tizanidine hydrochloride 2 mg Capsule, Gelatin Coated, 150-count
🆔 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 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...
Patient education
Supplement & herbal interactions
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Ask a licensed pharmacist directly — free, answered by our team.
💊 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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII H3R47K3TBD
FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
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UNII 2G86QN327L
Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
6 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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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 ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.083 | $12.38 / 150 capsules |
| Medicaid paysCMS SDUD · 12 mo | $0.2952 | $44.28 / 150 capsules |
| Medicare drug plans payPart D · Q2 2026 | $0.3010 | $45.15 / 150 capsules |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| tizanidine hydrochloride 2 mgthis 00591-2788-86 | Actavis | 150 capsules | $0.082 | AB | Availability likely | — |
| Tizanidine Hydrochloride 2 mg 50742-0224-15 | Ingenus | 150 capsules | $0.082 | AB | Availability likely | — |
| Tizanidine Hydrochloride 2 mg 59651-0314-77 | Aurobindo | 150 capsules | $0.082 | — | Availability likely | — |
| tizanidine hydrochloride 2 mg 72888-0001-15 | Advagen | 150 capsules | $0.082 | — | Availability likely | — |
| Tizanidine Hydrochloride 2 mg 75834-0207-15 | Nivagen | 150 capsules | $0.106 | AB | Discontinued | +28% |
| Tizanidine Hydrochloride 2 mg 46708-0491-08 | Alembic | 640 capsules | — | AB | FDA listed | — |
| Tizanidine Hydrochloride 2 mg 60505-2648-03 | Apotex | 30 capsules | — | AB | FDA listed | — |
| Tizanidine Hydrochloride 2 mg 62332-0491-08 | Alembic | 640 capsules | — | AB | FDA listed | — |
| Tizanidne hydrochloride 2 mg 63629-8871-01 | Bryant | 150 capsules | — | AB | FDA listed | — |
| Tizanidne hydrochloride 2 mg 67877-0610-05 | Ascend | 500 capsules | — | AB | FDA listed | — |
| Zanaflex 2 mg 70515-0602-15 | Covis | 150 capsules | — | AB | FDA listed | — |
| tizanidine hydrochloride 2 mg 70710-1111-04 | Zydus | 100 capsules | — | AB | FDA listed | — |
| tizanidine hydrochloride 2 mg 70771-1067-04 | Zydus | 100 capsules | — | AB | FDA listed | — |
| Tizanidine hydrochloride 2 mg 71209-0064-07 | Cadila | 150 capsules | — | AB | FDA listed | — |
| Tizanidne hydrochloride 2 mg 71335-2208-01 | Bryant | 150 capsules | — | AB | FDA listed | — |
| Tizanidne hydrochloride 2 mg 72162-1860-02 | Bryant | 150 capsules | — | AB | FDA listed | — |
| Tizanidine hydrochloride 2 mg 72241-0041-07 | Modavar | 150 capsules | — | AB | FDA listed | — |
| tizanidine hydrochloride 2 mg 72789-0506-77 | PD-Rx | 150 capsules | — | — | FDA listed | — |
| Tizanidine Hydrochloride 2 mg 76420-0900-01 | Asclemed | 10 capsules | — | AB | FDA listed | — |
| Zanaflex 2 mg 83107-0001-15 | Legacy | 150 capsules | — | AB | FDA listed | — |
| Tizanidine hydrochloride 2 mg 85742-0031-30 | Kanchan | 150 capsules | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Where does this data come from?
🗺️ Medicaid utilization & spend
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00591-2788-86 You're viewing this | 150 CAPSULE, GELATIN COATED in 1 BOTTLE, PLASTIC (0591-2788-86) | 2012-02-06 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Tizanidine hydrochloride capsules are indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine hydrochloride capsules should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration ( 2.1 )] . Tizanidine hydrochloride is a central alpha-2-adrenergic agonist indicated for the management of spasticity.
