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Tizanidine 4 mg Tablet, 1,000-count — NDC 57664-503-18 (Billing 57664-0503-18)

by Sun Pharmaceutical Industries, Inc. · 1000 TABLET in 1 BOTTLE

This is a package of 1,000 tablets of Tizanidine 4 mg Tablet from Sun Pharmaceutical Industries, Inc., marketed since Dec 2003 and currently FDA-listed; retail pharmacies pay about $0.0331 per tablet (NADAC). It is the main listing for this product, which comes in 2 package sizes.

NDC 57664-0503-18
🏷️ FDA NDC (as labeled) 57664-503-18 billing pads the product segment with a zero
This package
Contains1,000-count Cost per ea$0.0331 NADAC Per package$33.10 / 1000 tablets Pack sizes2 compare ↓
Also priced by: Medicaid pays $0.1661/unit · Part D plans $0.1130/unit — full pricing hub ↓
Main listing for product 57664-503 · Also comes in: 150 tablets 57664-503-89
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

⚠️
Other active recalls for Tizanidine (different manufacturers) — 2 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Jun 26, 2023 — Failed Stability Specifications (Preferred Pharmaceuticals, Inc.) · FDA recall D-0894-2023
Class II · Jun 21, 2023 — Failed dissolution specification: Out of specification results observed in 24-month long term stability testing. (Dr Reddy's Laboratories Limited) · FDA recall D-0923-2023
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 57664-503-18
Product NDC 57664-503
11-digit billing NDC 57664050318
NCPDP billing unit EA — each (per item)
RxCUI 313412, 313413
UNII B53E3NMY5C
Application # ANDA076416
SPL Set ID 4659df31-8b89-4eff-9d86-7b7e38de416b
Established class (EPC) Central alpha-2 Adrenergic Agonist
Mechanism of action Adrenergic alpha2-Agonists
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2003-12-11
Route ORAL
Dosage form TABLET
Substance TIZANIDINE HYDROCHLORIDE
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 75100090100320
GPI class tiZANidine HCl
GCN Seq No 030274
GCN 14693
HICL code 011582
Ingredient (HICL) Tizanidine Hcl
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H6
Therapeutic class — intermediate (HIC2) Drugs Acting Principally On The Midbrain
HIC3 code H6H
Therapeutic class — specific (HIC3) Skeletal Muscle Relaxants
AHFS code 12:20.04.00
AHFS class Centrally Acting Skeletal Muscle Relaxnt
FDB label name TIZANIDINE HCL 4 MG TABLET
FDB brand name Tizanidine Hcl
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 030274
  • GCN: 14693
  • GPI-14 (Medi-Span): 75100090100320
  • HICL (First Databank): 011582
  • AHFS class code: 12:20.04.00
  • RxCUI (RxNorm): 313412
Why two NDCs? The FDA registers this code as 57664-503-18 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 57664-0503-18. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Central alpha-2 Adrenergic Agonist class.

Pharmacologic class Central alpha-2 Adrenergic Agonist
Drug family (ATC) Other centrally acting agents
How it works Adrenergic alpha2-Agonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name TIZANIDINE HCL 4 MG TABLET Ingredient Tizanidine Hcl
📗 Our plain-language guide HelloPharmacist
  • It helps manage spasticity, meaning stiff, tight muscles that are hard to control. It wears off quickly, so it is meant for the times and activities when you most need relief.
  • Food changes how much tizanidine you absorb, and tablets and capsules react differently. The key is to be consistent, either always with food or always without. Tell me or your pre...
  • Dry mouth, sleepiness, tiredness or weakness, and dizziness are the most common. Many people find them mild to moderate. Call your doctor if you faint, see things that are not ther...
  • It is best to avoid it. Alcohol raises the amount of tizanidine in your blood and adds to drowsiness and side effects. The same goes for other sedating medicines, so check with me...
📖 Read our full Tizanidine guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer eaPer package
Retail pharmacies payNADAC · weekly $0.033 $33.10 / 1000 tablets
Medicaid paysCMS SDUD · 12 mo $0.1661 $166.10 / 1000 tablets
Medicare drug plans payPart D · Q2 2026 $0.1130 $113.00 / 1000 tablets
NADAC price history (per ea) — tap or hover for the price & month
Jan 2022 Aug 2022 Jan 2026 Sep 2026 $0.056 $0.032
▼ Down 41% over the last 24 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startMarketing endStatus
57664-0503-18 You're viewing this Main listing 1000 TABLET in 1 BOTTLE $0.0331 / ea $33.06 2003-12-11 — Active
57664-0503-89 57664-503-89 150 TABLET in 1 BOTTLE $0.0331 / ea $4.96 2003-12-11 — Active

You're viewing the largest of 2 pack sizes for this product.

