tizanidine 4 mg Tablet, 100-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
Some supplements/herbs that may interact with Tizanidine — tap one for details:
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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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UNII 3SY5LH9PMK
Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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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 4ELV7Z65AP
Stearic acid is a fatty acid derived from plant or animal sources. It acts as a binder and lubricant in tablets and capsules, helping them hold together and flow smoothly during manufacturing.
4 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 | $0.032 | $3.19 / 100 tablet |
| Medicaid paysCMS SDUD · 12 mo | $0.4733 | $47.33 / 100 tablet |
| Medicare drug plans payPart D · Q2 2026 | $0.1130 | $11.30 / 100 tablet |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| tizanidine 4 mgthis 00904-6418-61 | Major | 100 tablets | $0.032 | AB | Availability likely | — |
| Tizanidine 4 mg 16714-0172-01 | NorthStar | 150 tablets | $0.032 | AB | Availability likely | — |
| Tizanidine 4 mg 29300-0169-03 | Unichem | 300 tablets | $0.032 | AB | Availability likely | — |
| Tizanidine 4 mg 50268-0760-15 | AvPAK | 50 tablets | $0.032 | AB | Availability likely | — |
| Tizanidine 4 mg 57664-0503-18 | Sun | 1000 tablets | $0.032 | AB | Availability likely | — |
| Tizanidine 4 mg 68084-0645-01 | American | 100 tablets | $0.032 | AB | Availability likely | — |
| tizanidine 4 mg 00615-8469-39 | NCS | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 43063-0455-15 | PD-Rx | 15 tablets | — | AB | FDA listed | — |
| Tizanidine Hydrochloride 4 mg 49999-0347-01 | Quality | 120 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 50090-0840-00 | A-S | 120 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 50090-5767-00 | A-S | 120 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 50090-6756-00 | A-S | 120 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 50090-6757-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 50090-7889-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 51655-0603-20 | Northwind | 20 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 51655-0740-26 | Northwind | 90 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 55111-0180-03 | Dr. | 300 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 55154-7287-00 | Cardinal | 10 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 60505-0252-01 | Apotex | 100 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 60760-0505-04 | St. | 4 tablets | — | AB | FDA listed | — |
| Tizanidine Hydrochloride 4 mg 61919-0196-30 | TIZANIDINE | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 63187-0009-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 63187-0145-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 63187-0493-15 | Proficient | 15 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 63187-0673-14 | Proficient | 14 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 63629-1673-00 | Bryant | 112 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 63629-2371-01 | Bryant | 1000 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 64980-0659-03 | Rising | 30 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 67046-1444-03 | Coupler | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 67296-2263-02 | Redpharm | 15 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 67877-0614-05 | Ascend | 500 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 68071-3719-03 | NuCare | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 68071-4463-03 | NuCare | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 68071-5268-03 | NuCare | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 68788-7781-01 | Preferred | 100 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 68788-8741-01 | Preferred | 100 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 68788-8802-01 | Preferred | 100 tablets | — | AB | FDA listed | — |
| Zanaflex 4 mg 70515-0594-15 | Covis | 150 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 70518-0133-00 | REMEDYREPACK | 60 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 70518-1598-01 | REMEDYREPACK | 60 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 70518-3658-00 | REMEDYREPACK | 30 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 70518-4181-00 | REMEDYREPACK | 90 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 70771-1336-00 | Zydus | 1000 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 71335-0914-00 | Bryant | 112 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 71335-1016-00 | Bryant | 112 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 71335-2325-00 | Bryant | 112 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 71335-3016-01 | Bryant | 90 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 71610-0228-30 | Aphena | 30 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 71610-0776-16 | Aphena | 6000 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 71610-0864-16 | Aphena | 6000 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 72162-1642-00 | Bryant | 1000 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 72189-0602-30 | Direct_rx | 30 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 72578-0097-06 | Viona | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 72789-0325-30 | PD-Rx | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 72789-0327-20 | PD-Rx | 20 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 76420-0229-30 | Asclemed | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 76420-0339-00 | Asclemed | 1000 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 76420-0866-00 | Asclemed | 1000 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 76420-0886-00 | Asclemed | 1000 tablets | — | AB | FDA listed | — |
