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tizanidine 4 mg Tablet, 1,000-count — NDC 70771-1336-00 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

tizanidine 4 mg Tablet, 1,000-count — NDC 70771-1336-0 (Billing 70771-1336-00)

by Zydus Lifesciences Limited · 1000 TABLET in 1 BOTTLE

This is a package of 1,000 tablets of tizanidine 4 mg Tablet from Zydus Lifesciences Limited, marketed since Sep 2018 and currently FDA-listed. It is the main listing for this product, which comes in 4 package sizes.

NDC 70771-1336-00
🏷️ FDA NDC (as labeled) 70771-1336-0 billing pads the package segment with a zero
This package
Contains1,000-count Pack sizes4 compare ↓
Also priced by: Part D plans $0.1130/unit — full pricing hub ↓
Main listing for product 70771-1336 · Also comes in: 30 tablets 70771-1336-3 100 tablets 70771-1336-4 150 tablets 70771-1336-8
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) 70771-1336-0
Product NDC 70771-1336
11-digit billing NDC 70771133600
RxCUI 313412, 313413
UNII B53E3NMY5C
Application # ANDA208187
SPL Set ID 89105a78-badb-469e-966e-195fa3a53f0a
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 2018-09-13
Route ORAL
Dosage form TABLET
Substance TIZANIDINE HYDROCHLORIDE
TE code (Orange Book) AB · RLD · RS
Quick answers
  • RxCUI (RxNorm): 313412
Why two NDCs? The FDA registers this code as 70771-1336-0 — a 5-4-1 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 package segment → 70771-1336-00. 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

📖 What it is MedlinePlus · NLM

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 ↗
📗 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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $0.1130 $113.00 / 1000 tablets
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 Marketing startMarketing endStatus
70771-1336-00 You're viewing this Main listing 1000 TABLET in 1 BOTTLE 2018-09-13 — Active
70771-1336-03 70771-1336-3 30 TABLET in 1 BOTTLE 2018-09-13 — Active
70771-1336-04 70771-1336-4 10 BLISTER PACK in 1 CARTON / 10 TABLET in 1 BLISTER PACK 2018-09-13 — Active
70771-1336-08 70771-1336-8 150 TABLET in 1 BOTTLE 2018-09-13 — Active

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 70771-1336-03?
Both are tizanidine 4 mg Tablet — the drug itself is identical. This page's package is the 1,000-count one, while NDC 70771-1336-03 is the 30 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.

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 mg 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 mgthis 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

🏛️
2018
On the market since
Sep 2018
📍
2026
Currently FDA-listed
8 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.

What it looks like

Color White
ShapeRound
Imprint1105
Size9 mm
ScoringScored — splits in 4
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • 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.
  • 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.
  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • 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.
  • 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.

5 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — 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

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

LabelerZydus Lifesciences Limited
Application holderCADILA HEALTHCARE LTD
FDA applicationANDA208187 (ANDA)
Labeler code70771
First marketedSep 2018
Product typeHuman Prescription Drug
Portfolio720 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 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 31 words ▾

1 INDICATIONS AND USAGE Tizanidine tablets are a central alpha-2-adrenergic agonist indicated for the treatment of spasticity. ( 1 ) Tizanidine tablets are indicated for the treatment of spasticity in adults.

⏱️ Dosage and Administration ~3 min read ▾

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 Tablets 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 tablets 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 tablets should be reserved for those daily activities and times when relief of spasticity is most important.

2.3Recommended Dosage in Patients with Renal Impairment In 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 In 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 73 words ▾

3 DOSAGE FORMS AND STRENGTHS Tablets: 2 mg and 4 mg ( 3 ) Tablets The 2 mg tablets are white to off-white, round, uncoated tablet debossed with '1' & '1' on either side of bisecting score on one side and debossed with '04' on the other side. The 4 mg tablets are white to off-white, round, uncoated tablet with quadrisecting score on one side and debossed with '1105' on the other side.

⛔ Contraindications 72 words ▾

4 CONTRAINDICATIONS 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 ) Tizanidine tablets are 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) ].

