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Zanaflex tizanidine hydrochloride 4 mg Tablet, 150-count — NDC 70515-0594-15 package photo

Zanaflex tizanidine hydrochloride 4 mg Tablet, 150-count

by Covis Pharma US, Inc · 150 TABLET in 1 BOTTLE (70515-594-15)
NDC 70515-0594-15
🏷️ FDA NDC (as labeled) 70515-594-15 billing pads the product segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced 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

🆔 Identity & classification

FDA NDC (as labeled) 70515-594-15
Product NDC 70515-594
11-digit billing NDC 70515059415
NCPDP billing unit EA — each (per item)
RxCUI 153735, 313413, 485484, 485485, 485486, 580267, 583165, 583211
UNII B53E3NMY5C
UPC 0370515602151, 0370515604155, 0370515594159, 0370515606159
Application # NDA020397
SPL Set ID 043d9e51-bfa2-4add-9058-5ece332f7e99
Established class (EPC) Central alpha-2 Adrenergic Agonist
Mechanism of action Adrenergic alpha2-Agonists
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2018-08-01
Route ORAL
Dosage form TABLET
Substance TIZANIDINE HYDROCHLORIDE
GPI-14 75100090100320
GPI class Zanaflex
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 ZANAFLEX 4 MG TABLET
FDB brand name Zanaflex
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 70515-594-15 — 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 → 70515-0594-15. 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.

🏭 Manufacturer & labeler

LabelerCovis Pharma US, Inc
Application holderLEGACY PHARMA INC SEZC
FDA applicationNDA020397 (NDA)
Labeler code70515
First marketedAug 2018
Product typeHuman Prescription Drug
Portfolio18 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.

🩺 Clinical

Label name ZANAFLEX 4 MG TABLET Ingredient Tizanidine Hcl
📖 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
  • Tizanidine is a muscle relaxant prescribed to manage spasticity — that's the uncomfortable muscle stiffness, tightness, or spasms that can come with conditions like multiple sclero...
  • Yes, it actually matters a lot — and it's different depending on whether you're taking a tablet or a capsule. Food increases how much drug your body absorbs from the tablet, but it...
  • Does it matter if I take tizanidine with food or without?
  • Very likely, yes — drowsiness is one of the most common side effects and can be significant, especially when you first start or when the dose is being adjusted. It can interfere wi...
📖 Read our full Tizanidine guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
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.

💊 What it looks like

Color blue / white
ShapeRound
ImprintA594
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 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.

4 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.

💲 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 · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
tizanidine 4 mg 00904-6418-61 Major 100 tablets $0.032 AB Availability likely —
Tizanidine 4 mg 16714-0172-01 NorthStar 150 tablets $0.032 AB Availability likely —
Tizanidine 4 mg 29300-0169-03 Unichem 300 tablets $0.032 AB Availability likely —
Tizanidine 4 mg 50268-0760-15 AvPAK 50 tablets $0.032 AB Availability likely —
Tizanidine 4 mg 57664-0503-18 Sun 1000 tablets $0.032 AB Availability likely —
Tizanidine 4 mg 68084-0645-01 American 100 tablets $0.032 AB Availability likely —
tizanidine 4 mg 00615-8469-39 NCS 30 tablets — AB FDA listed —
Tizanidine 4 mg 43063-0455-15 PD-Rx 15 tablets — AB FDA listed —
Tizanidine Hydrochloride 4 mg 49999-0347-01 Quality 120 tablets — AB FDA listed —
Tizanidine 4 mg 50090-0840-00 A-S 120 tablets — AB FDA listed —
Tizanidine 4 mg 50090-5767-00 A-S 120 tablets — AB FDA listed —
Tizanidine 4 mg 50090-6756-00 A-S 120 tablets — AB FDA listed —
Tizanidine 4 mg 50090-6757-00 A-S 90 tablets — AB FDA listed —
Tizanidine 4 mg 50090-7889-00 A-S 90 tablets — AB FDA listed —
Tizanidine 4 mg 51655-0603-20 Northwind 20 tablets — AB FDA listed —
Tizanidine 4 mg 51655-0740-26 Northwind 90 tablets — AB FDA listed —
Tizanidine 4 mg 55111-0180-03 Dr. 300 tablets — AB FDA listed —
tizanidine 4 mg 55154-7287-00 Cardinal 10 tablets — AB FDA listed —
tizanidine 4 mg 60505-0252-01 Apotex 100 tablets — AB FDA listed —
Tizanidine 4 mg 60760-0505-04 St. 4 tablets — AB FDA listed —
Tizanidine Hydrochloride 4 mg 61919-0196-30 TIZANIDINE 30 tablets — AB FDA listed —
Tizanidine 4 mg 63187-0009-30 Proficient 30 tablets — AB FDA listed —
tizanidine 4 mg 63187-0145-30 Proficient 30 tablets — AB FDA listed —
Tizanidine 4 mg 63187-0493-15 Proficient 15 tablets — AB FDA listed —
Tizanidine 4 mg 63187-0673-14 Proficient 14 tablets — AB FDA listed —
Tizanidine 4 mg 63629-1673-00 Bryant 112 tablets — AB FDA listed —
Tizanidine 4 mg 63629-2371-01 Bryant 1000 tablets — AB FDA listed —
tizanidine 4 mg 64980-0659-03 Rising 30 tablets — AB FDA listed —
tizanidine 4 mg 67046-1444-03 Coupler 30 tablets — AB FDA listed —
Tizanidine 4 mg 67296-2263-02 Redpharm 15 tablets — AB FDA listed —
Tizanidine 4 mg 67877-0614-05 Ascend 500 tablets — AB FDA listed —
tizanidine 4 mg 68071-3719-03 NuCare 30 tablets — AB FDA listed —
Tizanidine 4 mg 68071-4463-03 NuCare 30 tablets — AB FDA listed —
Tizanidine 4 mg 68071-5268-03 NuCare 30 tablets — AB FDA listed —
Tizanidine 4 mg 68788-7781-01 Preferred 100 tablets — AB FDA listed —
tizanidine 4 mg 68788-8741-01 Preferred 100 tablets — AB FDA listed —
Tizanidine 4 mg 68788-8802-01 Preferred 100 tablets — AB FDA listed —
Zanaflex 4 mgthis 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 —
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
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
Aug 2018
📍
2026
Currently FDA-listed
8 years listed
🔒
·
Generic approved (availability unconfirmed)
see note
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