This pack has the lowest per-ea cost of the 2 priced pack sizes ($0.0331 NADAC).

In Medicaid, this is the most-dispensed pack of this product — about 69% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 1,000-count package — 1000 tablet in 1 bottle.
How does this package differ from NDC 57664-0503-89?
Both are Tizanidine 4 mg Tablet — the drug itself is identical. This page's package is the 1,000-count one, while NDC 57664-0503-89 is the 150 tablets package.
What NDC number is used to bill for this package of Tizanidine 4 mg Tablet?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
tizanidine 4 mg 00904-6418-61 Major 100 tablets $0.033 AB Availability likely —
Tizanidine 4 mg 16714-0172-01 NorthStar 150 tablets $0.033 AB Availability likely —
Tizanidine 4 mg 29300-0169-03 Unichem 300 tablets $0.033 AB Availability likely —
Tizanidine 4 mg 50268-0760-15 AvPAK 50 tablets $0.033 AB Availability likely —
Tizanidine 4 mgthis 57664-0503-18 Sun 1000 tablets $0.033 AB Availability likely —
Tizanidine 4 mg 68084-0645-01 American 100 tablets $0.033 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 —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2003
On the market since
Dec 2003
📍
2026
Currently FDA-listed
23 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerSun Pharmaceutical Industries, Inc.
Application holderSUN PHARMACEUTICAL INDUSTRIES INC
FDA applicationANDA076416 (ANDA)
Labeler code57664
First marketedDec 2003
Product typeHuman Prescription Drug
Portfolio890 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🍼 Nursing Mothers 🧬 Pharmacokinetics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 102 words ▾

1 INDICATIONS AND USAGE Tizanidine Tablets, USP is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with Tizanidine Tablets, USP should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration(2.1) ]. Tizanidine Tablets, USP is a central alpha-2-adrenergic agonist indicated for the management of spasticity.

Because of the short duration of therapeutic effect, treatment with Tizanidine Tablets, USP should be reserved for those daily activities and times when relief of spasticity is most important [ see Dosage and Administration (1) ].

⏱️ Dosage and Administration ~3 min read ▾

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 Tablets, USP, decrease dose slowly to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia ( 2.2 )

2.1Dosing Information Tizanidine Tablets, USP tablets may be prescribed with or without food. Once the formulation has been selected and the decision to take with or without food has been made, this regimen should not be altered. Food has complex effects on tizanidine pharmacokinetics, which differ with the different formulations.

Tizanidine Capsules and Tizanidine Tablets, USP 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 Tablets, USP 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 Tablets, USP 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 Tablets, USP should be used with caution in patients with any hepatic impairment. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased.

Monitoring of aminotransferase levels is recommended for baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected. [ see Use in Specific Populations (8.7) ]

2.4Drug Discontinuation If therapy needs to be discontinued, particularly in patients who have been receiving high doses (20 mg to 36 mg daily) for long periods (9 weeks or more) or who may be on concomitant treatment with narcotics, the dose should be decreased slowly (2 mg to 4 mg per day) to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia [ see Drug Abuse and Dependence (9.3) ].

💊 Dosage Forms and Strengths 70 words ▾

3 DOSAGE FORMS AND STRENGTHS Tizanidine Tablets, USP 2 mg are white to off-white, round, flat beveled, uncoated tablets debossed with product code “502” on one side, and bisecting score on the other. Tizanidine Tablets, USP 4 mg are white to off-white, round, flat beveled, uncoated tablets debossed with product code “503” on one side, and quadrisecting score on the other. Tablets 2 mg and 4 mg. ( 3 )

