serum concentration of TiZANidine. Risk C: Monitor

Tricyclic Antidepressants: May decrease antihypertensive effects of Alpha2-Agonists. Management: Consider avoiding this combination. If used, monitor for decreased effects of the alpha2-agonist. Exercise great caution if discontinuing an alpha2-agonist in a patient receiving a TCA. Risk D: Consider Therapy Modification

Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification

Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification

Food Interactions

The tablet and capsule dosage forms are not bioequivalent when administered with food. Food increases both the time to peak concentration and the extent of absorption for both the tablet and capsule. However, maximal concentrations of tizanidine achieved when administered with food were increased by 30% for the tablet, but decreased by 20% for the capsule. Under fed conditions, the capsule is approximately 80% bioavailable relative to the tablet. Management: Administer with or without food, but keep consistent.

Dietary Considerations

Administration with food compared to administration in the fasting state results in clinically-significant differences in absorption and other pharmacokinetic parameters. Patients should be consistent and should not switch administration of the tablets or the capsules between the fasting and nonfasting state. In addition, switching between the capsules and the tablets in the fed state will also result in significant differences. Opening capsule contents to sprinkle on applesauce compared to swallowing intact capsules whole will also result in significant absorption differences. Patients should be consistent with regards to administration.

Reproductive Considerations

Oral contraceptives may decrease the clearance of tizanidine; concomitant use of oral contraception is not recommended by the manufacturer. Consult drug interactions database for details related to management of patients taking tizanidine with CYP1A2 inhibitors (weak).

Pregnancy Considerations

Information related to use of tizanidine in pregnancy is limited (Eleftheriou 2014).

Monitoring Parameters

LFTs at baseline and during use as clinically appropriate (including 1 month after maximum dose achieved); renal function; blood pressure; signs/symptoms of hypotension; mental alertness and hallucinations.

Mechanism of Action

An alpha2-adrenergic agonist agent which decreases spasticity by increasing presynaptic inhibition; effects are greatest on polysynaptic pathways; overall effect is to reduce facilitation of spinal motor neurons.

Pharmacokinetics (Adult Data Unless Noted)

Onset: Single dose (8 mg): Peak effect: 1 to 2 hours

Duration: Single dose (8 mg): 3 to 6 hours

Absorption: Tablets and capsules are bioequivalent under fasting conditions, but not under nonfasting conditions.

Tablets administered with food: Peak plasma concentration is increased by ~30%; time to peak increased by 25 minutes; extent of absorption increased by ~30%.

Capsules administered with food: Peak plasma concentration decreased by 20%; time to peak increased by 2 to 3 hours; extent of absorption increased by ~10%.

Capsules opened and sprinkled on applesauce are not bioequivalent to administration of intact capsules under fasting conditions. Peak plasma concentration and AUC are increased by 15% to 20%; time to peak decreased by 15 minutes.

Distribution: IV: 2.4 L/kg

Protein binding: ~30%

Metabolism: Extensively hepatic via CYP1A2 to inactive metabolites

Bioavailability: ~40% (extensive first-pass metabolism)

Half-life elimination: ~2.5 hours

Time to peak, serum:

Fasting state: Capsule, tablet: 1 hour

Fed state: Capsule: 3 to 4 hours, Tablet: 1.5 hours

Excretion: Urine (60%); feces (20%)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Clearance is reduced more than 50% in elderly patients with renal function impairment (creatinine clearance <25 mL/minute) compared with healthy subjects; this may lead to longer duration of clinical effects.

Hepatic function impairment: Extensively metabolized in the liver and significant effects are expected; use not recommended in patients with hepatic impairment.