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.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Zanaflex — the program that covers self-administered drugs. 2 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Zanaflex. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$950.9K
Claims incl. refills
417
Beneficiaries
266
Spend / beneficiary
$3,574.96
Spend / claim
$2,280.43
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Zanaflex (this brand).

Top reported reactions

Fatigue1,518
Pain1,453
Nausea1,450
Headache1,410
Fall1,030
Dizziness926
Diarrhoea880

Reporter sex

17,971 reports

Serious outcomes

Disabling409
Life-threatening352
Reports over time (by year) — tap or hover for the count & year
2020 2022 2024 2026 1,262 642
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
70515-0594-15 You're viewing this 150 TABLET in 1 BOTTLE (70515-594-15) 2018-08-01 Active

🧭 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 FDA registers it as 70515-594-15, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 70515-0594-15, written without dashes as 70515059415. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 70515-0594-15, the first segment (70515) is the labeler code FDA assigned to Covis Pharma US, Inc; the middle segment (0594) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (15) identifies this exact package size and type. Together they name one specific package of one specific product.
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 Covis Pharma US, Inc. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Covis Pharma US, Inc 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.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. 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
🎯 Indications and Usage 89 words ▾

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

Because of the short duration of therapeutic effect, treatment with Zanaflex should be reserved for those daily activities and times when relief of spasticity is most important. ( 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 Zanaflex, decrease dose slowly to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia ( 2.2 )

2.1Dosing Information Zanaflex Capsules ® or Zanaflex ® 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.

Zanaflex Capsules and Zanaflex tablets are bioequivalent to each other under fasting conditions (more than 3 hours after a meal), but not under fed conditions (within 30 minutes of a meal). These pharmacokinetic differences may result in clinically significant differences when switching administration of tablet and capsules and when switching administration between the fed or fasted state. These changes may result in increased adverse events, or delayed or more rapid onset of activity, depending upon the nature of the switch.

For this reason, the prescriber should be thoroughly familiar with the changes in kinetics associated with these different conditions [see Clinical Pharmacology ( 12.3 )] . The recommended starting dose is 2 mg. Because the effect of Zanaflex 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 Zanaflex 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 Zanaflex 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 100 words ▾

3 DOSAGE FORMS AND STRENGTHS Capsules 2 mg: Light blue opaque body with a light blue opaque cap with “2 MG” printed on the cap 4 mg: White opaque body with a blue opaque cap with “4 MG” printed on the cap 6 mg: Blue opaque body with a white stripe and blue opaque cap with “6 MG” printed on the cap Tablets 4 mg white, uncoated tablets with a quadrisecting score on one side and debossed with “A594” on the other side Capsules: 2 mg, 4 mg or 6 mg ( 3 ) Tablets 4 mg ( 3 )

⛔ Contraindications 47 words ▾

4 CONTRAINDICATIONS Zanaflex is contraindicated in patients taking potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin [see Drug Interactions ( 7.1 , 7.2 )] . Concomitant use with potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin ( 4 , 5.5 , 7.1 , 7.2 )

⚠️ Warnings and Cautions ~3 min read ▾

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

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

5.4Hallucinosis/Psychotic-Like Symptoms Zanaflex 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 Zanaflex in patients who develop hallucinations.

