TIZANIDINE HYDROCHLORIDE 4 mg Capsule, 30-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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💊 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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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.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 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 | $0.3010 | $9.03 / 30 capsules |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| tizanidine hydrochloride 4 mg 00591-2789-86 | Actavis | 150 capsules | $0.088 | AB | Availability likely | — |
| Tizanidine Hydrochloride 4 mg 50742-0225-15 | Ingenus | 150 capsules | $0.088 | AB | Availability likely | — |
| Tizanidine Hydrochloride 4 mg 59651-0315-77 | Aurobindo | 150 capsules | $0.088 | — | Availability likely | — |
| tizanidine hydrochloride 4 mg 72888-0002-15 | Advagen | 150 capsules | $0.088 | — | Availability likely | — |
| Tizanidine Hydrochloride 4 mg 75834-0208-15 | Nivagen | 150 capsules | $0.163 | AB | Discontinued | — |
| Tizanidine Hydrochloride 4 mg 42291-0811-15 | AvKARE | 150 capsules | — | AB | FDA listed | — |
| Tizanidine Hydrochloride 4 mg 46708-0492-08 | Alembic | 640 capsules | — | AB | FDA listed | — |
| Tizanidine Hydrochloride 4 mg 60505-2649-03 | Apotex | 30 capsules | — | AB | FDA listed | — |
| Tizanidine Hydrochloride 4 mg 62332-0492-08 | Alembic | 640 capsules | — | AB | FDA listed | — |
| Tizanidne hydrochloride 4 mg 63629-8872-01 | Bryant | 150 capsules | — | AB | FDA listed | — |
| Tizanidne hydrochloride 4 mg 67877-0611-05 | Ascend | 500 capsules | — | AB | FDA listed | — |
| Tizanidine Hydrochloride 4 mgthis 68788-8747-03 | Preferred | 30 capsules | — | AB | FDA listed | — |
| tizanidine hydrochloride 4 mg 68788-8776-01 | Preferred | 100 capsules | — | — | FDA listed | — |
| Tizanidne hydrochloride 4 mg 68788-8798-01 | Preferred | 100 capsules | — | AB | FDA listed | — |
| Zanaflex 4 mg 70515-0604-15 | Covis | 150 capsules | — | AB | FDA listed | — |
| tizanidine hydrochloride 4 mg 70710-1112-04 | Zydus | 100 capsules | — | AB | FDA listed | — |
| tizanidine hydrochloride 4 mg 70771-1068-04 | Zydus | 100 capsules | — | AB | FDA listed | — |
| Tizanidine hydrochloride 4 mg 71209-0065-07 | Cadila | 150 capsules | — | AB | FDA listed | — |
| Tizanidne hydrochloride 4 mg 71335-2209-01 | Bryant | 150 capsules | — | AB | FDA listed | — |
| tizanidine hydrochloride 4 mg 71335-2559-01 | Bryant | 1 capsule | — | — | FDA listed | — |
| Tizanidne hydrochloride 4 mg 72162-1861-02 | Bryant | 150 capsules | — | AB | FDA listed | — |
| Tizanidine hydrochloride 4 mg 72241-0042-07 | Modavar | 150 capsules | — | AB | FDA listed | — |
| tizanidine hydrochloride 4 mg 72789-0507-77 | PD-Rx | 150 capsules | — | — | FDA listed | — |
| Tizanidine Hydrochloride 4 mg 76420-0901-01 | Asclemed | 10 capsules | — | AB | FDA listed | — |
| Tizanidine HCL 4 mg 80425-0090-01 | Advanced | 60 capsules | — | AB | FDA listed | — |
| Tizanidine HCL 4 mg 80425-0144-01 | Advanced | 30 capsules | — | AB | FDA listed | — |
| tizanidine hydrochloride 4 mg 80425-0474-01 | Advanced | 30 capsules | — | — | FDA listed | — |
| Zanaflex 4 mg 83107-0002-15 | Legacy | 150 capsules | — | AB | FDA listed | — |
| Tizanidine hydrochloride 4 mg 85742-0032-30 | Kanchan | 150 capsules | — | AB | 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
Age at onset
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 68788-8747-01 | 100 CAPSULE in 1 BOTTLE, PLASTIC (68788-8747-1) | 2024-09-26 | Active |
| 68788-8747-02 | 20 CAPSULE in 1 BOTTLE, PLASTIC (68788-8747-2) | 2024-09-26 | Active |
| 68788-8747-03 You're viewing this | 30 CAPSULE in 1 BOTTLE, PLASTIC (68788-8747-3) | 2024-09-26 | Active |
| 68788-8747-06 | 60 CAPSULE in 1 BOTTLE, PLASTIC (68788-8747-6) | 2024-09-26 | Active |
| 68788-8747-08 | 120 CAPSULE in 1 BOTTLE, PLASTIC (68788-8747-8) | 2024-09-26 | Active |
| 68788-8747-09 | 90 CAPSULE in 1 BOTTLE, PLASTIC (68788-8747-9) | 2024-09-26 | Active |
You're viewing one of 6 pack sizes for this product.
Pack size FAQ
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🧭 About this NDC listing & data coverage
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| 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 Tizanidine hydrochloride is 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 ] . 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 capsules should be reserved for those daily activities and times when relief of spasticity is most important
⏱️ 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 • 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 • 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 • To discontinue tizanidine, decrease dose slowly to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia
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 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 ]. The recommended starting dose is 2 mg. Because the effect of tizanidine hydrochloride capsules 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 capsules 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 ] .
2.3Dosing in Patients with Hepatic Impairment Tizanidine hydrochloride capsules 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 ].