Older adult: Younger subjects cleared drug 4 times faster than elderly subjects.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Sirdalud;
  • (AR) Argentina: Sirdalud | Tizanidal;
  • (AT) Austria: Sirdalud | Tizagelan | Tizanidin Actavis;
  • (BD) Bangladesh: Relentus | Sirdalud | Tizadine | Tizalud;
  • (BE) Belgium: Sirdalud;
  • (BG) Bulgaria: Musant | Tizanidine;
  • (BR) Brazil: Cloridrato de Tizanidina | Sirdalud;
  • (CH) Switzerland: Sirdalud | Tizanidin Orion | Tizanidine axapharm;
  • (CL) Chile: Sirdalud;
  • (CN) China: Carefufe | Chang bang | Kai lai tong;
  • (CO) Colombia: Airflex | Alertadina | Cimbrar | Impoflex | Lamidon | Mio relax | Miorelax | Myos nor | Myos-nor | Relaxkov | Sirdalud | Tizanidina;
  • (CZ) Czech Republic: Sirdalud;
  • (DE) Germany: Sirdalud;
  • (DO) Dominican Republic: Pirdan | Sirdalud;
  • (EC) Ecuador: Sirdalud;
  • (EE) Estonia: Sirdalud | Tizanidine Teva;
  • (EG) Egypt: Caredalud | Epcidin | Myoldin | Rekan | Roysan | Sirdalud | Smr | Tizyl;
  • (ES) Spain: Sirdalud;
  • (FI) Finland: Sirdalud | Tizagelan | Tizanidin Actavis | Tizanidin Alternova | Tizanidin Copyfarm | Tizanidin Orion | Tizanidin Teva;
  • (FR) France: Sirdalud;
  • (GB) United Kingdom: Tizanidine | Tizanidine kent | Tizanidine niche | Zanaflex;
  • (GR) Greece: Sirdalud;
  • (HK) Hong Kong: Sirdalud;
  • (HR) Croatia: Tizanidin Altamedics;
  • (HU) Hungary: Sirdalud | Tizagelan;
  • (ID) Indonesia: Myores | Phardex | Sirdalud | Tizacom | Tizanidine | Zitanid;
  • (IE) Ireland: Tizaflex | Tizanidine niche | Zanaflex;
  • (IN) India: Prinim t | Sirdalud | Tizadin | Tizan | Tizpa;
  • (IT) Italy: Navizan | Sirdalud | Tizagelan | Tizanidina;
  • (JO) Jordan: Sirdalud;
  • (JP) Japan: Astonelin | Astonelin choseido | Dohfarche | Enchinin | Etanaldin | Gibonz | Gibonz mita | Herusenelin | Mekitack | Motonalin | Pelixal | Sevretin | Sevretin merck hoei | Telzanine | Ternelin | Terrelark | Tetorinen | Theorate | Tirolbit | Tizanelin | Tizanidine | Tizanin;
  • (KE) Kenya: Relezin | Sirdalud | Tizigesic;
  • (KR) Korea, Republic of: Sirdalud | Soften | Tizalead;
  • (KW) Kuwait: Sirdalud;
  • (LT) Lithuania: Sirdalud;
  • (LU) Luxembourg: Sirdalud;
  • (LV) Latvia: Sirdalud | Tizanidine Teva;
  • (MA) Morocco: Sirdalud;
  • (MX) Mexico: Nadiamyr | Sirdalud | Sirdalud mr | Tizanidina;
  • (MY) Malaysia: Tizanidine;
  • (NG) Nigeria: Relezin | Sirdalud | Tizanidine;
  • (NL) Netherlands: Sirdalud | Tizanidine;
  • (NO) Norway: Sirdalud | Sirdalud retard | Tizanidin Teva | Zanaflex;
  • (NZ) New Zealand: Sirdalud | Tizanidine;
  • (PE) Peru: Sirdalud;
  • (PH) Philippines: Sirdalud | Ternelax;
  • (PK) Pakistan: Agile | Analar | Arcozid | Cibtaz | Delpoflex | Demzoflex | Dyzo | Efibac | Ezad | Ezidin | Fernor | Kadin | Lentil | Lintiz | Lozeden | Maxlax | Micnic | Movax | Mr x | Mudine | Muscaset | Musidin | Muslex | Mutin | Mylex | Myodine | Myotiz | Nazeden | Nyer | Ob terline | Redeem | Relaxamed | Relaxamed sr | Relaxit | Rexant | Ronelin | Seflex | Skelgesic | Skelwin | Sn skelax | Soneta | Spasfree | Spastiz | Strive | Tandolax | Tanin | Tanzic | Tanzoflex | Tenavax | Terlax | Ternelin | Tezany | Tezany fort | Tiflex | Tigesic | Timzi | Tinadine | Tinex | Tinize | Tizadin | Tizarex | Tizax | Tizaxidine | Tizenax | Tizgic | Tizilex | Tizirel | Tizodine | Tizpa | Tonsic | Trajin | Trans-Din | Turz | Unixidine | Xantix | Xinasia | Zadin | Zanaflex | Zandic | Zandin | Zaniflex | Zanita | Zantid | Zenile | Zid | Zinad | Zinlax | Zinzan | Zita;
  • (PL) Poland: Sirdalud | Tizagelan | Tizanidin Teva | Tizanidine Arrow | Tizanor;
  • (PR) Puerto Rico: Tizanidine | Tizanidine HCL | Zanaflex;
  • (PT) Portugal: Sirdalud | Tizanidina Teva;
  • (PY) Paraguay: Sirdalud | Tizaflex;
  • (QA) Qatar: Relezin | Sirdalud;