| Tizanidine HCL 4 mg 80425-0022-01 | Advanced | 60 tablets | — | AB | FDA listed | — |
| Tizanidine HCl 4 mg 80425-0023-01 | Advanced | 60 tablets | — | AB | FDA listed | — |
| Tizanidine HCL 4 mg 80425-0024-01 | Advanced | 60 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 80425-0453-01 | Advanced | 30 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 80425-0454-01 | Advanced | 30 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 82461-0721-60 | Medcore | 60 tablets | — | AB | FDA listed | — |
| Zanaflex 4 mg 83107-0004-15 | Legacy | 150 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 85509-1180-01 | PHOENIX | 120 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 85534-0030-00 | HAWAII | 10 tablets | — | AB | FDA listed | — |
| tizanidine 4 mg 68788-4159-01 | Preferred | 100 tablets | — | AB | FDA listed | — |
| Tizanidine 4 mg 84386-0024-77 | 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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🗺️ Medicaid utilization & spend
🔬 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 |
|---|---|---|---|
| 00904-6418-61 You're viewing this | 100 BLISTER PACK in 1 CARTON (0904-6418-61) / 1 TABLET in 1 BLISTER PACK | 2014-10-01 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Tizanidine is indicated for the treatment of spasticity in adults. Tizanidine is a central alpha-2-adrenergic agonist indicated for the treatment of spasticity. (1)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved. ( 2.1 ) • Recommended starting dose: 2 mg by mouth every 6 to 8 hours, as needed, up to a maximum of 3 doses in 24 hours ( 2.2 ) • Dosage can be increased by 2 mg to 4 mg per dose every 1 to 4 days; maximum total daily dosage is 36 mg ( 2.2 ) • Tizanidine pharmacokinetics differs between tablets and capsules, and when taken with or without food. These differences could result in a change in tolerability and control of symptoms.
Consistent administration with respect to food is recommended. If substitution between dosage forms is necessary, take into consideration these pharmacokinetic differences. ( 2.2 , 2.6 , 12.3 ) • Patients with renal impairment (creatinine clearance <25 mL/min) or hepatic impairment: use lower individual doses during titration.If higher doses are required, individual doses rather than dosing frequency should be increased.
( 2.3 , 2.4 ) • To discontinue tizanidine tablets, decrease dose slowly to minimize the risk of withdrawal adverse reactions ( 2.5 )
2.1Recommended Evaluation and Testing Before and After Initiating Tizanidine Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved [see Warnings and Precautions ( 5.2 )].
2.2Recommended Dosage The recommended starting dose is 2 mg by mouth every 6 to 8 hours, as needed, to a maximum of three doses in 24 hours. Dosage can be gradually increased every 1 to 4 days by 2 mg to 4 mg at each dose based on clinical response and tolerability. The maximum total daily dosage is 36 mg.
Single doses greater than 16 mg have not been studied. There are pharmacokinetic differences when administering tizanidine between the fed or fasted state [see Clinical Pharmacology ( 12.3 )] . Tizanidine may be taken with or without food; however, consistent administration with respect to food is recommended to reduce variability in tizanidine plasma exposure.
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.
2.3Recommended Dosage in Patients with Renal Impairment I n patients with creatinine clearance < 25 mL/min, use lower individual doses during titration. If higher doses are required, the individual doses rather than dosing frequency should be increased [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )] .
2.4Recommended Dosage in Patients with Hepatic Impairment I n patients with hepatic impairment, use lower individual doses during titration. If higher doses are required, individual doses rather than dosing frequency should be increased [see Use in Specific Populations ( 8.7 ) and Clinical Pharmacology ( 12.3 )].
2.5Discontinuation of Tizanidine Tablets When discontinuing tizanidine tablets, particularly in patients who have been receiving high doses for long periods or who may be on concomitant treatment with narcotics, decrease the dosage by 2 mg to 4 mg per day to minimize the risk of withdrawal adverse reactions [see Drug Abuse and Dependence ( 9.3 )].
2.6Switching Between With/Without Food and Different Tizanidine Dosage Forms There are pharmacokinetic differences when: 1) switching between administration of tizanidine tablets with or without food 2) switching between dosage forms if being administered with food. If these situations occur, monitor patients for therapeutic effect or adverse reactions [see Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )].