Because of the short duration of therapeutic effect, treatment with tizanidine hydrochloride should be reserved for those daily activities and times when relief of spasticity is most important. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended starting dose: 2 mg; dose can be repeated at 6 to 8 hour intervals, up to a maximum of 3 doses in 24 hours ( 2.1 ) Dosage can be increased by 2 mg to 4 mg per dose, with 1 to 4 days between increases; total daily dose should not exceed 36 mg ( 2.1 ) 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 ( 2.1 , 12.3 ) To discontinue tizanidine hydrochloride, decrease dose slowly to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia ( 2.2 )
2.1Dosing Information Tizanidine hydrochloride capsules 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 hydrochloride capsules and tizanidine hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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. 4 Drug 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 Capsules 2 mg: Light blue opaque body with a light blue opaque cap with “2 MG” printed on the cap 4 mg: White opaque body with a blue opaque cap with “4 MG” printed on the cap 6 mg: Blue opaque body with a white stripe and blue opaque cap with “6 MG” printed on the cap Capsules: 2 mg, 4 mg or 6 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Tizanidine hydrochloride is contraindicated in patients taking potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin [see Drug Interactions ( 7.1 , 7.2 )]. Concomitant use with potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin ( 4 , 5.5 , 7.1 , 7.2 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; tizanidine hydrochloride should not be used with other α 2 -adrenergic agonists ( 5.1 , 7.7 ) Risk of liver injury: monitor ALTs; discontinue tizanidine hydrochloride if liver injury occurs ( 5.2 ) Sedation: Tizanidine hydrochloride may interfere with everyday activities; sedative effects of tizanidine hydrochloride, alcohol, and other CNS depressants are additive ( 5.3 , 7.5 , 7.6 ) Hallucinations: consider discontinuation of tizanidine hydrochloride ( 5.4 ) Less potent inhibitors of CYP1A2: may cause hypotension, bradycardia, or excessive drowsiness, use caution if tizanidine hydrochloride is used with less potent inhibitors of CYP1A2, e.g., zileuton, other fluoroquinolones, antiarrhythmics , cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine ( 5.5 , 7.3 , 12.3 ) Renal impairment (creatinine clearance < 25 mL/min): use tizanidine hydrochloride with caution, and monitor closely for dry mouth, somnolence, asthenia and dizziness as indicators of potential overdose ( 5.7 )
5.1Hypotension Tizanidine is an α 2 -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 hydrochloride is used in patients receiving concurrent antihypertensive therapy. It is not recommended that tizanidine hydrochloride 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 either fluvoxamine or ciprofloxacin and single doses of 4 mg of tizanidine hydrochloride. Therefore, concomitant use of tizanidine hydrochloride 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 hydrochloride may cause hepatocellular liver injury. Tizanidine hydrochloride 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 hydrochloride 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 hydrochloride with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive.
Monitor patients who take tizanidine hydrochloride with another CNS depressant for symptoms of excess sedation. [ s ee Drug Interactions ( 7.5 , 7.6 )]
5.4Hallucinosis/Psychotic-Like Symptoms Tizanidine hydrochloride 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 hydrochloride in patients who develop hallucinations.
5.5Interaction with CYP1A2 Inhibitors Because of potential drug interactions, tizanidine hydrochloride is…
🤒 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 )] The most common adverse reactions (greater than 2% of 264 patients taking tizanidine and greater than in placebo-treated patients in three multiple dose, placebo-controlled studies) were dry mouth, somnolence, asthenia, dizziness, urinary tract infection, constipation, liver function tests abnormal, vomiting, speech disorder, amblyopia, urinary frequency, flu syndrome, SGPT/ALT increased, dyskinesia, nervousness, pharyngitis, and rhinitis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA,Inc. at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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 hydrochloride where the frequency in the tizanidine hydrochloride 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 Hydrochloride Tablets Incidence is Greater than Placebo Event Placebo N = 261 % Tizanidine H ydrochloride 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 syndrome 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: Singl…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Fluvoxamine Concomitant use of fluvoxamine and tizanidine hydrochloride is contraindicated. Changes in pharmacokinetics of tizanidine when administered with fluvoxamine resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [ s ee Contraindications ( 4 ) and Clinical Pharmacology ( 12.3 )].
7.2Ciprofloxacin Concomitant use of ciprofoxacin and tizanidine hydrochloride is contraindicated. Changes in pharmacokinetics of tizanidine when administered with ciprofloxacin resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [s ee Contraindications ( 4 ) and Clinical Pharmacology ( 12.3 )].