  • (RU) Russian Federation: Sirdalud | Sirdalud mr | Tisalud | Tizanidin | Tizanidin Teva | Tizanidine | Tizanidine avexima | Tizanidine sz | Tizanil;
  • (SA) Saudi Arabia: Relezin | Sirdalud | Tilax;
  • (SI) Slovenia: Sirdalud | Tizanidin Teva;
  • (SK) Slovakia: Sirdalud;
  • (TH) Thailand: Sirdalud | Tidar | Tizan | Tonolyte;
  • (TR) Turkey: Devalud | Santadine | Sirdalud;
  • (TW) Taiwan: Sirdalud | Spaslax | Stidine | Tizalin | Tizan;
  • (UA) Ukraine: Sirdalud | Tizalud | Tizanidin ratiopharm;
  • (UG) Uganda: Tizigesic;
  • (UY) Uruguay: Exiflex | Mioflex | Sirdalum | Tiflex | Tizafen | Tizanidal | Tizarelax;
  • (VE) Venezuela, Bolivarian Republic of: Sirdalud | Tizanidina;
  • (VN) Viet Nam: Colthimus | Muslexan | Novalud | Tizanad | Waruwari | Zanastad;
  • (ZM) Zambia: Sirdakud
  1. American Pain Society (APS). Principles of Analgesic Use. 7th ed. Chicago, IL: American Pain Society; 2016.
  2. Ashworth NL, Satkunam LE, Deforge D. Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2012;(2):CD004156. doi:10.1002/14651858.CD004156.pub4. [PubMed 22336799]
  3. Berry H, Hutchinson DR. A multicentre placebo-controlled study in general practice to evaluate the efficacy and safety of tizanidine in acute low-back pain. J Int Med Res. 1988;16(2):75-82. doi:10.1177/030006058801600201. [PubMed 2967780]
  4. Chaugai S, Dickson AL, Shuey MM, et al. Co-prescription of strong CYP1A2 inhibitors and the risk of tizanidine-associated hypotension: a retrospective cohort study. Clin Pharmacol Ther. 2019;105(3):703-709. doi:10.1002/cpt.1233 [PubMed 30223305]
  5. Chou R, Deyo R, Friedly J, et al. Systemic pharmacologic therapies for low back pain: a systematic review for an American College of Physicians clinical practice guideline. Ann Intern Med. 2017;166(7):480-492. doi:10.7326/M16-2458. [PubMed 28192790]
  6. Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage. 2004;28(2):140-175. doi:10.1016/j.jpainsymman.2004.05.002. [PubMed 15276195]
  7. Chou R. Management of subacute and chronic low back pain. Connor RF, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 30, 2024.
  8. Cortes J, Hall B, Redden D. Profound symptomatic bradycardia requiring transvenous pacing after a single dose of tizanidine. J Emerg Med. 2015;48(4):458-460. doi:10.1016/j.jemermed.2014.10.005 [PubMed 25456780]
  9. Creutzfeldt CJ. Neuropalliative care of stroke. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 10, 2022.
  10. Dai AI, Aksoy SN, Demiryürek AT. Comparison of efficacy and side effects of oral baclofen versus tizanidine therapy with adjuvant botulinum toxin type A in children with cerebral palsy and spastic equinus foot deformity. J Child Neurol. 2016;31(2):184-189. doi:10.1177/0883073815587030. [PubMed 25999301]
  11. Dai AI, Wasay M, Awan S. Botulinum toxin type A with oral baclofen versus oral tizanidine: a nonrandomized pilot comparison in patients with cerebral palsy and spastic equinus foot deformity. J Child Neurol. 2008;23(12):1464-1466. doi:10.1177/0883073808319074. [PubMed 19073853]
  12. de Graaf EM, Oosterveld M, Tjabbes T, Stricker BH. A case of tizanidine-induced hepatic injury. J Hepatol. 1996;25(5):772-773. doi:10.1016/s0168-8278(96)80252-2 [PubMed 8938559]
  13. Eleftheriou G, Butera R, Lorenzi F, et al. Tizanidine use in pregnancy. Abstracts from the 2nd International Joined OTIS - ENTIS Conference, September 18-21, 2014, Toronto, Canada. Birth Defects Res A Clin Mol Teratol. 2014;100(7):532. doi:10.1002/bdra.23258 [PubMed 24909848]
  14. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  15. Farrell MC, Biaggioni I, Shibao CA. Neurogenic orthostatic hypotension induced by tizanidine. Clin Auton Res. 2020;30(2):173-175. doi:10.1007/s10286-019-00637-5 [PubMed 31535247]
  16. Galvez-Jimenez N. Symptom-based management of amyotrophic lateral sclerosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 6, 2022.