⛔ Contraindications 48 words ▾

4 CONTRAINDICATIONS Tizanidine Tablets, USP is contraindicated in patientstaking 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 ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; Tizanidine Tablets, USP should not be used with other α 2 -adrenergic agonists ( 5.1 , 7.7 ) • Risk of liver injury: monitor ALTs; discontinue Tizanidine Tablets, USP if liver injury occurs ( 5.2 ) • Sedation: Tizanidine Tablets, USP may interfere with everyday activities; sedative effects of Tizanidine Tablets, USP, alcohol, and other CNS depressants are additive ( 5.3 , 7.5 , 7.6 ) • Hallucinations: consider discontinuation of Tizanidine Tablets, USP ( 5.4 ) • Less potent inhibitors of CYP1A2: may cause hypotension, bradycardia, or excessive drowsiness, use caution if Tizanidine Tablets, USP is used with less potent inhibitors of CYP1A2, e.g., zileuton, other fluoroquinolones, antiarrythmics, cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine ( 5.5 , 7.3 , 12.3 ) • Renal impairment (creatinine clearance < 25 mL/min): use Tizanidine Tablets, USP 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 Tablets, USP is used in patients receiving concurrent antihypertensive therapy. It is not recommended thatTizanidine Tablets, USP 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 Tablets, USP. Therefore, concomitant use of Tizanidine Tablets, USP 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 Tablets, USP may cause hepatocellular liver injury. Tizanidine Tablets, USP 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 Tablets, USP 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 Tablets, USP with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive.

Monitor patients who take Tizanidine Tablets, USP with another CNS depressant for symptoms of excess sedation. [ see Drug Interactions (7.5, 7.6 ) ]

5.4Hallucinosis/Psychotic-Like Symptoms Tizanidine Tablets, USP 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 Tablets, USP in patients who develop hallucinations.

5.5Interaction with CYP1A2 Inhibitors Because of potential drug interactions, Tizanidine Tablets, USP is contraindicated… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

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 Sun Pharmaceutical Industries, Inc. toll free at 1-800-818-4555 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 Tablets, USP where the frequency in the Tizanidine Tablets, USP 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, USP Incidence is Greater than Placebo Event Placebo N = 261 % Tizanidine Tablets, USP 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… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS

7.1Fluvoxamine Concomitant use of fluvoxamine and Tizanidine Tablets, USP is contraindicated. Changes in pharmacokinetics of tizanidine when administered with fluvoxamine resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment. [ see Contraindications (4) and Clinical Pharmacology (12.3) ]

7.2Ciprofloxacin Concomitant use of ciprofoxacin and Tizanidine Tablets, USP is contraindicated. Changes in pharmacokinetics of tizanidine when administered with ciprofloxacin resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment. [ see Contraindications (4) and Clinical Pharmacology (12.3) ]

7.3CYP1A2 Inhibitors other than Fluvoxamine and Ciprofloxacin Because of potential drug interactions, concomitant use of Tizanidine Tablets, USP with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than strong CYP1A2 inhibitors (which are contraindicated), antiarrythmics (amiodarone, mexiletine, propafenone, and verapamil), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided. If their use is clinically necessary, therapy should be initiated with 2 mg dose and increased in 2–4 mg steps daily based on patient response to therapy.

If adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce or discontinue Tizanidine Tablets, USP therapy. [ see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3) ]

7.4Oral Contraceptives Concomitant use of Tizanidine Tablets, USP with oral contraceptives is not recommended. However, if concomitant use is clinically necessary, initiate Tizanidine Tablets, USP 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 Tablets, USP therapy. [ see Clinical Pharmacology (12.3) ]

7.5Alcohol Alcohol increases the overall amount of drug in the bloodstream after a dose of Tizanidine Tablets, USP. This was associated with an increase in adverse reactions of Tizanidine Tablets, USP. The CNS depressant effects of Tizanidine Tablets, USP and alcohol are additive. [ see Clinical Pharmacology (12.3) ]

7.6Other CNS Depressants The sedative effects of Tizanidine Tablets, USP with CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive. Monitor patients who take Tizanidine Tablets, USP with another CNS depressant for symptoms of excess sedation. [ see Clinical Pharmacology (12.3) ] 7.7 α 2 -adrenergic agonists Because hypotensive effects may be cumulative, it is not recommended that Tizanidine Tablets, USP be used with other α 2 -adrenergic agonists. [ see Warnings and Precautions (5.1) ]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS • Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) • Geriatric use: Tizanidine Tablets, USP should be used with caution in elderly patients because clearance is decreased four-fold ( 8.5 )