7.3CYP1A2 Inhibitors other than Fluvoxamine and Ciprofloxacin Because of potential drug interactions, concomitant use of tizanidine hydrochloride with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than strong CYP1A2 inhibitors (which are contraindicated), antiarrhythmics (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 [ s ee Warnings and Precautions ( 5.5 ) and Clinical Pharmacology ( 12.3 )].
7.4Oral Contraceptives Concomitant use of tizanidine hydrochloride with oral contraceptives is not recommended. However, if concomitant use is clinically necessary, initiate tizanidine hydrochloride 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 [ s ee Clinical Pharmacology ( 12.3 )].
7.5Alcohol Alcohol increases the overall amount of drug in the bloodstream after a dose of tizanidine hydrochloride. This was associated with an increase in adverse reactions of tizanidine hydrochloride. The CNS depressant effects of tizanidine hydrochloride and alcohol are additive [ s ee Clinical Pharmacology ( 12.3 )].
7.6Other CNS Depressants The sedative effects of tizanidine hydrochloride with CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive. Monitor patients who take tizanidine hydrochloride with another CNS depressant for symptoms of excess sedation [ s ee Clinical Pharmacology ( 12.3 )]. 7.7 α 2 -Adrenergic A gonists Because hypotensive effects may be cumulative, it is not recommended that tizanidine hydrochloride be used with other α 2 -adrenergic agonists [ s ee Warnings and Precautions ( 5.1 )].
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) Geriatric use: Tizanidine hydrochloride should be used with caution in elderly patients because clearance is decreased four-fold ( 8.5 )
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of tizanidine hydrochloride 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% - 4% and 15% - 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/m2) basis. Oral administration of tizanidine (1 to 100 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in embryofetal and postnatal offspring mortality at all doses. Maternal toxicity was observed at the highest dose tested.
Oral administration of tizanidine (10 and 30 mg/kg/day) during the perinatal period of pregnancy (2-6 days prior to delivery) resulted in increased postnatal offspring mortality at both doses. A no-effect dose for embryofetal developmental toxicity in rabbit was not identified. The lowest dose tested (1 mg/kg/day) is less than the MRHD on a mg/m2 basis.
In a pre- and postnatal development study in rats, oral administration of tizanidine (3 to 30 mg/kg/day) resulted in increased postnatal offspring mortality. A no-effect dose for pre- and postnatal developmental toxicity was not identified. The lowest dose tested (3 mg/kg/day) is similar to the MRHD on a mg/m2 basis, respectively.
8.2Lactation Risk Summary There are no data on the presence of tizanidine in human milk, the effects on the breastfed infant, or the effects on human milk production. Animal studies have reported the presence of tizanidine in the milk of lactating animals. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tizanidine hydrochloride and any potential adverse effects on the breastfed infant from tizanidine hydrochloride or from the underlying maternal condition.
8.3Females and Males of Reproductive Potential There are no adequate and well-controlled studies in humans on the effect of tizanidine hydrochloride on female or male reproductive potential. Oral administration of tizanidine to male and female rats resulted in adverse effects on fertility [see Nonclinical Toxicology ( 13.1 )].
8.4Pediatric U se Safety and effectiveness in pediatric patients have not been established.
8.5Geriatric U se Tizanidine hydrochloride 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 hydrochloride 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 hydrochloride showed that younger subject…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of tizanidine hydrochloride 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% - 4% and 15% - 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/m2) basis. Oral administration of tizanidine (1 to 100 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in embryofetal and postnatal offspring mortality at all doses. Maternal toxicity was observed at the highest dose tested.
Oral administration of tizanidine (10 and 30 mg/kg/day) during the perinatal period of pregnancy (2-6 days prior to delivery) resulted in increased postnatal offspring mortality at both doses. A no-effect dose for embryofetal developmental toxicity in rabbit was not identified. The lowest dose tested (1 mg/kg/day) is less than the MRHD on a mg/m2 basis.
In a pre- and postnatal development study in rats, oral administration of tizanidine (3 to 30 mg/kg/day) resulted in increased postnatal offspring mortality. A no-effect dose for pre- and postnatal developmental toxicity was not identified. The lowest dose tested (3 mg/kg/day) is similar to the MRHD on a mg/m2 basis, respectively.