5.5Interaction with CYP1A2 Inhibitors Because of potential drug interactions, Zanaflex is contraindicated in patients taking potent CYP1A2 inhibitors, such as fluvoxamine or ciprofloxacin. Adverse reactions such as hypotension, bradycardia, or excessive drowsiness can occur when Zanaflex is taken with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than ciprofloxacin (which…

🤒 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 Covis Pharma at 1-866-488-4423 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 Zanaflex where the frequency in the Zanaflex 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 Zanaflex Tablets Incidence is Greater than Placebo Event Placebo N = 261 % Zanaflex Tablet N = 264 % Dry mouth 10 49 Somnolence 10 48 Asthenia (weakness, fatigue, and/or tiredness) 16 41 Dizziness 4 16 UTI 7 10 Infection 5 6 Constipation 1 4 Liver test abnormality 2 6 Vomiting 0 3 Speech disorder 0 3 Amblyopia (blurred vision) <1 3 Urinary frequency 2 3 Flu syndrome 2 3 Dyskinesia 0 3 Nervousness <1 3 Pharyngitis 1 3 Rhinitis 2 3 In the single dose, placebo-controlled study involving 142 patients with spasticity due to multiple sclerosis (Study 1) [see Clinical Studies ( 14 )] , the patients were specifically asked if they had experienced any of the four most common adverse reactions: dry mouth, somnolence (drowsiness), asthenia (weakness, fatigue and/or tiredness) and dizziness.

In addition, hypotension and bradycardia were observed. The occurrence of these reactions is summarized in Table 2 . Other events were, in general, reported at a rate of 2% or less.

Table 2: Single Dose, Placebo-Controlled Study - Common Adverse Reactions Reported Event Placeb…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS

7.1Fluvoxamine Concomitant use of fluvoxamine and Zanaflex 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 ciprofloxacin and Zanaflex 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 Zanaflex with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than strong CYP1A2 inhibitors (which are contraindicated), antiarrhythmics (amiodarone, mexiletine, propafenone, and verapamil), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided. If their use is clinically necessary, therapy should be initiated with 2 mg dose and increased in 2–4 mg steps daily based on patient response to therapy.

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

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

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

7.6Other CNS Depressants The sedative effects of Zanaflex with CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive. Monitor patients who take Zanaflex 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 Zanaflex 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: Zanaflex 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 Zanaflex in pregnant women. In animal studies, administration of tizanidine during pregnancy resulted in developmental toxicity (embryofetal and postnatal offspring mortality and growth deficits) at doses less than those used clinically, which were not associated with maternal toxicity (see Animal Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively.

The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of tizanidine (0.3 to 100 mg/kg/day) to pregnant rats during the period of organogenesis resulted in embryofetal and postnatal offspring mortality and reductions in body weight at doses of 30 mg/kg/day and above. Maternal toxicity was observed at the highest dose tested.

The no-effect dose for embryofetal developmental toxicity in rats (3 mg/kg/day) is similar to the maximum recommended human dose (MRHD) of 36 mg/day on a body surface area (mg/m 2 ) basis. Oral administration of tizanidine (1 to 100 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in embryofetal and postnatal offspring mortality at all doses. Maternal toxicity was observed at the highest dose tested.

Oral administration of tizanidine (10 and 30 mg/kg/day) during the perinatal period of pregnancy (2-6 days prior to delivery) resulted in increased postnatal offspring mortality at both doses. A no-effect dose for embryofetal developmental toxicity in rabbit was not identified. The lowest dose tested (1 mg/kg/day) is less than the MRHD on a mg/m 2 basis.

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

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

8.5Geriatric Use Zanaflex 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 Zanaflex 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 Zanaflex showed that younger subjects cleared the drug four times faster than the elderly subjects. In elderly patients with renal insufficiency (creatinine clear…

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of Zanaflex in pregnant women. In animal studies, administration of tizanidine during pregnancy resulted in developmental toxicity (embryofetal and postnatal offspring mortality and growth deficits) at doses less than those used clinically, which were not associated with maternal toxicity (see Animal Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively.