8.1Pregnancy Pregnancy Category C Tizanidine Tablets, USP has not been studied in pregnant women. Tizanidine Tablets, USP should be given to pregnant women only if the benefit outweighs the risk to the unborn fetus. Reproduction studies performed in rats at a dose of 3 mg/kg, equal to the maximum recommended human dose on a mg/m 2 basis, and in rabbits at 30 mg/kg, 16 times the maximum recommended human dose on a mg/m 2 basis, did not show evidence of teratogenicity.

Tizanidine at doses that are equal to and up to 8 times the maximum recommended human dose on a mg/m 2 basis increased gestation duration in rats. Prenatal and postnatal pup loss was increased and developmental retardation occurred. Post-implantation loss was increased in rabbits at doses of 1 mg/kg or greater, equal to or greater than 0.5 times the maximum recommended human dose on a mg/m 2 basis.

8.3Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Tizanidine Tablets, USP is administered to a nursing woman.

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.5Geriatric Use Tizanidine Tablets, USP 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 Tablets, USP 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 Tablets, USP 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 Tablets, USP.

8.6Impaired Renal Function Tizanidine Tablets, USP is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. In patients with renal insufficiency (creatinine clearance < 25 mL/min) clearance was reduced by more than 50%. In these patients, during titration, the individual doses should be reduced.

If higher doses are required, individual doses rather than dosing frequency should be increased. These patients should be monitored closely for the onset or increase in severity of the common adverse events (dry mouth, somnolence, asthenia and dizziness) as indicators of potential overdose. [ see Dosage and Administration (2.2) , Warnings and Precautions (5.7) and Clinical Pharmacology (12.3) ]

8.7Impaired Hepatic Function The influence of hepatic impairment on the pharmacokinetics of tizanidine has not been evaluated. Because tizanidine is extensively metabolized in the liver, hepatic impairment would be expected to have significant effects on pharmacokinetics of tizanidine. [ see Dosing and Administration (2.3) , Warnings and Precautions (5.2) , and Clinical Pharmacology (12.3) ].

🤰 Pregnancy 150 words ▾

8.1Pregnancy Pregnancy Category C Tizanidine Tablets, USP has not been studied in pregnant women. Tizanidine Tablets, USP should be given to pregnant women only if the benefit outweighs the risk to the unborn fetus. Reproduction studies performed in rats at a dose of 3 mg/kg, equal to the maximum recommended human dose on a mg/m 2 basis, and in rabbits at 30 mg/kg, 16 times the maximum recommended human dose on a mg/m 2 basis, did not show evidence of teratogenicity.

Tizanidine at doses that are equal to and up to 8 times the maximum recommended human dose on a mg/m 2 basis increased gestation duration in rats. Prenatal and postnatal pup loss was increased and developmental retardation occurred. Post-implantation loss was increased in rabbits at doses of 1 mg/kg or greater, equal to or greater than 0.5 times the maximum recommended human dose on a mg/m 2 basis.

🧒 Pediatric Use 13 words ▾

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

🧓 Geriatric Use 191 words ▾

8.5Geriatric Use Tizanidine Tablets, USP 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 Tablets, USP 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 Tablets, USP 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 Tablets, USP.

🆘 Overdosage 195 words ▾

10 OVERDOSAGE A review of the safety surveillance database revealed cases of intentional and accidental Tizanidine Tablets, USP 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 ~3 min read ▾

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 effect of these actions is thought to reduce facilitation of spinal motor neurons.

12.3Pharmacokinetics Absorption and Distribution Following oral administration, tizanidine is essentially completely absorbed. The absolute oral bioavailability of tizanidine is approximately 40% (CV = 24%), due to extensive first-pass hepatic metabolism. Tizanidine is extensively distributed throughout the body with a mean steady state volume of distribution of

2.4L/kg (CV = 21%) following intravenous administration in healthy adult volunteers. Tizanidine is approximately 30% bound to plasma proteins. Differences between Tizanidine Capsules and Tizanidine Tablets, USP Tizanidine Capsules and Tizanidine Tablets, USP 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 Tablets, USP and Capsules (2 × 4 mg) Under Fasted and Fed Conditions Metabolism and Excretion Tizanidine has linear pharmacokinetics over the doses studied in clinical development (1–20 mg).

