Tizanidine 2 mg Tablet, 90-count
Other active recalls for Tizanidine (different manufacturers) — 2 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Central alpha-2 Adrenergic Agonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Tizanidine is used to relieve muscle spasms, cramping, and tightness caused by certain conditions including multiple sclerosis (MS, a disease in which the nerves do not function properly and patients may experience weakness, numbness, loss of muscle coordination and problems with vision, speech, and bladder control) and spinal injury. Tizanidine is in a class of medications called skeletal muscle relaxants. It works by slowing action in the brain and nervous system to allow the muscles to relax.
Read the full MedlinePlus article ↗- Tizanidine is a muscle relaxant prescribed to manage spasticity — that's the uncomfortable muscle stiffness, tightness, or spasms that can come with conditions like multiple sclero...
- Yes, it actually matters a lot — and it's different depending on whether you're taking a tablet or a capsule. Food increases how much drug your body absorbs from the tablet, but it...
- Does it matter if I take tizanidine with food or without?
- Very likely, yes — drowsiness is one of the most common side effects and can be significant, especially when you first start or when the dose is being adjusted. It can interfere wi...
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Supplement & herbal interactions
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $0.1130 | $10.17 / 90 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Tizanidine 2 mg 16714-0171-01 | NorthStar | 150 tablets | $0.031 | AB | Availability likely | — |
| Tizanidine 2 mg 50268-0759-15 | AvPAK | 50 tablets | $0.031 | AB | Availability likely | — |
| Tizanidine 2 mg 57664-0502-18 | Sun | 1000 tablets | $0.031 | AB | Availability likely | — |
| Tizanidine 2 mg 68084-0775-25 | American | 30 tablets | $0.031 | AB | Availability likely | — |
| tizanidine 2 mg 00615-8468-39 | NCS | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 29300-0168-05 | Unichem | 500 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 35356-0662-14 | Quality | 14 tablets | — | AB | Discontinued | — |
| Tizanidine 2 mg 43063-0868-12 | PD-Rx | 12 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 50090-0811-00 | A-S | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 50090-2078-00 | A-S | 30 tablets | — | AB | FDA listed | — |
| tizanidine 2 mg 50090-7716-00 | A-S | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 55111-0179-03 | Dr. | 300 tablets | — | AB | FDA listed | — |
| tizanidine 2 mg 60505-0251-01 | Apotex | 100 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 60760-0694-04 | St. | 4 tablets | — | AB | FDA listed | — |
| Tizandine 2 mg 61919-0811-60 | Direct_Rx | 60 tablets | — | AB | Discontinued | — |
| Tizanidine 2 mg 63187-0910-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 63629-2370-01 | Bryant | 1000 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 63629-3209-00 | Bryant | 40 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 63629-7037-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 63629-8533-01 | Bryant | 150 tablets | — | AB | FDA listed | — |
| tizanidine 2 mg 64980-0658-03 | Rising | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 67296-2209-01 | Redpharm | 21 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 67877-0613-05 | Ascend | 500 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 68071-3440-09 | NuCare | 90 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 68788-7991-03 | Preferred | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 70518-3112-00 | REMEDYREPACK | 60 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 70518-3181-00 | REMEDYREPACK | 60 tablets | — | AB | FDA listed | — |
| tizanidine 2 mg 70771-1335-00 | Zydus | 1000 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 71205-0311-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 71335-0424-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 71335-1799-00 | Bryant | 40 tablets | — | AB | FDA listed | — |
| tizanidine 2 mg 71610-0455-09 | Aphena | 9000 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 72162-1641-00 | Bryant | 1000 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 72189-0599-30 | Direct_rx | 30 tablets | — | AB | FDA listed | — |
| tizanidine 2 mg 72578-0096-06 | Viona | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 72789-0326-30 | PD-Rx | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 76420-0228-30 | Asclemed | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 76420-0338-00 | Asclemed | 1000 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 76420-0865-12 | Asclemed | 120 tablets | — | AB | FDA listed | — |
| tizanidine 2 mg 76420-0885-00 | Asclemed | 1000 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mgthis 80425-0187-03 | Advanced | 90 tablets | — | AB | FDA listed | — |
| Tizanidine HCl 2 mg 80425-0425-01 | Advanced | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 80425-0436-01 | Advanced | 30 tablets | — | AB | FDA listed | — |
| tizanidine 2 mg 80425-0500-01 | Advanced | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 82461-0720-60 | Medcore | 60 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 85534-0029-00 | HAWAII | 10 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 67296-2316-04 | Redpharm | 21 tablets | — | AB | FDA listed | — |
| Tizanidine 2 mg 84386-0023-77 | Aurobindo | 150 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 80425-0187-01 | 30 TABLET in 1 BOTTLE (80425-0187-1) | 2013-04-01 | Active |
| 80425-0187-02 | 60 TABLET in 1 BOTTLE (80425-0187-2) | 2023-03-30 | Active |
| 80425-0187-03 You're viewing this | 90 TABLET in 1 BOTTLE (80425-0187-3) | 2023-03-30 | Active |
You're viewing the largest of 3 pack sizes for this product.
