Tizanidine

Mechanism-of-action classes: Adrenergic alpha2-Agonists; Cytochrome P450 1A2 Inhibitors.

• Tizanidine is indicated for the treatment of spasticity in adults. Tizanidine is a central alpha-2-adrenergic agonist indicated for the treatment of spasticity.

• Tizanidine is contraindicated in patients: • taking strong CYP1A2 inhibitors [see Drug Interactions ( 7.1 )]. • with a history of hypersensitivity to tizanidine or the ingredients in tizanidine tablets.contraindicated

Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved. ( 2.1 ) Recommended starting dose: 2 mg by mouth every 6 to 8 hours, as needed, up to a maximum of 3 doses in 24 hours ( 2.2 ) Dosage can be increased by 2 mg to 4 mg per dose every 1 to 4 days; maximum total daily dosage is 36 mg ( 2.2 ) Tizanidine pharmacokinetics differs between tablets and capsules, and when taken with or without food. These differences could result in a change in tolerability and control of symptoms. Consistent administration with respect to food is recommended. If substitution between dosage forms is necessary, take into consideration these pharmacokinetic differences. ( 2.2 , 2.6 , 12.3 ) Patients with renal impairment (creatinine clearance <25 mL/min) or hepatic impairment: use lower individual doses during titration.If higher doses are required, individual doses rather than dosing frequency should be increased. ( 2.3 , 2.4 ) To discontinue tizanidine tablets, decrease dose slowly to minimize the risk of withdrawal adverse reactions ( 2.5 ) 2.1 Recommended Evaluation and Testing Before and After Initiating Tizanidine Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved [see Warnings and Precautions ( 5.2 )]. 2.2 Recommended Dosage The recommended starting dose is 2 mg by mouth every 6 to 8 hours, as needed, to a maximum of three doses in 24 hours. Dosage can be gradually increased every 1 to 4 days by 2 mg to 4 mg at each dose based on clinical response and tolerability.

Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; tizanidine should not be used with other α 2 -adrenergic agonists ( 5.1 , 7.5 ) Risk of liver injury: monitor ALTs; discontinue tizanidine if liver injury occurs ( 5.2 ) Sedation: Tizanidine may interfere with everyday activities; sedative effects of tizanidine, alcohol, and other central nervous system (CNS) depressants are additive ( 5.3 , 7.4 ) Hallucinations: consider discontinuation of tizanidine ( 5.4 ) 5.1 Hypotension Tizanidine is an α 2 -adrenergic agonist that can produce hypotension [see Adverse Reactions ( 6.1 ) and Drug Interactions ( 7.5 )] . Syncope has been reported in patients treated with tizanidine in the postmarketing setting. The risk of hypotension may be minimized by dose titration; monitoring for signs and symptoms of hypotension prior to dosage increase may minimize the risks associated with hypotension. In addition, patients moving from a supine to fixed upright position may be at increased risk for hypotension and orthostatic effects. Monitor for hypotension when tizanidine is used in patients receiving concurrent antihypertensive therapy. It is not recommended that tizanidine be used with other α 2 -adrenergic agonists. Clinically significant hypotension (decreases in both systolic and diastolic pressure) has been reported with concomitant administration of tizanidine and strong CYP1A2 inhibitors [see Clinical Pharmacology ( 12.3 )] .

The following clinically significant adverse reactions are described elsewhere in other sections of the prescribing information: • Hypotension [see Warnings and Precautions ( 5.1 )] • Liver Injury [see Warnings and Precautions ( 5.2 )] • Sedation [see Warnings and Precautions ( 5.3 )] • Hallucinosis/Psychotic-Like Symptoms [see Warnings and Precautions ( 5.4 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] • Withdrawal Adverse Reactions [ see Warnings and Precautions ( 5.6 )] The most common adverse reactions (greater than 10% of patients taking tizanidine and greater than in patients taking placebo) were dry mouth, somnolence, asthenia, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. The safety of tizanidine has been evaluated in three double-blind, randomized, placebo-controlled clinical studies [see Clinical Studies ( 14 )] . Two studies were conducted in patients with multiple sclerosis and one in patients with spinal cord injury.

Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) Geriatric use: Tizanidine should be used with caution in elderly patients because clearance is decreased four-fold ( 8.5 ) 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of tizanidine tablets in pregnant women. In animal studies, administration of tizanidine during pregnancy resulted in developmental toxicity (embryofetal and postnatal offspring mortality and growth deficits) at doses less than those used clinically, which were not associated with maternal toxicity (see Animal Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of tizanidine (0.3 to 100 mg/kg/day) to pregnant rats during the period of organogenesis resulted in embryofetal and postnatal offspring mortality and reductions in body weight at doses of 30 mg/kg/day and above. Maternal toxicity was observed at the highest dose tested. The no-effect dose for embryofetal developmental toxicity in rats (3 mg/kg/day) is similar to the maximum recommended human dose (MRHD) of 36 mg/day on a body surface area (mg/m 2 ) basis.

A review of the safety surveillance database revealed cases of intentional and accidental tizanidine overdose. Some of the cases resulted in fatality and many of the intentional overdoses were with multiple drugs, including CNS depressants. The clinical manifestations of tizanidine overdose were consistent with its known pharmacology. In the majority of cases, a decrease in sensorium was observed including lethargy, somnolence, confusion, and coma. Depressed cardiac function is also observed including most often bradycardia and hypotension. Respiratory depression is another common feature of tizanidine overdose. Should overdose occur, ensure the adequacy of an airway and monitor cardiovascular and respiratory function. Dialysis is not likely to be an efficient method of removing tizanidine from the body [see Description ( 11 )] . In general, symptoms resolve within one to three days following discontinuation of tizanidine and administration of appropriate therapy. Because of the similar mechanism of action, symptoms and management of tizanidine overdose are similar to that following clonidine overdose.