Tizanidine has a half-life of approximately 2.5 hours (CV=33%). Approximately 95% of an administered dose is metabolized. The primary cytochrome P450 isoenzyme involved in tizanidine metabolism is CYP1A2.

Tizanidine metabolites are not known to be active; their half-lives range from 20 to 40 hours. Following single and multiple oral dosing of 14C-tizanidine, an average of 60% and 20% of total radioactivity was recovered in the urine and feces, respectively. Special Populations Age Effects No specific pharmacokinetic study was conducted to investigate age effects.

Cross study comparison of pharmacokinetic data following single dose administration of 6 mg Tizanidine Tablets, USP showed that younger subjects cleared the drug four times faster than the elderly subjects. Tizanidine Tablets, USP has not been evaluated in children. [ see Use in Specific Populations ( 8.4 , 8.5 ) ] Hepatic Impairment The influence of he… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 45 words ▾

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 effect of these actions is thought to reduce facilitation of spinal motor neurons.

📦 How Supplied / Storage and Handling 121 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.2Tizanidine Tablets, USP Tizanidine Tablets, USP 2 mg are available as; white to off-white, round, flat beveled, uncoated tablets debossed with product code “502” on one side, and bisecting score on the other. 2 mg Bottles of 150 NDC 57664-502-89 2 mg Bottles of 1000 NDC 57664-502-18 Tizanidine Tablets, USP 4 mg are available as; white to off-white, round, flat beveled, uncoated tablets debossed with product code “503” on one side, and quadrisecting score on the other. 4 mg Bottles of 150 NDC 57664-503-89 4 mg Bottles of 1000 NDC 57664-503-18 Store at 25°C (77°F); excursions permitted 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Dispense in containers with child resistant closure.

📋 Description 134 words ▾

11 DESCRIPTION Tizanidine Tablets, USP (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 Tablets, USP are supplied as 2 mg and 4 mg tablets for oral administration. Tizanidine Tablets, USP contain the active ingredient, tizanidine hydrochloride (2.288 mg equivalent to 2 mg tizanidine base and 4.576 mg equivalent to 4 mg tizanidine base), and the inactive ingredients, colloidal silicon dioxide, stearic acid, microcrystalline cellulose, lactose monohydrate and anhydrous lactose.

Tizanidine-1

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Serious Drug Interactions Advise patients they should not take Tizanidine Tablets, USP 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 Tablets, USP and other medicines. Tizanidine Tablets, USP Dosing Tell patients to take Tizanidine Tablets, USP 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 Tablets, USP 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, USP, because rebound hypertension and tachycardia may occur. Effects of Tizanidine Tablets, USP 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 Tablets, USP 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 Tablets, USP 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, USP decreases spasticity and caution should be used.

Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 Revised: 09/2014

🍼 Nursing Mothers 37 words ▾

8.3Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Tizanidine Tablets, USP is administered to a nursing woman.

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption and Distribution Following oral administration, tizanidine is essentially completely absorbed. The absolute oral bioavailability of tizanidine is approximately 40% (CV = 24%), due to extensive first-pass hepatic metabolism. Tizanidine is extensively distributed throughout the body with a mean steady state volume of distribution of

2.4L/kg (CV = 21%) following intravenous administration in healthy adult volunteers. Tizanidine is approximately 30% bound to plasma proteins. Differences between Tizanidine Capsules and Tizanidine Tablets, USP Tizanidine Capsules and Tizanidine Tablets, USP 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 Tablets, USP and Capsules (2 × 4 mg) Under Fasted and Fed Conditions Metabolism and Excretion Tizanidine has linear pharmacokinetics over the doses studied in clinical development (1–20 mg).

Tizanidine has a half-life of approximately 2.5 hours (CV=33%). Approximately 95% of an administered dose is metabolized. The primary cytochrome P450 isoenzyme involved in tizanidine metabolism is CYP1A2.

Tizanidine metabolites are not known to be active; their half-lives range from 20 to 40 hours. Following single and multiple oral dosing of 14C-tizanidine, an average of 60% and 20% of total radioactivity was recovered in the urine and feces, respectively. Special Populations Age Effects No specific pharmacokinetic study was conducted to investigate age effects.