Pack size FAQ
What quantity is in NDC 80425-0187-03?
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1. Indications and Usage Section 1 INDICATIONS AND USAGE Tizanidine is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration (2.1)].
⏱️ Dosage and Administration ▾
2. Dosage and Administration Section
2.1Dosing Information Tizanidine tablets may be prescribed with or without food. Once the formulation has been selected and the decision to take with or without food has been made, this regimen should not be altered. Food has complex effects on tizanidine pharmacokinetics, which differ with the different formulations.
Tizanidine Capsules and tizanidine tablets are bioequivalent to each other under fasting conditions (more than 3 hours after a meal), but not under fed conditions (within 30 minutes of a meal). These pharmacokinetic differences may result in clinically significant differences when switching administration of tablet and capsules and when switching administration between the fed or fasted state. These changes may result in increased adverse events, or delayed or more rapid onset of activity, depending upon the nature of the switch.
For this reason, the prescriber should be thoroughly familiar with the changes in kinetics associated with these different conditions [see Clinical Pharmacology (12.3)]. The recommended starting dose is 2 mg. Because the effect of tizanidine peaks at approximately 1 to 2 hours post-dose and dissipates between 3 to 6 hours post-dose, treatment can be repeated at 6 to 8 hour intervals, as needed, to a maximum of three doses in 24 hours.
Dosage can be gradually increased by 2 mg to 4 mg at each dose, with 1 to 4 days between dosage increases, until a satisfactory reduction of muscle tone is achieved. The total daily dose should not exceed 36 mg. Single doses greater than 16 mg have not been studied.
2.2Dosing in Patients with Renal Impairment Tizanidine should be used with caution in patients with renal insufficiency (creatinine clearance < 25 mL/min), as clearance is reduced by more than 50%. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased [see Warnings and Precautions (5.7)].
2.3Dosing in Patients with Hepatic Impairment Tizanidine should be used with caution in patients with any hepatic impairment. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased.
Monitoring of aminotransferase levels is recommended for baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected. [see Use in Specific Populations (8.7)]
2.4Drug Discontinuation If therapy needs to be discontinued, particularly in patients who have been receiving high doses (20 mg to 36 mg daily) for long periods (9 weeks or more) or who may be on concomitant treatment with narcotics, the dose should be decreased slowly (2 mg to 4 mg per day) to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia [see Drug Abuse and Dependence (9.3)].
💊 Dosage Forms and Strengths ▾
3. Dosage Forms and Strengths Tablets Tizanidine tablets USP, 2 mg are white to off-white, round, flat, bevel edged uncoated tablets debossed with "U" and "168" on one side and bisecting score on other. Tizanidine tablets USP, 4 mg are white to off-white, round, flat, bevel edged uncoated tablets debossed with "U" and "169" on one side and quadrisecting score on other.
⛔ Contraindications ▾
4. Contraindications Tizanidine is contraindicated in patients taking potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin [see Drug Interactions (7.1, 7.2)].