  17. Gelber DA, Good DC, Dromerick A, Sergay S, Richardson M. Open-label dose-titration safety and efficacy study of tizanidine hydrochloride in the treatment of spasticity associated with chronic stroke. Stroke. 2001;32(8):1841-1846. doi:10.1161/01.str.32.8.1841 [PubMed 11486114]
  18. Gill D, Allam F, Boyle J. Importance of medication reconciliation: tizanidine-induced hepatitis. Am J Ther. 2017 Sep/Oct;24(5):e623-e624. doi:10.1097/MJT.0000000000000497 [PubMed 28323749]
  19. Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ. Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. Clin Pharmacol Ther. 2004;76(6):598-606. doi:10.1016/j.clpt.2004.08.018 [PubMed 15592331]
  20. Haque N, Saha N, Ahmed T, Debnath B, Hossain Mollah A, Rahman E. Comparison of baclofen and tizanidine in reducing spasticity in cerebral palsy: a randomized control trial. Open J Pediatr. 2020;10:617-625. doi:10.4236/ojped.2020.104063
  21. Hennies OL. A new skeletal muscle relaxant (DS 103-282) compared to diazepam in the treatment of muscle spasm of local origin. J Int Med Res. 1981;9(1):62-68. doi:10.1177/030006058100900111. [PubMed 6451461]
  22. Imanaga K, Wajima Z, Inoue T, Ogawa R. Effect of oral tizanidine on local-anesthetic infiltration pain during epidural catheterization. J Nippon Med Sch. 2004;71(2):105-110. doi:10.1272/jnms.71.105 [PubMed 15260084]
  23. Johnson TR, Tobias JD. Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension. J Child Neurol. 2000;15(12):818-819. doi:10.1177/088307380001501211 [PubMed 11198499]
  24. Kao CD, Chang JB, Chen JT, Wu ZA, Shan DE, Liao KK. Hypotension due to interaction between lisinopril and tizanidine. Ann Pharmacother. 2004;38(11):1840-1843. doi:10.1345/aph.1E161 [PubMed 15383642]
  25. Karol DE, Muzyk AJ, Preud'homme XA. A case of delirium, motor disturbances, and autonomic dysfunction due to baclofen and tizanidine withdrawal: a review of the literature. Gen Hosp Psychiatry. 2011;33(1):84.e1-e2. doi:10.1016/j.genhosppsych.2010.10.003 [PubMed 21353141]
  26. Khan R, Nicolas J, and Sachde H. Tizanidine for the management of chronic migraines. Abstract. The Journal of Pain. 2012;S71.
  27. Kitabata Y, Orita H, Kamimura M, et al. Symptomatic bradycardia probably due to tizanidine hydrochloride in a chronic hemodialysis patient. Ther Apher Dial. 2005;9(1):74-77. doi:10.1111/j.1774-9987.2005.00206.x [PubMed 15828911]
  28. Knight CL, Deyo RA, Staiger TO, Wipf JE. Treatment of acute low back pain. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 1, 2022.
  29. Lindsay C, Kouzouna A, Simcox C, Pandyan AD. Pharmacological interventions other than botulinum toxin for spasticity after stroke. Cochrane Database Syst Rev. 2016;10:CD010362. doi:10.1002/14651858.CD010362.pub2. [PubMed 27711973]
  30. Malanga G, Reiter RD, Garay E. Update on tizanidine for muscle spasticity and emerging indications. Expert Opin Pharmacother. 2008;9(12):2209-2215. doi:10.1517/14656566.9.12.2209 [PubMed 18671474]
  31. Masood U, Kahlon A, Mousa O. Clinically significant bradycardia from tizanidine. Am J Ther. 2018;25(3):e385-e386. doi:10.1097/MJT.0000000000000554 [PubMed 28177941]
  32. Momo K, Homma M, Abei M, Hyodo I, Kohda Y. Tizanidine-induced hypotension in patients with liver cirrhosis. Eur J Clin Pharmacol. 2008;64(6):647-648. doi:10.1007/s00228-008-0469-7 [PubMed 18320182]
  33. Montané E, Vallano A, Laporte JR. Oral antispastic drugs in nonprogressive neurologic diseases: a systematic review. Neurology. 2004;63(8):1357-1363. doi:10.1212/01.wnl.0000141863.52691.44 [PubMed 15505149]
  34. Nair KP, Marsden J. The management of spasticity in adults. BMJ. 2014;349:g4737. doi:10.1136/bmj.g4737. [PubMed 25096594]