Cross study comparison of pharmacokinetic data following single dose administration of 6 mg Tizanidine Tablets, USP showed that younger subjects cleared the drug four times faster than the elderly subjects. Tizanidine Tablets, USP has not been evaluated in children. [ see Use in Specific Populations ( 8.4 , 8.5 ) ] Hepatic Impairment The influence of hepatic impairment on the pharmacokinetics 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.

Tizanidine Tablets, USP is not recommended in this patient population [ see Use in Specific Populations ( 8.7 )… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES Tizanidine's capacity to reduce increased muscle tone associated with spasticity was demonstrated in two adequate and well controlled studies in patients with multiple sclerosis or spinal cord injury (Studies 1 and 2). Single-Dose Study in Patients with Multiple Sclerosis with Spasticity In Study 1, patients with multiple sclerosis were randomized to receive single oral doses of drug or placebo. Patients and assessors were blind to treatment assignment and efforts were made to reduce the likelihood that assessors would become aware indirectly of treatment assignment (e.g., they did not provide direct care to patients and were prohibited from asking questions about side effects).

In all, 140 patients received placebo, 8 mg or 16 mg of Tizanidine Tablets, USP. Response was assessed by physical examination; muscle tone was rated on a 5 point scale (Ashworth score), with a score of 0 used to describe normal muscle tone. A score of 1 indicated a slight spastic catch while a score of 2 indicated more marked muscle resistance.

A score of 3 was used to describe considerable increase in tone, making passive movement difficult. A muscle immobilized by spasticity was given a score of 4. Spasm counts were also collected.

Assessments were made at 1, 2, 3 and 6 hours after treatment. A statistically significant reduction of the Ashworth score for Tizanidine Tablets, USP compared to placebo was detected at 1, 2 and 3 hours after treatment. Figure 2 below shows a comparison of the mean change in muscle tone from baseline as measured by the Ashworth scale.

The greatest reduction in muscle tone was 1 to 2 hours after treatment. By 6 hours after treatment, muscle tone in the 8 and 16 mg Tizanidine Tablets, USP groups was indistinguishable from muscle tone in placebo treated patients. Within a given patient, improvement in muscle tone was correlated with plasma concentration.

Plasma concentrations were variable from patient to patient at a given dose. Although 16 mg produced a larger effect, adverse events including hypotension were more common and more severe than in the 8 mg group. There were no differences in the number of spasms occurring in each group.

Figure 2: Single Dose Study—Mean Change in Muscle Tone from Baseline as Measured by the Ashworth Scale ± 95% Confidence Interval (A Negative Ashworth Score Signifies an Improvement in Muscle Tone from Baseline) Seven-Week Study in Patients with Spinal Cord Injury with Spasticity In a 7-week study (Study 2), 118 patients with spasticity secondary to spinal cord injury were randomized to either placebo or Tizanidine Tablets, USP. Steps similar to those taken in the first study were employed to ensure the integrity of blinding.

Patients were titrated over 3 weeks up to a maximum tolerated dose or 36 mg daily given in three unequal doses (e.g., 10 mg given in the morning and afternoon and 16 mg given at night). Patients were then maintained on their maximally tolerated dose for 4 additional weeks (i.e., maintenance phase). Throughout the maintenance phase, muscle tone was assessed on the Ashworth scale within a period of 2.5 hours following either the morning or afternoon dose.

The number of daytime spasms was recorded daily by patients. At endpoint (the protocol-specified time of outcome assessment), there was a statistically significant reduction in muscle tone and frequency of spasms in the Tizanidine Tablets, USP treated group compared to placebo. The reduction in muscle tone was not associated with a reduction in muscle strength (a desirable outcome) but also did not lead to any consistent advantage of Tizanidine Tablets, USP treated patients on measures of activities of daily living.

Figure 3 below shows a comparison of the mean change in muscle tone from baseline as measured by the Ashworth scale. Figure 3: Seven Week Study—Mean Change in Muscle Tone 0.5–2.5 Hours After Dosing as Measured by the Ashworth Scale ± 95% Confidence Interval (A Negative Ashworth Score Signifie… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence 209 words ▾

9 DRUG ABUSE AND DEPENDENCE

9.2Abuse Abuse potential was not evaluated in human studies. Rats were able to distinguish tizanidine from saline in a standard discrimination paradigm, after training, but failed to generalize the effects of morphine, cocaine, diazepam, or phenobarbital to tizanidine.