⚠️ Warnings and Cautions ▾
5. Warnings and Precautions
5.1Hypotension Tizanidine is an α2-adrenergic agonist that can produce hypotension. Syncope has been reported in the post marketing setting. The chance of significant hypotension may possibly be minimized by titration of the dose and by focusing attention on signs and symptoms of hypotension prior to dose advancement.
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 α2-adrenergic agonists.
Clinically significant hypotension (decreases in both systolic and diastolic pressure) has been reported with concomitant administration of either fluvoxamine or ciprofloxacin and single doses of 4 mg of tizanidine. Therefore, concomitant use of tizanidine with fluvoxamine or with ciprofloxacin, potent inhibitors of CYP1A2, is contraindicated [see Contraindications (4) and Drug Interactions (7.1, 7.2)].
5.2Risk of Liver Injury Tizanidine may cause hepatocellular liver injury. Tizanidine should be used with caution in patients with any hepatic impairment. Monitoring of aminotransferase levels is recommended for baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected. [see Dosage and Administration (2.3) and Use in Specific Populations (8.7)]
5.3Sedation Tizanidine can cause sedation, which may interfere with everyday activity. In the multiple dose studies, the prevalence of patients with sedation peaked following the first week of titration and then remained stable for the duration of the maintenance phase of the study. The CNS depressant effects of tizanidine with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive.
Monitor patients who take tizanidine with another CNS depressant for symptoms of excess sedation. [see Drug Interactions (7.5, 7.6)]
5.4Hallucinosis/Psychotic-Like Symptoms Tizanidine use has been associated with hallucinations. Formed, visual hallucinations or delusions have been reported in 5 of 170 patients (3%) in two North American controlled clinical studies. Most of the patients were aware that the events were unreal.
One patient developed psychosis in association with the hallucinations. One patient among these 5 continued to have problems for at least 2 weeks following discontinuation of tizanidine. Consider discontinuing tizanidine in patients who develop hallucinations.
5.5Interaction with CYP1A2 Inhibitors Because of potential drug interactions, tizanidine is contraindicated in patients taking potent CYP1A2 inhibitors, such as fluvoxamine or ciprofloxacin. Adverse reactions such as hypotension, bradycardia, or excessive drowsiness can occur when tizanidine is taken with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than ciprofloxacin (which is contraindicated), antiarrythmics (amiodarone, mexiletine, propafenone), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine ).
Concomitant use should be avoided unless the necessity for tizanidine therapy is clinically evident. In such a case, use with caution. [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)]
5.6Hypersensitivity Reactions Tizanidine can cause anaphylaxis. Signs and symptoms including respiratory compromise, urticaria, and angioedema of the throat and tongue have been reported. Patients should be informed of the signs and symptoms of severe allergic reactions and instructed to discontinue tizanidine and seek immediate medical care should these signs and symptoms occur. [see Contraindications (4)]
5.7Increased Risk of Adverse Reactions in Patients with Renal Impairment Tizanidine should be used with caution in patients with renal insufficiency (creatinine clearance < 25 mL/min), as clearance is reduced by more than 50%. In these patients, durin…
🤒 Adverse Reactions ▾
6. Adverse Reactions The following 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 (5.6)]
6.1Clinical 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. Three double-blind, randomized, placebo controlled -clinical studies were conducted to evaluate the effect of tizanidine on spasticity control. Two studies were conducted in patients with multiple sclerosis and one in patients with spinal cord injury.
Each study had a 13-week active treatment period which included a 3-week titration phase to the maximum tolerated dose up to 36 mg/day in three divided doses, a 9-week plateau phase where the dose of tizanidine was held constant and a 1-week dose tapering. In all, 264 patients received tizanidine and 261 patients received placebo. Across the three studies patient ages ranged from 15–69 years and 51.4 percent were women.
The median dose during the plateau phase ranged from 20–28 mg/day. The most frequent adverse reactions reported in multiple dose, placebo-controlled clinical studies involving 264 patients with spasticity were dry mouth, somnolence/sedation, asthenia (weakness, fatigue and/or tiredness) and dizziness. Three-quarters of the patients rated the events as mild to moderate and one-quarter of the patients rated the events as being severe.