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets 2 mg - white to off-white, round, scored tablets, imprinted “APO” over “TI-2” on one side and plain with a bisect score on the other side. 4 mg- white to off-white, round, scored tablets, imprinted “APO” over “TI-4” on one side and plain with a quadrisect score on the other side. • Tablets 2 mg and 4 mg (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Tizanidine is contraindicated in patients: • taking strong CYP1A2 inhibitors [see Drug Interactions ( 7.1 )]. • with a history of hypersensitivity to tizanidine or the ingredients in tizanidine tablets. Symptoms have included anaphylaxis and angioedema [see Warnings and Precautions ( 5.5 )]. • Concomitant use with strong CYP1A2 inhibitors ( 4 , 7.1 ) • Patients with a history of hypersensitivity to tizanidine or the ingredients in tizanidine tablets ( 4 , 5.5 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; tizanidine should not be used with other α 2 -adrenergic agonists ( 5.1 , 7.5 ) • Risk of liver injury: monitor ALTs; discontinue tizanidine if liver injury occurs ( 5.2 ) • Sedation: Tizanidine may interfere with everyday activities; sedative effects of tizanidine, alcohol, and other central nervous system (CNS) depressants are additive ( 5.3 , 7.4 ) • Hallucinations: consider discontinuation of tizanidine ( 5.4 )
5.1Hypotension Tizanidine is an α 2 -adrenergic agonist that can produce hypotension [see Adverse Reactions ( 6.1 ) and Drug Interactions ( 7.5 )] . Syncope has been reported in patients treated with tizanidine in the postmarketing setting. The risk of hypotension may be minimized by dose titration; monitoring for signs and symptoms of hypotension prior to dosage increase may minimize the risks associated with hypotension.
In addition, patients moving from a supine to fixed upright position may be at increased risk for hypotension and orthostatic effects. Monitor for hypotension when tizanidine is used in patients receiving concurrent antihypertensive therapy. It is not recommended that tizanidine be used with other α 2 -adrenergic agonists.Clinically significant hypotension (decreases in both systolic and diastolic pressure) has been reported with concomitant administration of tizanidine and strong CYP1A2 inhibitors [see Clinical Pharmacology ( 12.3 )] .
Therefore, concomitant use of tizanidine with strong CYP1A2 inhibitors is contraindicated [see Contraindications (4) and Drug Interactions ( 7.1 )].
5.2Liver Injury Tizanidine may cause hepatocellular liver injury. Liver function test abnormality and hepatotoxicity have been observed with tizanidine [seeAdverse Reactions ( 6.1 , 6.2 )]. Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected [see Dosage and Administration ( 2.1 ) and Use in Specific Populations ( 8.7 )] .
5.3Sedation Tizanidine can cause sedation, which may interfere with everyday activity. In the multiple dose studies of tizanidine, 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 [see Adverse Reactions ( 6.1 )]. The CNS depressant effects of tizanidine with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive [see Drug Interactions ( 7.4 )] .
Monitor patients who take tizanidine with another CNS depressant for symptoms of excess sedation.
5.4Hallucinosis / Psychotic-Like Symptoms Tizanidine use has been associated with hallucinations. Formed, visual hallucinations or delusions were 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. Hallucinations have also been reported with tizanidine use in the postmarketing setting.
Consider discontinuing tizanidine in patients who develop hallucinations.
5.5Hypersensitivity Reactions Tizanidine can cause anaphylaxis. Signs and symptoms of hypersensitivity, including respiratory compromise, urticaria, and angioedema of the throat and tongue, have been reported. Tizanidine is contraindicated in patients with a history of hypersensitivity reactions to tizanidine [see Contraindications ( 4 )].
5.6Withdrawal Adverse Reactions Tizanidine can cause withdrawal adverse reactions, which include rebound hypertension, tachycardia, and hypertonia. To minimize the risk of these reactions, particularly in patients who have been receiving high doses of tizanidine (20 to 28 mg daily)…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in other sections of the prescribing information: • Hypotension [see Warnings and Precautions ( 5.1 )] • Liver Injury [see Warnings and Precautions ( 5.2 )] • Sedation [see Warnings and Precautions ( 5.3 )] • Hallucinosis/Psychotic-Like Symptoms [see Warnings and Precautions ( 5.4 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] • Withdrawal Adverse Reactions [ see Warnings and Precautions ( 5.6 )] The most common adverse reactions (greater than 10% of patients taking tizanidine and greater than in patients taking placebo) were dry mouth, somnolence, asthenia, and dizziness.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical 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. The safety of tizanidine has been evaluated in three double-blind, randomized, placebo-controlled clinical studies [see Clinical Studies ( 14 )] . Two studies were conducted in patients with multiple sclerosis and one in patients with spinal cord injury.
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 period. In all, 264 patients received tizanidine and 261 patients received placebo. Across the three studies approximately 51% of patients were women, and the median dose during the plateau phase ranged from 20 to 28 mg/day.
The most common adverse reactions (>10% of patients treated with tizanidine) 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 reactions as mild to moderate and one-quarter of the patients rated the reactions as being severe. These adverse reactions appeared to be dose related.