9.3Dependence Tizanidine is closely related to clonidine, which is often abused in combination with narcotics and is known to cause symptoms of rebound upon abrupt withdrawal. Three cases of rebound symptoms on sudden withdrawal of tizanidine have been reported. The case reports suggest that these patients were also misusing narcotics.

Withdrawal symptoms included hypertension, tachycardia, hypertonia, tremor, and anxiety. Withdrawal symptoms are more likely to occur in cases where high doses are used, especially for prolonged periods, or with concomitant use of narcotics. If therapy needs to be discontinued, the dose should be decreased slowly to minimize the risk of withdrawal symptoms [ see Dosage and Administration (2.2) ].

Monkeys were shown to self-administer tizanidine in a dose-dependent manner, and abrupt cessation of tizanidine produced transient signs of withdrawal at doses > 35 times the maximum recommended human dose on a mg/m 2 basis. These transient withdrawal signs (increased locomotion, body twitching, and aversive behavior toward the observer) were not reversed by naloxone administration.

🧪 Nonclinical Toxicology 159 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Tizanidine was administered to mice for 78 weeks at oral doses up to 16 mg/kg/day, which is 2 times the maximum recommended human dose (MRHD) on a mg/m 2 basis. Tizanidine was administered to rats for 104 weeks at oral doses up to 9 mg/kg/day, which is 2.5 times the MRHD on a mg/m 2 basis. There was no increase in tumors in either species.

Mutagenesis Tizanidine was negative in in vitro (bacterial reverse mutation [Ames], mammalian gene mutation, and chromosomal aberration test in mammalian cells) and in vivo (bone marrow micronucleus, and cytogenetics) assay. Impairment of fertility Oral administration of tizanidine resulted in reduced fertility in male and female rats following doses of 30 and 10 mg/kg/day, respectively. No effect on fertility was observed at doses of 10 (male) and 3 (female) mg/kg/day, which are approximately 8 and 3 times, respectively, the MRHD on a mg/m 2 basis).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 156 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Tizanidine was administered to mice for 78 weeks at oral doses up to 16 mg/kg/day, which is 2 times the maximum recommended human dose (MRHD) on a mg/m 2 basis. Tizanidine was administered to rats for 104 weeks at oral doses up to 9 mg/kg/day, which is 2.5 times the MRHD on a mg/m 2 basis. There was no increase in tumors in either species.

Mutagenesis Tizanidine was negative in in vitro (bacterial reverse mutation [Ames], mammalian gene mutation, and chromosomal aberration test in mammalian cells) and in vivo (bone marrow micronucleus, and cytogenetics) assay. Impairment of fertility Oral administration of tizanidine resulted in reduced fertility in male and female rats following doses of 30 and 10 mg/kg/day, respectively. No effect on fertility was observed at doses of 10 (male) and 3 (female) mg/kg/day, which are approximately 8 and 3 times, respectively, the MRHD on a mg/m 2 basis).

📄 Package Label / Principal Display Panel 46 words ▾

PRINCIPAL DISPLAY PANEL - 2 mg Tablet Bottle Label NDC 57664-502-89 Tizanidine Tablets, USP Rx Only 150 Tablets ALKALOIDA Chemical Company Zrt. S:\exRanbaxy\SAN-Reg\Regulatory\spl\Deepa\2020\Tizanidine\20171111_4659df31-8b89-4eff-9d86-7b7e38de416b\Tizanidine-5.jpg

PRINCIPAL DISPLAY PANEL - 4 mg Tablet Bottle Label NDC 57664-503-89 Tizanidine Tablets, USP Rx Only 150 Tablets ALKALOIDA Chemical Company Zrt. S:\exRanbaxy\SAN-Reg\Regulatory\spl\Deepa\2020\Tizanidine\20171111_4659df31-8b89-4eff-9d86-7b7e38de416b\Tizanidine-6.jpg