These events appeared to be dose related. Table 1 lists signs and symptoms that were reported in greater than 2% of patients in three multiple dose, placebo-controlled studies who received tizanidine where the frequency in the tizanidine group was greater than the placebo group. For comparison purposes, the corresponding frequency of the event (per 100 patients) among placebo treated patients is also provided.
Table 1: Multiple Dose, Placebo-Controlled Studies—Frequent (>2%) Adverse Reactions Reported for Which Tizanidine Tablets Incidence is Greater than Placebo Event Placebo N = 261 % Tizanidine Tablet N = 264 % Dry mouth 10 49 Somnolence 10 48 Asthenia* 16 41 Dizziness 4 16 UTI 7 10 Infection 5 6 Constipation 1 4 Liver test abnormality 2 6 Vomiting 0 3 Speech disorder 0 3 Amblyopia (blurred vision) <1 3 Urinary frequency 2 3 Flu symptom 2 3 Dyskinesia 0 3 Nervousness <1 3 Pharyngitis 1 3 Rhinitis 2 3 *(weakness, fatigue, and/or tiredness) In the single dose, placebo-controlled study involving 142 patients with spasticity due to multiple sclerosis (Study 1) [see Clinical Studies (14)], the patients were specifically asked if they had experienced any of the four most common adverse reactions: dry mouth, somnolence (drowsiness), asthenia (weakness, fatigue and/or tiredness) and dizziness.
In addition, hypotension and bradycardia were observed. The occurrence of these reactions is summarized in Table 2. Other events were, in general, reported at a rate of 2% or less.
Table 2: Single Dose, Placebo-Controlled Study—Common Adverse Reactions Reported Event Placebo N = 48 % Tizanidine Tablet,8 mg, N = 45 % Tizanidine Tablet,16 mg, N = 49 % Somnolence 31 78 92 Dry mouth 35 76 88 Asthenia* 40 67 78 Dizziness 4 22 45 Hypotension 0 16 33 Bradycardia 0 2 10 *(weakness, fatigue, and/or tiredness)
6.2Postmarketing Experience The following adverse reactions have been identified during post approval use of tizanidine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Certain events, such as somnol…
🔄 Drug Interactions ▾
7. Drug Interactions
7.1Fluvoxamine Concomitant use of fluvoxamine and tizanidine is contraindicated. Changes in pharmacokinetics of tizanidine when administered with fluvoxamine resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment. [see Contraindications (4) and Clinical Pharmacology (12.3)]
7.2Ciprofloxacin Concomitant use of ciprofoxacin and tizanidine is contraindicated. Changes in pharmacokinetics of tizanidine when administered with ciprofloxacin resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [see Contraindications (4) and Clinical Pharmacology (12.3)]
7.3CYP1A2 Inhibitors other than Fluvoxamine and Ciprofloxacin Because of potential drug interactions, concomitant use of tizanidine with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than strong CYP1A2 inhibitors (which are contraindicated), antiarrythmics (amiodarone, mexiletine, propafenone, and verapamil), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided. If their use is clinically necessary, therapy should be initiated with 2 mg dose and increased in 2–4 mg steps daily based on patient response to therapy.
If adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce or discontinue tizanidine therapy. [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]
7.4Oral Contraceptives Concomitant use of tizanidine with oral contraceptives is not recommended. However, if concomitant use is clinically necessary, initiate tizanidine with a single 2 mg dose and increase in 2–4 mg steps daily based on patient response to therapy. If adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce or discontinue tizanidine therapy. [see Clinical Pharmacology (12.3)]
7.5Alcohol Alcohol increases the overall amount of drug in the bloodstream after a dose of tizanidine. This was associated with an increase in adverse reactions of tizanidine. The CNS depressant effects of tizanidine and alcohol are additive. [see Clinical Pharmacology (12.3)]
7.6Other CNS Depressants The sedative effects of tizanidine with CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive. Monitor patients who take tizanidine with another CNS depressant for symptoms of excess sedation. [see Clinical Pharmacology (12.3)] 7.7 a2-adrenergic agonists Because hypotensive effects may be cumulative, it is not recommended that tizanidine be used with other α2-adrenergic agonists. [see Warnings and Precautions (5.1)]
👥 Use in Specific Populations ▾
8. Use in Specific Populations
8.1Pregnancy Pregnancy Category C Tizanidine has not been studied in pregnant women. Tizanidine should be given to pregnant women only if the benefit outweighs the risk to the unborn fetus. Reproduction studies performed in rats at a dose of 3 mg/kg, equal to the maximum recommended human dose on a mg/m2 basis, and in rabbits at 30 mg/kg, 16 times the maximum recommended human dose on a mg/m2 basis, did not show evidence of teratogenicity.
