TiZANidine (Lexi-Drugs)

Pronunciation

(tye ZAN i deen)

Brand Names: US

Zanaflex

Brand Names: Canada

GEN-TiZANidine; MYLAN-TiZANidine [DSC]; PAL-TiZANidine

Pharmacologic Category

Alpha2-Adrenergic Agonist

Dosing: Adult

Muscle spasticity: Oral: Initial: 2 mg up to 3 times daily (at 6- to 8-hour intervals) as needed; may increase based on response and tolerability in 2 to 4 mg increments per dose (with a minimum of 1 to 4 days between dose increases); maximum dose: 36 mg/day. Note: Single doses >16 mg have not been studied.

Discontinuation of therapy: Gradually taper dose by 2 to 4 mg daily.

Dosing: Geriatric

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

Dosing: Renal Impairment: Adult

CrCl ≥25 mL/minute: No dosage adjustment provided in manufacturer’s labeling; however, caution may be needed as creatinine clearance decreases.

CrCl <25 mL/minute: Use with caution; clearance reduced >50%. During initial dose titration, use reduced doses. If higher doses are necessary, increase dose instead of increasing dosing frequency.

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: Pediatric

Note:The tablet and capsule dosage forms are not bioequivalent when administered with food.

Spasticity associated with cerebral palsy: Limited data available (Dai 2008; Dai 2016; Kliegman 2016; Patel 2005): Dosing based on small open label trials and clinical experience; tizanidine was used in combination with adjunct botulinum toxin therapy

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.

Dosing: Renal Impairment: Pediatric

There are no pediatric specific dosage recommendations; use with caution; 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: Labeled Indications

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

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

American Academy of Neurology and the Practice Committee of the Child Neurology Society, “Practice Parameter: Pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review)” 2010.

Administration: 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 should be consistent with regards to administration. 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 capsule under fasted conditions.

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.

Storage/Stability

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

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dry mouth, fatigue, or loss of strength and energy. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain), severe dizziness, passing out, confusion, hallucinations, mood changes, behavioral changes, bradycardia, chills, or pharyngitis (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Other safety concerns:
Contraindications

Concomitant therapy with ciprofloxacin or fluvoxamine (potent CYP1A2 inhibitors)

Warnings/Precautions

Concerns related to adverse effects:

• Hepatic effects: Potential for hepatotoxicity; monitor aminotransferases prior to and during use or if hepatic injury is suspected.

• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, angioedema, respiratory compromise, and urticaria have been reported with use. Patients with signs and symptoms of allergic reactions should discontinue therapy.

• Hypotension: Significant hypotension and syncope may occur; use with caution in patients at risk for severe hypotensive effects (eg, patients taking concurrent medications which may predispose to hypotension). Minimize effects by titrating dose and monitoring for signs and symptoms of hypotension prior to dose increase.

• Sedation: Sedation may occur; use with caution in patients at risk for sedative effects (eg, patients taking concurrent CNS depressants); patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Visual hallucinations: Use has been associated with visual hallucinations or delusions; use caution in patients with psychiatric disorders. Consider discontinuation of therapy if hallucinations occur.

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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.

Special populations:

• Elderly: Use with caution; clearance decreased fourfold in the elderly; may increase risk of adverse effects and/or duration of effects. Elderly with severe renal impairment (CrCl <25 mL/minute) may have clearance reduced by >50% compared to healthy elderly subjects.

Other warnings/precautions:

• Abrupt withdrawal: Withdrawal resulting in rebound hypertension, tachycardia, and hypertonia may occur upon discontinuation; doses should be decreased slowly, particularly in patients taking concomitant opioids or receiving high doses (20-28 mg daily) for prolonged periods (≥9 weeks).

• 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.

Geriatric Considerations

Since elderly commonly have renal function of CrCl <30 mL/minute, creatinine clearance should be estimated before dosing this medication. Low doses should be started initially because of the possibility of CNS effects.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.