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
108.7K
Units reimbursed last 4 qtrs
7.2M
Gross reimbursed last 4 qtrs
$1.2M
Avg / prescription
$11.03
Avg / unit
$0.1661
Latest quarter Q1 2026
24.7KRx
Medicaid pays / ea
$0.1661
gross reimbursed
vs
NADAC / ea
$0.0331
acquisition cost
=
Spread
+$0.1330
+402% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
41% FFS 59% MCO
Fee-for-service · 44,256 Rx Managed care · 64,437 Rx
State Medicaid map
Alaska: 10,479 units · 1,430 per 100k residents AK Maine: 40,461 units · 2,900 per 100k residents ME Washington: 123,814 units · 1,585 per 100k residents WA Idaho: 78,435 units · 3,994 per 100k residents ID Montana: 52,438 units · 4,632 per 100k residents MT North Dakota: 19,458 units · 2,485 per 100k residents ND Minnesota: 60,548 units · 1,055 per 100k residents MN Wisconsin: 161,877 units · 2,739 per 100k residents WI Michigan: 355,658 units · 3,543 per 100k residents MI New York: 501,982 units · 2,565 per 100k residents NY Vermont: 4,558 units · 704 per 100k residents VT New Hampshire: no data reported NH Oregon: 134,270 units · 3,172 per 100k residents OR Nevada: 45,037 units · 1,410 per 100k residents NV Wyoming: 14,417 units · 2,469 per 100k residents WY South Dakota: 13,239 units · 1,441 per 100k residents SD Iowa: 81,074 units · 2,528 per 100k residents IA Illinois: 121,771 units · 970 per 100k residents IL Indiana: 103,347 units · 1,506 per 100k residents IN Ohio: 452,724 units · 3,842 per 100k residents OH Pennsylvania: 258,097 units · 1,991 per 100k residents PA New Jersey: 133,091 units · 1,433 per 100k residents NJ Massachusetts: 34,900 units · 499 per 100k residents MA California: 337,913 units · 867 per 100k residents CA Utah: 99,020 units · 2,898 per 100k residents UT Colorado: 76,570 units · 1,303 per 100k residents CO Nebraska: 29,768 units · 1,505 per 100k residents NE Missouri: 453,580 units · 7,321 per 100k residents MO Kentucky: 1,059,116 units · 23,401 per 100k residents KY West Virginia: 194,103 units · 10,966 per 100k residents WV Virginia: 194,651 units · 2,233 per 100k residents VA Maryland: 97,682 units · 1,581 per 100k residents MD Connecticut: 64,299 units · 1,778 per 100k residents CT Rhode Island: 4,627 units · 423 per 100k residents RI Arizona: 64,664 units · 870 per 100k residents AZ New Mexico: 43,191 units · 2,043 per 100k residents NM Kansas: 32,465 units · 1,104 per 100k residents KS Arkansas: 62,125 units · 2,026 per 100k residents AR Tennessee: 313,612 units · 4,401 per 100k residents TN North Carolina: 300,113 units · 2,770 per 100k residents NC South Carolina: 31,297 units · 582 per 100k residents SC Delaware: 39,394 units · 3,821 per 100k residents DE Oklahoma: 218,509 units · 5,391 per 100k residents OK Louisiana: 107,522 units · 2,351 per 100k residents LA Mississippi: 103,109 units · 3,507 per 100k residents MS Alabama: 107,458 units · 2,104 per 100k residents AL Georgia: 119,042 units · 1,079 per 100k residents GA D.C.: 7,519 units · 1,107 per 100k residents DC Hawaii: no data reported HI Texas: 149,826 units · 491 per 100k residents TX Florida: 105,467 units · 466 per 100k residents FL
Units reimbursed · per 100k residents
42323,401
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Kentucky 23,401 /100k
2 West Virginia 10,966 /100k
3 Missouri 7,321 /100k
4 Oklahoma 5,391 /100k
5 Montana 4,632 /100k
6 Tennessee 4,401 /100k
7 Idaho 3,994 /100k
8 Ohio 3,842 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
1000 tablets this page57664-0503-18 108,693 Rx · $1,198,863
150 tablets57664-0503-89 47,970 Rx · $455,387
Drug total (last 4 qtrs): 156,663 Rx · 10,270,605 units · $1,654,249 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.
← 57664-0502-18 · Sun 57664-0510-83 · Sun →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.