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 ].
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Capsules 2 mg: Hard gelatin size "4" capsule, with light blue opaque body and cap, imprinted 'ING 224' with black ink on both the cap and body filled with white to off-white granular powder 4 mg: Hard gelatin size "3" capsule, with white opaque body and light blue opaque cap, imprinted 'ING 225' with black ink on both the cap and body filled with white to off-white granular powder 6 mg: Hard gelatin size "2" capsule, with blue opaque body and cap, imprinted 'ING 226' with black ink on both the cap and body filled with white to off-white granular powder • Capsules: 2 mg, 4 mg or 6 mg ()
⛔ Contraindications ▾
4 CONTRAINDICATIONS Tizanidine hydrochloride capsules are contraindicated in patients taking potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin [see ]. • Concomitant use with potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin (, )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; Tizanidine hydrochloride capsules should not be used with other α 2 -adrenergic agonists (,) • Risk of liver injury: monitor ALTs; discontinue tizanidine if liver injury occurs () • Sedation: tizanidine may interfere with everyday activities; sedative effects of tizanidine, alcohol, and other CNS depressants are additive (, ,) • Hallucinations: consider discontinuation of tizanidine () • Less potent inhibitors of CYP1A2: may cause hypotension, bradycardia, or excessive drowsiness, use caution if tizanidine is used with less potent inhibitors of CYP1A2, e.g., zileuton, other fluoroquinolones, antiarrhythmics, cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine (,, ) • Renal impairment (creatinine clearance <25 mL/min): use tizanidine with caution, and monitor closely for dry mouth, somnolence, asthenia and dizziness as indicators of potential overdose ()
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 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 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 and , ] .
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 and ] .
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 ].
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), antiarrhythmics (amiodarone, mexiletine, propafenone), cimetidine, famotidine, oral contraceptives, acyclovir, an…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in other sections of the prescribing information: • Hypotension [ )] • Liver Injury [ ] • Sedation [ ] • Hallucinosis/Psychotic-Like Symptoms [ ] • Hypersensitivity Reactions [ ] 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 () To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals, LLC at 1-877-748-1970 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 to 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 *(weakness, fatigue, and/or tiredness) 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 syndrome 2 3 Dyskinesia 0 3 Nervousness <1 3 Pharyngitis 1 3 Rhinitis 2 3 In the single dose, placebo-controlled study involving 142 patients with spasticity due to multiple sclerosis (Study 1) [see )], 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 * (weakness, fatigue, and/or tiredness) Event Placebo N = 48 % Tizanidine Tablet, 8mg, N = 45 % Tizanidine Tablet, 16 mg, N = 49 % Somnolence 31 78 92 Dry mouth 35 76 88 Asth…
🔄 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 ].
7.2Ciprofloxacin Concomitant use of ciprofloxacin 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 and ].
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), 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 to 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 and ].
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 to 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 ].
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. The CNS depressant effects of tizanidine and alcohol are additive [see ].
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 ].
7.7Alpha2 -Adrenergic Agonists Because hypotensive effects may be cumulative, it is not recommended that tizanidine be used with other α2-adrenergic agonists [see ].
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Pregnancy: Based on animal data, may cause fetal harm () • Geriatric use: Tizanidine should be used with caution in elderly patients because clearance is decreased four-fold ()
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of tizanidine 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/m 2 ) 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/m 2 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/m 2 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 and any potential adverse effects on the breastfed infant from tizanidine 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 on female or male reproductive potential. Oral administration of tizanidine to male and female rats resulted in adverse effects on fertility [see ].
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), tiz…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of tizanidine 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/m 2 ) 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/m 2 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/m 2 basis, respectively.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
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.
🆘 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 Hydrochloride Capsules and Tizanidine Tablets Tizanidine hydrochloride 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 to 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 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 i…
🧬 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 Hydrochloride 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. 4 mg capsules: Hard gelatin size "3" capsule, with white opaque body and light blue opaque cap, imprinted 'ING 225' with black ink on both the cap and body filled with white to off-white granular powder, in bottles of; 20 capsules NDC 68788-8747-2 30 capsules NDC 68788-8747-3 60 capsules NDC 68788-8747-6 90 capsules NDC 68788-8747-9 100 capsules NDC 68788-8747-1 120 capsules NDC 68788-8747-8 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 a tight, light resistant containers as defined in USP using child resistant closure.
📋 Description ▾
11 DESCRIPTION Tizanidine hydrochloride is a central alpha 2 -adrenergic agonist. Tizanidine hydrochloride, USP is a white to slightly yellow crystalline powder. Tizanidine is slightly soluble in water and methanol.
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, microcrystalline cellulose, anhydrous lactose, colloidal silicon dioxide, stearic acid.
In addition, each of the empty hard gelatin capsules contain the following: gelatin, titanium dioxide, sodium lauryl sulfate and FD&C blue #1. The imprinting ink contains the following: shellac, propylene glycol, potassium hydroxide, ammonia and black iron oxide. tizanidine structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Serious Drug Interactions Advise patients they should not take tizanidine hydrochloride capsules 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 capsules and other medicines. Tizanidine Hydrochloride Capsules 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 capsules 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 capsules, because rebound hypertension and tachycardia may occur. Effects of Tizanidine Hydrochloride Capsules 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 capsules 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 capsules 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 capsules decreases spasticity and caution should be used.
Manufactured for: Ingenus Pharmaceuticals, LLC Orlando, FL 32811 Rx Only 553902 Revised: 06/2023 Repackaged By Preferred Pharmaceuticals Inc. Image