Breast-Feeding Considerations

Excretion in breast milk is unknown, but expected due to lipid solubility.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

>10%:

Cardiovascular: Hypotension (16% to 33%)

Central nervous system: Drowsiness (48% to 92%), dizziness (16% to 45%)

Gastrointestinal: Xerostomia (49% to 88%)

Neuromuscular & skeletal: Asthenia (41% to 78%)

1% to 10%:

Cardiovascular: Bradycardia (2% to 10%)

Central nervous system: Nervousness (3%), speech disturbance (3%), delusion (≤3%), visual hallucination (≤3%)

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

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

Hepatic: Abnormal hepatic function tests (6%)

Infection: Infection (6%)

Neuromuscular & skeletal: Dyskinesia (3%)

Ophthalmic: Blurred vision (3%)

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

Frequency not defined:

Central nervous system: Drug withdrawal, sedated state

Hypersensitivity: Hypersensitivity reaction

<1%, postmarketing, and/or case reports: Anaphylaxis, arthralgia, depression, exfoliative dermatitis, fatigue, hepatitis, hepatotoxicity, muscle spasm, paresthesia, seizure, skin rash, Stevens-Johnson syndrome, syncope, tremor, ventricular tachycardia

Metabolism/Transport Effects

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

Drug Interactions 

Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). 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 amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

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

Angiotensin-Converting Enzyme Inhibitors: TiZANidine may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. 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

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). 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. Exceptions: Levobunolol; Metipranolol. Risk D: Consider therapy modification

Blonanserin: CNS Depressants may enhance the CNS depressant effect of 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

Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking 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

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

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. 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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

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

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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. Exceptions are discussed in separate monographs. 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 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

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

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

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

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

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

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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

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

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

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

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

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

Lisinopril: TiZANidine may enhance the hypotensive effect of Lisinopril. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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 adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

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: 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

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

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

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

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

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. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

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

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. 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

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

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the antihypertensive effect of Alpha2-Agonists. 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.Risk D: Consider therapy modification

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. 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

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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

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

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

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. 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

Vemurafenib: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs.Risk D: Consider therapy modification

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

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.

Monitoring Parameters

Monitor liver function (aminotransferases) at baseline and 1 month after maximum dose achieved or if hepatic injury suspected; blood pressure; renal function

Advanced Practitioners Physical Assessment/Monitoring

May cause hypotension; monitor blood pressure periodically. Do not discontinue medication abruptly; can cause hypertension and tachycardia.

Nursing Physical Assessment/Monitoring

May cause hypotension; monitor blood pressure periodically. Do not discontinue medication abruptly; can cause hypertension and tachycardia.

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 [scored]

Generic: 2 mg, 4 mg

Dosage Forms: Canada

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

Tablet, Oral:

Generic: 2 mg, 4 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • M03BX02
Generic Available (US)

Yes

Pricing: US

Capsules (tiZANidine HCl Oral)

2 mg (per each): $2.71

4 mg (per each): $3.44

6 mg (per each): $5.15

Capsules (Zanaflex Oral)

2 mg (per each): $3.28

4 mg (per each): $4.16

6 mg (per each): $6.24

Tablets (tiZANidine HCl Oral)

2 mg (per each): $1.22 – $2.13

4 mg (per each): $1.47 – $2.55

Tablets (Zanaflex Oral)

4 mg (per each): $3.10

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.

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.

Pharmacodynamics/Kinetics

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%)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: 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.

Geriatric: Younger subjects cleared drug 4 times faster than elderly subjects.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Significant xerostomia (normal salivary flow resumes upon discontinuation).

Effects on Bleeding

No information available to require special precautions

Index Terms

Sirdalud; Tizanidine HCl

FDA Approval Date
November 27, 1996
References

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]

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]

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, 2010, 74(4):336-43.[PubMed 20101040]

Kliegman RM, Stanton BMD, St. Geme J, Schor NF, eds. Nelson’ s Textbook of Pediatrics. 20th ed. Philadelphia, PA: Saunders Elsevier; 2016.

Patel DR, Soyode O. Pharmacologic interventions for reducing spasticity in cerebral palsy. Indian J Pediatr. 2005;72(10):869-872.[PubMed 16272661]

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]

Saper JR, Lake AE 3rd, Cantrell DT, et al, “Chronic Daily Headache Prophylaxis With Tizanidine: A Double-Blind, Placebo-Controlled, Multicenter Outcome Study,” Headache, 2002, 42(6):470-82.[PubMed 12167135]

Tizanidine [prescribing information]. Chestnut Ridge, NY: Par Pharmaceutical; May 2017.