Table 1 lists adverse reactions 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. Table 1: Multiple Dose, Placebo-Controlled Studies—Adverse Reactions Reported in >2% of Patients Treated with Tizanidine Tablets and Incidence Greater than Placebo Adverse Reaction 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 Liver test abnormality 2 6 Constipation 1 4 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 *includes 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 Adverse Reaction Placebo N = 48 % Tizanidine Tablet, 8mg, 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 *includ…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Moderate or weak CYP1A2 inhibitors: avoid concomitant use; may cause hypotension, bradycardia, or excessive drowsiness; if concomitant use is necessary and adverse reactions occur, reduce tizanidine dosage or discontinue. ( 7.2 , 12.3 )
7.1Strong CYP1A2 Inhibitors Concomitant use of tizanidine with strong cytochrome P450 1A2 (CYP1A2) inhibitors (e.g., fluvoxamine, ciprofloxacin) is contraindicated. Changes in pharmacokinetics of tizanidine when administered with a strong CYP1A2 inhibitor resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [see Contraindications ( 4 ) and Clinical Pharmacology ( 12.3 )].
7.2Moderate or Weak CYP1A2 Inhibitors Concomitant use of tizanidine with moderate or weak CYP1A2 inhibitors (e.g., zileuton, antiarrhythmics [amiodarone, mexiletine, propafenone, and verapamil], cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided. If concomitant use is clinically necessary, and adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce tizanidine dosage or discontinue tizanidine therapy [see Clinical Pharmacology ( 12.3 )].
7.3Oral Contraceptives Concomitant use of tizanidine with oral contraceptives is not recommended. However, if concomitant use is clinically necessary and adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce or discontinue tizanidine therapy [see Clinical Pharmacology ( 12.3 )].
7.4Alcohol and Other CNS Depressants Alcohol increases the exposure of tizanidine after administration of tizanidine. This was associated with an increase in adverse reactions of tizanidine. Concomitant use of tizanidine with CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may cause additive CNS depressant effects, including sedation.
Monitor patients who take tizanidine with another CNS depressant for symptoms of excess sedation [see Clinical Pharmacology ( 12.3 )]. 7.5 α 2 -Adrenergic Agonists Concomitant use of tizanidine with other α 2 -adrenergic agonists is not recommended because hypotensive effects may be cumulative [see Warnings and Precautions ( 5.1 )].
7.6Antihypertensive Medications Concomitant use of tizanidine tablets with antihypertensive medications may cause additive hypotensive effects [see Warnings and Precautions ( 5.1 )] . Monitor patients who take tizanidine tablets with antihypertensive medications for hypotension.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) • Geriatric use: Tizanidine should be used with caution in elderly patients because clearance is decreased four-fold ( 8.5 )
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of tizanidine tablets in pregnant women. In animal studies, administration of tizanidine during pregnancy resulted in developmental toxicity (embryofetal and postnatal offspring mortality and growth deficits) at doses less than those used clinically, which were not associated with maternal toxicity (see Animal Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of tizanidine (0.3 to 100 mg/kg/day) to pregnant rats during the period of organogenesis resulted in embryofetal and postnatal offspring mortality and reductions in body weight at doses of 30 mg/kg/day and above. Maternal toxicity was observed at the highest dose tested.
The no-effect dose for embryofetal developmental toxicity in rats (3 mg/kg/day) is similar to the maximum recommended human dose (MRHD) of 36 mg/day on a body surface area (mg/m 2 ) basis. 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 to 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 [seeNonclinical Toxicology (13.1) ].
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established. Juvenile Animal Toxicity Data Oral administration of tizanidine (0, 1, 3, and 10 mg/kg/day) to juvenile rats from postnatal day (PND) 7 through PND 70 resulted in delayed sexual maturation in males at all doses, reduced body weight gain, delayed sexual maturation in females, and bilateral corneal crystals at the mid and high doses. Corneal crystals were still observed at the mid and high doses after a three-week recovery period.
Neurobehavioral deficits were observed on a learning and memory task at the high dose. A no-effect dose for adverse effects on postnatal development not identified.
8.5Geriatric Use Tizanidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be grea…
🆘 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, ensure the adequacy of an airway and monitor cardiovascular and respiratory function. Dialysis is not likely to be an efficient method of removing tizanidine from the body [see Description ( 11 )] . In general, symptoms resolve within one to three days following discontinuation of tizanidine and administration of appropriate therapy.
Because of the similar mechanism of action, symptoms and management of tizanidine overdose are similar to that following clonidine overdose. 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.
12.2Pharmacodynamics The CNS depressant effects of tizanidine and alcohol are additive [see Warnings and Precautions ( 5.3 ) and Drug Interactions (7.4)].