🧒 Pediatric Use ▾
8.4Pediatric U se Safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric U se Tizanidine hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride.
🆘 Overdosage ▾
10 OVERDOSAGE A review of the safety surveillance database revealed cases of intentional and accidental tizanidine hydrochloride 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 Hydrochloride Capsules and Tizanidine Hydrochloride Tablets Tizanidine hydrochloride capsules and tizanidine hydrochloride 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 C max for the capsule when administered with food is approximately 66% the C max 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 C max 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 Hydrochloride 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 14 C-tizanidine, an average of 60% and 20% of total radioactivity was recovered in the urine and feces, respectively. Specific 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 hydrochloride showed that younger subjects cleared the drug four times faster than the elderly subjects. Tizanidine hydrochloride has not been evaluated in children [ s ee Use in Specifi…
🧬 Mechanism of Action ▾
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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1Tizanidine H ydrochloride Capsules Tizanidine hydrochloride capsules are available in three strengths as two-piece hard gelatin capsules containing tizanidine hydrochloride 2.29 mg, 4.58 mg and 6.87 mg, equivalent to 2 mg, 4 mg and 6 mg tizanidine base. • The 2 mg capsules have a light blue opaque body with a light blue opaque cap with “2 MG” printed on the cap: bottles of 150 capsules (NDC 0591-2788-86) • The 4 mg capsules have a white opaque body with a blue opaque cap with “4 MG” printed on the cap: bottles of 150 capsules (NDC 0591-2789-86) • The 6 mg capsules have a blue opaque body with a white stripe and blue opaque cap with “6 MG” printed on the capsules: bottles of 150 capsules (NDC 0591-2790-86) Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Dispense in containers with child resistant closure.
📋 Description ▾
11 DESCRIPTION Tizanidine hydrochloride is a central alpha 2 -adrenergic agonist. Tizanidine HCl 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 C 9 H 8 ClN 5 S-HCl, its molecular weight is 290.2 and its structural formula is: Tizanidine hydrochloride capsules are supplied as 2, 4, and 6 mg capsules for oral administration. Tizanidine hydrochloride capsules contain the active ingredient, tizanidine hydrochloride (2.29 mg equivalent to 2 mg tizanidine base, 4.58 mg equivalent to 4 mg tizanidine base, and 6.87 mg equivalent to 6 mg tizanidine base), and the inactive ingredients, hypromellose, silicon dioxide, sugar spheres, titanium dioxide, gelatin, and colorants.
Structural formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Serious Drug Interactions Advise patients they should not take tizanidine hydrochloride if they are taking fluvoxamine or ciprofloxacin because of the increased risk of serious adverse reactions including severe lowering of blood pressure and sedation. Instruct patients to inform their physicians or pharmacists when they start or stop taking any medication because of the risks associated with interaction between tizanidine hydrochloride and other medicines. Tizanidine H ydrochloride Dosing Tell patients to take tizanidine hydrochloride capsules exactly as prescribed (consistently either with or without food) and not to switch between tablets and capsules.
Inform patients that they should not take more tizanidine hydrochloride than prescribed because of the risk of adverse events at single doses greater than 8 mg or total daily doses greater than 36 mg. Tell patients that they should not suddenly discontinue tizanidine hydrochloride, because rebound hypertension and tachycardia may occur. Effects of T izanidine H ydrochloride Warn patients that they may experience hypotension and to be careful when changing from a lying or sitting to a standing position.
Tell patients that tizanidine hydrochloride may cause them to become sedated or somnolent and they should be careful when performing activities that require alertness, such as driving a vehicle or operating machinery. Tell patients that the sedation may be additive when tizanidine hydrochloride is taken in conjunction with drugs (baclofen, benzodiazepines) or substances (e.g., alcohol) that act as CNS depressants. Remind patients that if they depend on their spasticity to sustain posture and balance in locomotion, or whenever spasticity is utilized to obtain increased function, that tizanidine hydrochloride decreases spasticity and caution should be used.
Manufactured for: Teva Pharmaceuticals USA, Inc. Parsippany, NJ 07054 Revised: February 2021