Tizanidine at doses that are equal to and up to 8 times the maximum recommended human dose on a mg/m2 basis increased gestation duration in rats. Prenatal and postnatal pup loss was increased and developmental retardation occurred. Post-implantation loss was increased in rabbits at doses of 1 mg/kg or greater, equal to or greater than 0.5 times the maximum recommended human dose on a mg/m2 basis.
8.3Nursing mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when tizanidine is administered to a nursing woman.
8.4Pediatric use Safety and effectiveness in pediatric patients have not been established.
8.5Geriatric use Tizanidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Clinical studies of tizanidine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects.
Cross-study comparison of pharmacokinetic data following single dose administration of 6 mg tizanidine showed that younger subjects cleared the drug four times faster than the elderly subjects. In elderly patients with renal insufficiency (creatinine clearance <25 mL/min), tizanidine clearance is reduced by more than 50% compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. During titration, the individual doses should be reduced.
If higher doses are required, individual doses rather than dosing frequency should be increased. Monitor elderly patients because they may have an increased risk for adverse reactions associated with tizanidine.
8.6Impaired Renal Function Tizanidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. In patients with renal insufficiency (creatinine clearance < 25 mL/min) clearance was reduced by more than 50%. In these patients, during titration, the individual doses should be reduced.
If higher doses are required, individual doses rather than dosing frequency should be increased. These patients should be monitored closely for the onset or increase in severity of the common adverse events (dry mouth, somnolence, asthenia and dizziness) as indicators of potential overdose. [see Dosage and Administration (2.2), Warnings and Precautions (5.7) and Clinical Pharmacology (12.3)]
8.7Impaired Hepatic Function The influence of hepatic impairment on the pharmacokinetics of tizanidine has not been evaluated. Because tizanidine is extensively metabolized in the liver, hepatic impairment would be expected to have significant effects on pharmacokinetics of tizanidine. [see Dosing and Administration (2.3), Warnings and Precautions (5.2), and Clinical Pharmacology (12.3)].
🆘 Overdosage ▾
10. Overdosage 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, basic steps to ensure the adequacy of an airway and the monitoring of cardiovascular and respiratory systems should be undertaken. Tizanidine is a lipid-soluble drug, which is only slightly soluble in water and methanol.
Therefore, dialysis is not likely to be an efficient method of removing drug from the body. In general, symptoms resolve within one to three days following discontinuation of tizanidine and administration of appropriate therapy. Due to the similar mechanism of action, symptoms and management of tizanidine overdose are similar to that following clonidine overdose.
For the most recent information concerning the management of overdose, contact a poison control center.
🧬 Clinical Pharmacology ▾
12. Clinical Pharmacology
12.1Mechanism of action Tizanidine is a central alpha-2-adrenergic receptor agonist and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. The effects of tizanidine are greatest on polysynaptic pathways. The overall effect of these actions is thought to reduce facilitation of spinal motor neurons.
12.3Pharmacokinetics Absorption and Distribution Following oral administration, tizanidine is essentially completely absorbed. The absolute oral bioavailability of tizanidine is approximately 40% (CV = 24%), due to extensive first-pass hepatic metabolism. Tizanidine is extensively distributed throughout the body with a mean steady state volume of distribution of
2.4L/kg (CV = 21%) following intravenous administration in healthy adult volunteers. Tizanidine is approximately 30% bound to plasma proteins. Differences between tizanidine capsules and tizanidine tablets Tizanidine capsules and tizanidine tablets are bioequivalent to each other under fasting conditions, but not under fed conditions.