12.3Pharmacokinetics Tizanidine has linear pharmacokinetics over the doses studied in clinical development [1 mg (half the recommended dosage) to 20 mg]. Tizanidine capsules and tablets are bioequivalent to each other under fasting conditions, but not under fed conditions (see Absorption, Effect of Food). Absorption 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. Effect of Food There are pharmacokinetic differences between tizanidine capsules and tizanidine tablets with respect to administration with food. 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 volunteers, of whom 81 were eligible for the statistical analysis.
Pharmacokinetics under fed conditions were different than under fasting conditions and vary by dosage form. Tablets or Capsules - Fasting T max was 1 hours after dosing T ½ was approximately 2 hours. Tablets - Fed • Mean C max was increased by approximately 30% • Median T max was increased by 25 minutes, to 1 hour and 25 minutes. • Extent of absorption was increased approximately 30% Capsules - Fed • Mean C max was decreased by 20% (consequently, approximately 66% the C max for the tablet when administered with food) • Median T max was increased 2 to 3 hours • Extent of absorption was increased approximately 10% (consequently, approximately 80% of the amount absorbed from the tablet administered with food) Capsule Content Sprinkled on Applesauce Compared to administration of an intact capsule while fasting: • C max and AUC was increased 15% to 20% • T max was decreased 15 minutes Figure 1: Mean Tizanidine Concentration vs.
Time Profiles For Tizanidine Tablets and Capsules (2 × 4 mg) Under Fasted and Fed Conditions Distribution 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. Elimination Metabolism 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.
Excretion 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 Geriatric Patients 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 [see Use in Specific Populations ( 8.5 )].
Patients with Hepatic Impairment 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 Use in Specific Populations ( 8.7 )]. Patients with Renal Impairment Tizanidine clearance is reduced by more than 50% in elderly pa…
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Tizanidine Tablets, USP 4 mg are available for oral administration as white to off-white, round, scored tablets, imprinted “APO” over “TI-4” on one side and plain with a quadrisect score on the other side. They are supplied as follows: Cartons of 100 tablets (10 tablets each blister pack x 10), NDC 0904-6418-61 WARNING: This Unit Dose package is not child resistant and is Intended for Institutional Use Only. Keep this and all drugs out of the reach of children.
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container [see USP].
📋 Description ▾
11 DESCRIPTION Tizanidine Tablets, USP contains tizanidine hydrochloride as the active ingredient, which is a central alpha 2 -adrenergic agonist. Its chemical name is 5-chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiodiazole monohydrochloride. It has a molecular formula of C 9 H 8 CIN 5 S·HCl and a molecular weight of 290.17.
Its structural formula is: Tizanidine hydrochloride is almost white to slightly yellow, crystalline powder, which is odorless or with a faint characteristic odor. Tizanidine hydrochloride is slightly soluble in water and methanol; solubility in water decreases as the pH increases. Tizanidine Tablets, USP are for oral administration and contain 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, anhydrous lactose, colloidal silicon dioxide, microcrystalline cellulose and stearic acid.
Meets USP Dissolution Test 2 chemical-structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Serious Drug Interactions Advise patients they should not take tizanidine tablets 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 healthcare providers when they start or stop taking any medication because of the risks associated with interaction between tizanidine and other medicines [see Contraindications (4) and Drug Interactions ( 7 )].
Tizanidine Tablets Dosing and Administration Tell patients to take tizanidine tablets exactly as prescribed (consistently either with or without food) and not to switch between tablets and capsules [see Dosage and Administration ( 2 )]. Inform patients that they should not take more tizanidine tablets 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 tablets, because rebound hypertension and tachycardia may occur [see Warnings and Precautions ( 5.6 )].
Hypotension Warn patients that they may experience hypotension and to be careful when changing from a lying or sitting to a standing position [see Warnings and Precautions ( 5.1 )]. Sedation Tell patients that tizanidine tablets 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 [see Warnings and Precautions ( 5.3 )]. Tell patients that the sedation may be additive when tizanidine tablets 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 tablets decreases spasticity and caution should be used. Hypersensitivity Reactions Inform patients of the signs and symptoms of severe allergic reactions and instruct them to discontinue tizanidine tablets and seek immediate medical care should these signs and symptoms occur [see Warnings and Precautions ( 5.5 )] . APOTEX INC.
Tizanidine Tablets, USP 2 mg and 4 mg Manufactured by Manufactured for Apotex Inc. Apotex Corp. Toronto, Ontario Weston, Florida Canada M9L 1T9 USA 33326 Packaged and Distributed by: MAJOR® PHARMACEUTICALS Indianapolis, IN 46268 USA Refer to package label for Distributor's NDC Number Rev.
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