• Nov 27, 1996NDANDA020397Legacy Pharma Usa
• Jul 3, 2002ANDAANDA076286Dr Reddys Labs Inc
• Aug 29, 2002NDANDA021447Legacy Pharma Usa
• Sep 29, 2003ANDAANDA076416Sun Pharm Inds Inc
• Jan 16, 2004ANDAANDA076533Apotex
• Feb 3, 2012ANDAANDA078868Apotex Inc
• Nov 28, 2012ANDAANDA091283Unichem Labs Ltd
• Dec 12, 2024NDANDA216190Fidelity Biopharma

1. 1Fatigue3,1497.8%
2. 2Pain3,0087.5%
3. 3Nausea2,9477.3%
4. 4Drug Ineffective2,7936.9%
5. 5Headache2,6346.5%
6. 6Fall2,2885.7%
7. 7Diarrhoea1,9144.7%
8. 8Dizziness1,8814.7%
9. 9Arthralgia1,5763.9%
10. 10Dyspnoea1,5763.9%
11. 11Vomiting1,5613.9%
12. 12Off Label Use1,5443.8%
13. 13Asthenia1,5173.8%
14. 14Anxiety1,4423.6%
15. 15Depression1,4423.6%

The 10 most recently updated of 41 ClinicalTrials.gov registrations naming Tizanidine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Interaction of CYP2B6 Genotype and Efavirenz With Methadone and Tizanidine PK
  Recruiting · Early phase 1 · Interventional · 60 enrolled · Indiana University
  NCT05789173updated 2026-05-29
• Effect of Neural Constraints on Movement in Stroke
  Recruiting · Early phase 1 · Interventional · 64 enrolled · Northwestern University
  NCT06666673updated 2026-05-22
• Tizanidine and Acoustic Reflex
  Completed · Interventional · 48 enrolled · Uşak University
  NCT07309354updated 2026-05-07
• CARES (Comprehensive Analgesic, Recovery, and Education Support) for Surgery Trial
  Recruiting · Phase 3 · Interventional · 375 enrolled · Stanford University
  NCT06027099updated 2026-05-06
• Opioid-Free Pain Protocol After Shoulder Arthroplasty
  Active not recruiting · Phase 4 · Interventional · 83 enrolled · Henry Ford Health System
  NCT05488847updated 2026-02-10
• Efficacy and Safety of Pregabalin/Tizanidine vs. Pregabalin in Patients With Fibromyalgia
  Not yet recruiting · Interventional · 164 enrolled · Beijing Tiantan Hospital
  NCT07382921updated 2026-02-04
• Bi-level Erector Spinae Plane Block and Pre-emptive Oral Tizanidine for Analgesia After Mastectomy Surgery
  Completed · Interventional · 90 enrolled · Mansoura University
  NCT07022353updated 2026-01-27
• Comparison of Analgesic Efficacy of Intrathecal Levobupivacaine With and Without Oral Tizanidine in Lower Limb Surgeries: A Prospective Randomized Study
  Completed · Phase 4 · Interventional · 64 enrolled · All India Institute of Medical Sciences
  NCT07310628updated 2026-01-09
• Efficacy and Safety of Etoricoxib/Tizanidine Versus Etoricoxib for Acute Low Back Pain Associated to Muscle Spasm
  Completed · Phase 3 · Interventional · 136 enrolled · Laboratorios Silanes S.A. de C.V.
  NCT06863662updated 2026-01-09
• Effect of Tizanidine on Postoperative Urinary Retention After Sacrospinous Suspension
  Completed · Phase 3 · Interventional · 20 enrolled · Endeavor Health
  NCT06258785updated 2025-11-24

Ranked by 2D fingerprint (Tanimoto) similarity over PubChem structures. Structural proximity only — not a claim of therapeutic equivalence.

• PropylthiouracilThyroid Hormone Synthesis Inhibitor78%

Frequently asked questions

How does Tizanidine work?

Mechanism-of-action classes: Adrenergic alpha2-Agonists; Cytochrome P450 1A2 Inhibitors.

What is Tizanidine used for?

According to FDA labeling, Tizanidine carries indications including: Tizanidine is indicated for the treatment of spasticity in adults. Tizanidine is a central alpha-2-adrenergic agonist indicated for the treatment of spasticity.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tizanidine?

Tizanidine is classified as Other centrally acting agents, Central alpha-2 Adrenergic Agonist, Adrenergic alpha2-Agonists, Cytochrome P450 1A2 Inhibitors, Decreased Central Nervous System Organized Electrical Activity, Decreased Striated Muscle Contraction.

What are the brand names for Tizanidine?

Tizanidine is marketed under brand names including Ontralfy, Zanaflex.

What are the contraindications for Tizanidine?

Tizanidine labeling lists contraindications including: Tizanidine is contraindicated in patients: • taking strong CYP1A2 inhibitors [see Drug Interactions ( 7.1 )]. • with a history of hypersensitivity to tizanidine or the ingredients in tizanidine tablets.. Always consult the full prescribing information and a clinician.