Zanaflex (tizanidine) [prescribing information]. Ardsley, NY: Accorda Therapeutics, Inc; November 2013.

Zanaflex (tizanidine) [prescribing information]. Zug, Switzerland: Covis Pharma; February 2018.

Brand Names: International

KaiLaiTong (CN); Mio-Relax (CO); Musant (BG); Musrel (LK); Myores (ID); Myos-Nor (CO); Myoxyl (LK); Phardex (ID); Rekan (EG); Relentus (BD); Remus (BD); Sirdalud (AE, AR, AT, BB, BE, BF, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CO, CY, CZ, DE, DK, EE, EG, ES, ET, FI, FR, GH, GM, GN, GR, GY, HK, ID, IL, IN, IQ, IR, IT, JM, JO, KE, KR, KW, LB, LR, LT, LU, LV, LY, MA, ML, MR, MT, MU, MW, MX, NE, NG, NL, NO, OM, PE, PH, PL, PR, PT, PY, QA, RU, SA, SC, SD, SE, SI, SK, SL, SN, SR, SY, TH, TN, TR, TT, TW, TZ, UA, UG, VE, VN, YE, ZA, ZM, ZW); Sirdalud MR (CH, MX, NL); Sirdalud Retard (DK, FI); Sirdalum (UY); Spaslax (TW); Stidine (TW); Ternelin (JP); Tilax (QA); Tizadin (BD); Tizalin (TW); Tizalud (UA); Tizan (TH); Tizanac (BD); Tizarid (KR); Tizigesic (LK); Tizyl (EG); Tonolyte 2 (TH); Tonolyte 4 (TH); Zanaflex (IE); Zinadur (CR, DO, GT, HN, NI, PA, SV); Zita (PK); Zitanid (ID)

Tizanidine (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(tye ZAN i deen)

Brand Names: US

Zanaflex

Brand Names: Canada

Zanaflex

What is this drug used for?
  • It is used to calm muscles.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to tizanidine or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking any of these drugs: Ciprofloxacin or fluvoxamine.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Do not change from the capsule to the tablet or from the tablet to the capsule.
  • Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
  • Very bad dizziness or passing out.
  • Feeling confused.
  • Hallucinations (seeing or hearing things that are not there).
  • Mood changes.
  • Change in the way you act.
  • Slow heartbeat.
  • Fever or chills.
  • Sore throat.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Dry mouth.
  • Feeling sleepy.
  • Feeling tired or weak.
  • Dizziness.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • Take with or without food but take the same way each time. Always take with food or always take on an empty stomach.
What do I do if I miss a dose?
  • If you take this drug on a regular basis, take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Many times this drug is taken on an as needed basis. Do not take more often than told by the doctor.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Tizanidine (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(tye ZAN i deen)

Brand Names: US

Zanaflex

Brand Names: Canada

Zanaflex

What is this drug used for?
  • It is used to calm muscles.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child is taking any of these drugs: Ciprofloxacin or fluvoxamine.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • To lower the chance of feeling dizzy or passing out, have your child rise slowly if your child has been sitting or lying down. Have your child be careful going up and down stairs.
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of side effects. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Do not change from the capsule to the tablet or from the tablet to the capsule.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with your child’s doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
  • Very bad dizziness or passing out.
  • Feeling confused.
  • Hallucinations (seeing or hearing things that are not there).
  • Mood changes.
  • Change in the way your child acts.
  • Slow heartbeat.
  • Fever or chills.
  • Sore throat.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Dry mouth.
  • Feeling sleepy.
  • Feeling tired or weak.
  • Dizziness.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • Give this drug with or without food but give it the same way each time. Always give with food or always give on an empty stomach.
What do I do if my child misses a dose?
  • If your child takes this drug on a regular basis, give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • Many times this drug is given on an as needed basis. Do not give to your child more often than told by the doctor.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.