⚠️ 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 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 [see Adverse 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 mg to 28 mg daily) for long periods o… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS 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 Zydus Pharmaceuticals USA Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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)]

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 mg/day 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. Table1:Multiple Dose, Placebo-Controlled Studies—Adverse Reactions Reported for 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 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 * 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.

Table2:SingleDose , Placebo-ControlledStudy—CommonAdverseReactionsReported 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… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

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 a2-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 with antihypertensive medications may cause additive hypotensive effects [see Warnings and Precautions (5.1) ]. Monitor patients who take tizanidine with antihypertensive medications for hypotension.

👥 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 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 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 mg/kg/day 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 mg/kg/day 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 mg/kg/day 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 mg/kg/day to 30 mg/kg/day) resulted in increased postnatal offspring mortality. A no-effect dose for pre- and postnatal developmental toxicity was not identified. The lowest dose tested (3 mg/kg/day) is similar to the MRHD on a mg/m 2 basis, respectively.

8.2Lactation Risk Summary There are no data on the presence of tizanidine in human milk, the effects on the breastfed infant, or the effects on human milk production. Animal studies have reported the presence of tizanidine in the milk of lactating animals. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for tizanidine and any potential adverse effects on the breastfed infant from tizanidine or from the underlying maternal condition.

8.3Females and Males of Reproductive Potential There are no adequate and well-controlled studies in humans on the effect of tizanidine on female or male reproductive potential. Oral administration of tizanidine to male and female rats resulted in adverse effects on fertility [see Nonclinical 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 react… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of tizanidine in pregnant women. In animal studies, administration of tizanidine during pregnancy resulted in developmental toxicity (embryofetal and postnatal offspring mortality and growth deficits) at doses less than those used clinically, which were not associated with maternal toxicity (see Animal Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% 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 mg/kg/day 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 mg/kg/day 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 mg/kg/day 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 mg/kg/day to 30 mg/kg/day) resulted in increased postnatal offspring mortality. A no-effect dose for pre- and postnatal developmental toxicity was not identified. The lowest dose tested (3 mg/kg/day) is similar to the MRHD on a mg/m 2 basis, respectively.

🧒 Pediatric Use 108 words ▾

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.

🧓 Geriatric Use 171 words ▾

8.5Geriatric Use Tizanidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Clinical studies of tizanidine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects.

Pharmacokinetic data showed that younger subjects cleared tizanidine faster than the elderly subjects [see Clinical Pharmacology (12.3) ] . In elderly patients with renal insufficiency (creatinine clearance <25 mL/min), tizanidine clearance is reduced compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. During titration, the individual doses should be reduced.

If higher doses are required, individual doses rather than dosing frequency should be increased. Monitor elderly patients because they may have an increased risk for adverse reactions associated with tizanidine.

🆘 Overdosage 175 words ▾

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 ~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 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 Tizanidine Capsules (2 mg x 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 patients… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 46 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 overall effect of these actions is thought to reduce facilitation of spinal motor neurons.

📦 How Supplied / Storage and Handling 199 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Tizanidine Tablets USP, 2 mg are white to off-white, round, uncoated tablet debossed with '1' & '1' on either side of bisecting score on one side and debossed with '04' on the other side and are supplied as follows: NDC 72578-096-06 in bottles of 30 tablets with child-resistant closure. NDC 72578-096-21 in bottles of 150 tablets with child-resistant closure. NDC 72578-096-10 in bottles of 1000 tablets NDC 72578-096-77 in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets Tizanidine Tablets USP, 4 mg are white to off-white, round, uncoated tablet with quadrisecting score on one side and debossed with '1105' on the other side and are supplied as follows: NDC 72578-097-06 in bottles of 30 tablets with child-resistant closure.

NDC 72578-097-21 in bottles of 150 tablets with child-resistant closure. NDC 72578-097-76 in bottles of 300 tablets with child-resistant closure. NDC 72578-097-10 in bottles of 1000 tablets NDC 72578-097-77 in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets

16.2Storage and Handling Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight container as defined in the USP with a child-resistant closure.