  35. Nance PW, Bugaresti J, Shellenberger K, Sheremata W, Martinez-Arizala A. Efficacy and safety of tizanidine in the treatment of spasticity in patients with spinal cord injury. North American Tizanidine Study Group. Neurology. 1994;44(11 Suppl 9):S44-51. [PubMed 7970010]
  36. O'Mahony D, Cherubini A, Guiteras AR, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 3. Eur Geriatr Med. 2023;14(4):625-632. doi:10.1007/s41999-023-00777-y [PubMed 37256475]
  37. Oleszek JL, Davidson LT. Spasticity. In: Kliegman RM, St. Geme J, eds. Nelson Textbook of Pediatrics. 21st ed. Saunders Elsevier; 2020:chap 730.
  38. Otero-Romero S, Sastre-Garriga J, Comi G, et al. Pharmacological management of spasticity in multiple sclerosis: Systematic review and consensus paper. Mult Scler. 2016;22(11):1386-1396. doi:10.1177/1352458516643600. [PubMed 27207462]
  39. Pareek A, Chandurkar N, Chandanwale AS, Ambade R, Gupta A, Bartakke G. Aceclofenac-tizanidine in the treatment of acute low back pain: a double-blind, double-dummy, randomized, multicentric, comparative study against aceclofenac alone. Eur Spine J. 2009;18(12):1836-1842. doi:10.1007/s00586-009-1019-4. [PubMed 19421791]
  40. Patel DR, Soyode O. Pharmacologic interventions for reducing spasticity in cerebral palsy. Indian J Pediatr. 2005;72(10):869-872. [PubMed 16272661]
  41. Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society, Delgado MR, Hirtz D, Aisen M, et al. Practice parameter: pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2010;74(4):336-343. doi:10.1212/WNL.0b013e3181cbcd2f [PubMed 20101040]
  42. Refer to manufacturer's labeling.
  43. Saper JR, Winner PK, Lake AE 3rd. An open-label dose-titration study of the efficacy and tolerability of tizanidine hydrochloride tablets in the prophylaxis of chronic daily headache. Headache. 2001;41(4):357-368. doi:10.1046/j.1526-4610.2001.111006357.x [PubMed 11318882]
  44. Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev. 2003;(4):CD001332. doi:10.1002/14651858.CD001332. [PubMed 14583932]
  45. Sirdalud Ternelin Asia-Pacific Study Group. Efficacy and gastroprotective effects of tizanidine plus diclofenac versus placebo plus diclofenac in patients with painful muscle spasms. Curr Ther Res. 1998;59(1):13-22. [PubMed Sirdalud.1998]
  46. Spiller HA, Bosse GM, Adamson LA. Retrospective review of tizanidine (zanaflex) overdose. J Toxicol Clin Toxicol. 2004;42(5):593-596. doi:10.1081/clt-200026978 [PubMed 15462150]
  47. Suárez-Lledó A, Padullés A, Lozano T, Cobo-Sacristán S, Colls M, Jódar R. Management of tizanidine withdrawal syndrome: a case report. Clin Med Insights Case Rep. 2018;11:1179547618758022. doi:10.1177/1179547618758022 [PubMed 29467587]
  48. Taricco M, Pagliacci MC, Telaro E, Adone R. Pharmacological interventions for spasticity following spinal cord injury: results of a Cochrane systematic review. Eura Medicophys. 2006;42(1):5-15. [PubMed 16565680]
  49. Tizanidine [prescribing information]. Chestnut Ridge, NY: Par Pharmaceutical; May 2017.
  50. Tizanidine [product monograph]. Mississauga, Ontario, Canada: Mint Pharmaceuticals; March 2023.
  51. van Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM; Cochrane Back Review Group. Muscle relaxants for nonspecific low back pain: a systematic review within the framework of the Cochrane Collaboration. Spine (Phila Pa 1976). 2003;28(17):1978-1992. doi:10.1097/01.BRS.0000090503.38830.AD. [PubMed 12973146]
  52. Wagstaff AJ, Bryson HM. Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997;53(3):435-452. doi:10.2165/00003495-199753030-00007 [PubMed 9074844]
  53. Wallace JD. Summary of combined clinical analysis of controlled clinical trials with tizanidine. Neurology. 1994;44(11 Suppl 9):S60-S68. [PubMed 7970013]
  54. Zanaflex (tizanidine) [prescribing information]. Georgetown, Grand Cayman: Legacy Pharma; November 2024.
Topic 112669 Version 511.0