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Tizanidine: Drug information

Tizanidine: Drug information
(For additional information see "Tizanidine: Patient drug information" and see "Tizanidine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Zanaflex
Brand Names: Canada
  • APO-TiZANidine;
  • GEN-TiZANidine;
  • MINT-Tizanidine;
  • PAL-TiZANidine [DSC]
Pharmacologic Category
  • Alpha2-Adrenergic Agonist
Dosing: Adult

Dosage guidance:

Dosing: Patients more sensitive to sedating and other CNS adverse effects (eg, older adults, patients with organ impairment) may better tolerate a reduced dose, less frequent administration, and/or more gradual titration (Ref).

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) (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: Hepatic Impairment: Adult

Avoid use in hepatic impairment; if used, reduce dose during initial dose titration. If higher doses are necessary, increase dose instead of increasing dosing frequency. Monitor aminotransferases.

Dosing: Older Adult

Use with caution; clearance is decreased. Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Tizanidine: Pediatric drug information")

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: Hepatic Impairment: Pediatric

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

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%) (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%) (Khan 2012)

Neuromuscular & skeletal: Dyskinesia (3%)

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

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

Frequency not defined:

Hepatic: Increased serum alanine aminotransferase

Hypersensitivity: Angioedema

Nervous system: Fatigue

Neuromuscular & skeletal: Muscle spasm

Postmarketing:

Cardiovascular: Bradycardia (Cortes 2014, Masood 2018), hypotension (Kao 2004, Momo 2008), orthostatic hypotension (Farrell 2020), syncope, ventricular tachycardia

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

Hepatic: Hepatitis (de Graaf 1996), hepatotoxicity (de Graaf 1996)

Hypersensitivity: Anaphylaxis

Nervous system: Depression, paresthesia, sedated state (Gelber 2001), seizure, tremor, withdrawal syndrome (Suárez-Lledó 2018)

Neuromuscular & skeletal: Arthralgia

Contraindications

Concomitant therapy with potent CYP1A2 inhibitors (eg, ciprofloxacin, fluvoxamine).

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): Hypersensitivity to tizanidine or any component of the formulation; patients requiring spasticity to maintain function (eg, maintenance of upright posture, balance in locomotion).

Warnings/Precautions

Disease-related concerns:

• Hepatic impairment: Use not recommended 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.

Dosage Forms: US

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

Capsule, Oral:

Zanaflex: 2 mg, 4 mg, 6 mg

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

Capsules (Zanaflex Oral)

2 mg (per each): $4.34

4 mg (per each): $5.50

6 mg (per each): $8.25

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): $4.09

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: Adult

Oral: 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.

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.

Use: Labeled Indications

Spasticity: Management of spasticity; reserve treatment with tizanidine for daily activities and times when relief of spasticity is most important.

Use: Off-Label: Adult

Muscle spasm and/or musculoskeletal pain (adjunctive therapy)

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

TiZANidine may be confused with nizatidine, tiaGABine.

Zanaflex may be confused with Xiaflex.

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

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

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect 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 the serum concentration of TiZANidine. Risk C: Monitor therapy

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Beta-Blockers: Alpha2-Agonists may enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. 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 enhance the CNS depressant effect 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 enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

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

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect 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

Chlormethiazole: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

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

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

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

CYP1A2 Inhibitors (Moderate): May increase the serum concentration of TiZANidine. Management: If combined use cannot be avoided, initiate tizanidine in adults at 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification

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

CYP1A2 Inhibitors (Weak): May increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification

Daridorexant: May enhance the CNS depressant effect 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

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy

DroPERidol: May enhance the CNS depressant effect 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 enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

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

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

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination

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

Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect 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 enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect 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 the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect 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 enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Lemborexant: May enhance the CNS depressant effect 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 the serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect 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

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirtazapine: May diminish the antihypertensive effect 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 enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect 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 enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect 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

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect 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 enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

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

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect 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 enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect 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 enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the therapeutic effect of Alpha2-Agonists. Risk C: Monitor therapy

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect 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 enhance the CNS depressant effect 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 the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

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

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

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

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Tricyclic Antidepressants: May diminish the antihypertensive effect 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect 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.

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).

Breastfeeding Considerations

It is not known if tizanidine is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

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.

Monitoring Parameters

Monitor LFTs at baseline and during use (including 1 month after maximum dose achieved) or if hepatic injury suspected; BP (including prior to dose increase); renal function; mental alertness.

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;
  • (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;
  • (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 | 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 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 | Sirdalud;
  • (TW) Taiwan: Sirdalud | Spaslax | Stidine | Tizalin | Tizan;
  • (UA) Ukraine: Sirdalud | Tizalud | Tizanidin ratiopharm;
  • (UY) Uruguay: Mioflex | Sirdalum | Tiflex | Tizafen;
  • (VE) Venezuela, Bolivarian Republic of: Sirdalud | Tizanidina;
  • (VN) Viet Nam: Colthimus | Novalud | Waruwari;
  • (ZM) Zambia: Sirdakud
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