📋 Description 164 words ▾

11 DESCRIPTION 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. Tizanidine Hydrochloride is a white to slightly yellow crystalline powder.

Tizanidine is slightly soluble in water and methanol. Each tizanidine tablet intended for oral administration contains 2.29 mg or 4.58 mg of tizanidine hydrochloride USP, which is equivalent to 2 mg or 4 mg of tizanidine base. In addition, each tablet contains the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, microcrystalline cellulose and stearic acid.

Meets USP Dissolution Test 2. figure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Serious Drug Interactions Advise patients they should not take tizanidine 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 Dosing and Administration Tell patients to take tizanidine 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 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, 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 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 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 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 and seek immediate medical care should these signs and symptoms occur [see Warnings and Precautions (5.5) ]. Manufactured by: Zydus Lifesciences Ltd., Matoda, Ahmedabad, India Rev.: 12/24

🍼 Nursing Mothers 47 words ▾

8.3Females and Males of Reproductive Potential There are no adequate and well-controlled studies in humans on the effect of tizanidine on female or male reproductive potential. Oral administration of tizanidine to male and female rats resulted in adverse effects on fertility [see Nonclinical Toxicology (13.1) ].

🧬 Pharmacokinetics ~3 min read ▾

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 Tizanidine Capsules (2 mg x 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 patients with renal insufficiency (creatinine clearance < 25 mL/min) compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect [see Use in Specific Populations (8.6) ].

Gender Effects No specific pharmacokinetic study was conducted to investigate gender effects. Retrospective analysis of pharmacokinetic data following single and multiple dose administration of 4 mg tizanidine, however, showed that gender had no effect on the pharmacokinetics of tizanidine. Drug Intera… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES The efficacy of tizanidine for the treatment of 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, 140 patients with spasticity caused by multiple sclerosis were randomized to receive single oral doses of 8 mg or 16 mg of tizanidine, or placebo. Patients and assessors were blinded 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).

Response was assessed by physical examination; muscle tone was rated on a 5-point scale (Ashworth score) as follows: 0 = normal muscle tone 1 = slight spastic catch 2 = more marked muscle resistance 3 = considerable increase in tone, making passive movement difficult 4 = a muscle immobilized by spasticity 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 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 mg and 16 mg tizanidine groups was indistinguishable from muscle tone in patients who received placebo.

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 reactions 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. 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 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 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 to

2.5Hours After Dosing as Measured by the Ashworth Scale ± 95% Confidence Interval (A Negative Ashworth Score Signifies an Improvement in Muscle Tone from Baseline) figure figure

🔒 Drug Abuse and Dependence ~1 min read ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Tizanidine tablets contains tizanidine, which is not a controlled substance.

9.2Abuse Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. 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 Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. 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. 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 (2.5 )]. 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 182 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) of 36 mg/day on a body surface area (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 to rats prior to and during mating and continuing during early pregnancy in females resulted in reduced fertility in male and female rats at doses of 30 mg/kg/day 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 3 times and similar to the MRHD, respectively, on a mg/m 2 basis.

📄 Recent Major Changes 45 words ▾

RECENT MAJOR CHANGES Indications and Usage ( 1 ) 11/2024 Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 , 2.5 , 2.6 ) 11/2024 Contraindications ( 4 ) 11/2024 Warnings and Precautions ( 5.1 , 5.2 , 5.4 , 5.5 ) 11/2024

📄 Package Label / Principal Display Panel 38 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 70771-1335-8 in bottles of 150 tablets Tizanidine Tablets USP, 2 mg 150 Tablets Rx only NDC 70771-1336-8 in bottles of 150 tablets Tizanidine Tablets USP, 4 mg 150 Tablets Rx only figure figure

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

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Zydus Lifesciences Limited. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 3 other package presentations of this same product, including 30 tablets (70771-1336-03), 100 tablets (70771-1336-04), 150 tablets (70771-1336-08). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Zydus Lifesciences Limited is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 70771-1335-00 · Zydus 70771-1338-00 · Zydus →
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.