A single dose of either two 4 mg tablets or two 4 mg capsules was administered under fed and fasting conditions in an open label, four period, randomized crossover study in 96 human volunteers, of whom 81 were eligible for the statistical analysis. Following oral administration of either the tablet or capsule (in the fasted state), peak plasma concentrations of tizanidine occurred 1.0 hours after dosing with a half-life of approximately 2 hours. When two 4 mg tablets were administered with food, the mean maximal plasma concentration was increased by approximately 30%, and the median time to peak plasma concentration was increased by 25 minutes, to 1 hour and 25 minutes.
In contrast, when two 4 mg capsules were administered with food, the mean maximal plasma concentration was decreased by 20%, the median time to peak plasma concentration was increased 2 to 3 hours. Consequently, the mean Cmax for the capsule when administered with food is approximately 66% the Cmax for the tablet when administered with food. Food also increased the extent of absorption for both the tablets and capsules.
The increase with the tablet (~30%) was significantly greater than with the capsule (~10%). Consequently when each was administered with food, the amount absorbed from the capsule was about 80% of the amount absorbed from the tablet. Administration of the capsule contents sprinkled on applesauce was not bioequivalent to administration of an intact capsule under fasting conditions.
Administration of the capsule contents on applesauce resulted in a 15%–20% increase in Cmax and AUC of tizanidine and a 15 minute decrease in the median lag time and time to peak concentration compared to administration of an intact capsule while fasting. Figure 1: Mean Tizanidine Concentration vs. Time Profiles For Tizanidine Tablets and Capsules (2 × 4 mg) Under Fasted and Fed Conditions Metabolism and Excretion Tizanidine has linear pharmacokinetics over the doses studied in clinical development (1–20 mg).
Tizanidine has a half-life of approximately 2.5 hours (CV=33%). Approximately 95% of an administered dose is metabolized. The primary cytochrome P450 isoenzyme involved in tizanidine metabolism is CYP1A2.
Tizanidine metabolites are not known to be active; their half-lives range from 20 to 40 hours. Following single and multiple oral dosing of 14C-tizanidine, an average of 60% and 20% of total radioactivity was recovered in the urine and feces, respectively. Special Populations Age Effects No specific pharmacokinetic study was conducted to investigate age effects.
Cross study comparison of pharmacokinetic data following single dose administration of 6 mg tizanidine showed that younger subjects cleared the drug four times faster than the elderly subjects. Tizanidine has not been evaluated in children. [see Use in Specific Populations (8.4, 8.5)] Hepatic Impairment The influence of hepatic impairment on the pharmacokinetics…
📦 How Supplied / Storage and Handling ▾
16. How Supplied/Storage and Handling Tizanidine tablets USP, 2 mg are debossed with "U" and "168" on one side and bisecting score on other side. Bottles of 30 Tablets NDC: 80425-0187-01 Bottles of 60 Tablets NDC: 80425-0187-02 Bottles of 90 Tablets NDC: 80425-0187-03 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in tight, light-resistant container [see USP].
📋 Description ▾
11. Description Tizanidine hydrochloride is a central alpha2-adrenergic agonist. Tizanidine hydrochloride, USP is a white to off-white, fine crystalline powder, which is odorless or with a faint characteristic odor.
Tizanidine is slightly soluble in water and methanol; solubility in water decreases as the pH increases. Its chemical name is 5-chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiadiazole monohydrochloride. Tizanidine's molecular formula is C9H8ClN5S-HCl, its molecular weight is 290.2 and its structural formula is: Tizanidine tablets, USP are supplied as 2 mg and 4 mg tablets for oral administration.
Tizanidine tablets, USP contain the active ingredient, tizanidine hydrochloride (2.288 mg equivalent to 2 mg tizanidine base and 4.576 mg equivalent to 4 mg tizanidine base), and the inactive ingredients, colloidal silicon dioxide, stearic acid, microcrystalline cellulose and anhydrous lactose. Structure