The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of tizanidine (0.3 to 100 mg/kg/day) to pregnant rats during the period of organogenesis resulted in embryofetal and postnatal offspring mortality and reductions in body weight at doses of 30 mg/kg/day and above. Maternal toxicity was observed at the highest dose tested.

The no-effect dose for embryofetal developmental toxicity in rats (3 mg/kg/day) is similar to the maximum recommended human dose (MRHD) of 36 mg/day on a body surface area (mg/m 2 ) basis. Oral administration of tizanidine (1 to 100 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in embryofetal and postnatal offspring mortality at all doses. Maternal toxicity was observed at the highest dose tested.

Oral administration of tizanidine (10 and 30 mg/kg/day) during the perinatal period of pregnancy (2-6 days prior to delivery) resulted in increased postnatal offspring mortality at both doses. A no-effect dose for embryofetal developmental toxicity in rabbit was not identified. The lowest dose tested (1 mg/kg/day) is less than the MRHD on a mg/m 2 basis.

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

🧒 Pediatric Use 13 words ▾

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

🧓 Geriatric Use 184 words ▾

8.5Geriatric Use Zanaflex 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 Zanaflex 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 Zanaflex 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 Zanaflex.

🆘 Overdosage 193 words ▾

10 OVERDOSAGE A review of the safety surveillance database revealed cases of intentional and accidental Zanaflex 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 overall effect of these actions is thought to reduce facilitation of spinal motor neurons.

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

2.4L/kg (CV = 21%) following intravenous administration in healthy adult volunteers. Tizanidine is approximately 30% bound to plasma proteins. Differences Between Zanaflex Capsules® and Zanaflex® Tablets Zanaflex Capsules ® and Zanaflex ® tablets are bioequivalent to each other under fasting conditions, but not under fed conditions.

A single dose of either two 4 mg tablets or two 4 mg capsules was administered under fed and fasting conditions in an open label, four period, randomized crossover study in 96 human volunteers, of whom 81 were eligible for the statistical analysis. Following oral administration of either the tablet or capsule (in the fasted state), peak plasma concentrations of tizanidine occurred 1.0 hours after dosing with a half-life of approximately 2 hours. When two 4 mg tablets were administered with food, the mean maximal plasma concentration was increased by approximately 30%, and the median time to peak plasma concentration was increased by 25 minutes, to 1 hour and 25 minutes.

In contrast, when two 4 mg capsules were administered with food, the mean maximal plasma concentration was decreased by 20%, the median time to peak plasma concentration was increased 2 to 3 hours. Consequently, the mean C max for the capsule when administered with food is approximately 66% the C max for the tablet when administered with food. Food also increased the extent of absorption for both the tablets and capsules.

The increase with the tablet (~30%) was significantly greater than with the capsule (~10%). Consequently, when each was administered with food, the amount absorbed from the capsule was about 80% of the amount absorbed from the tablet. Administration of the capsule contents sprinkled on applesauce was not bioequivalent to administration of an intact capsule under fasting conditions.

Administration of the capsule contents on applesauce resulted in a 15%–20% increase in C max and AUC of tizanidine and a 15 minute decrease in the median lag time and time to peak concentration compared to administration of an intact capsule while fasting. Metabolism and Excretion Tizanidine has linear pharmacokinetics over the doses studied in clinical development (1–20 mg). Tizanidine has a half-life of approximately 2.5 hours (CV=33%).

Approximately 95% of an administered dose is metabolized. The primary cytochrome P450 isoenzyme involved in tizanidine metabolism is CYP1A2. Tizanidine metabolites are not known to be active; their half-lives range from 20 to 40 hours.

Following single and multiple oral dosing of 14 C-tizanidine, an average of 60% and 20% of total radioactivity was recovered in the urine and feces, respectively. Specific Populations Age Effects No specific pharmacokinetic study was conducted to investigate age effects. Cross study comparison of pharmacokinetic data following single dose administration of 6 mg Zanaflex showed that younger subjects cleared the drug four times faster than the elderly subjects.

Zanaflex 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 expecte…

🧬 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 ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1Zanaflex Capsules® Zanaflex Capsules ® (tizanidine hydrochloride) capsules are available in three strengths as two-piece hard gelatin capsules containing tizanidine hydrochloride 2.29 mg, 4.58 mg and 6.87 mg, equivalent to 2 mg, 4 mg and 6 mg tizanidine base. The 2 mg capsules have a light blue opaque body with a light blue opaque cap with “2 MG” printed on the cap: bottles of 150 capsules (NDC 70515-602-15) The 4 mg capsules have a white opaque body with a blue opaque cap with “4 MG” printed on the cap: bottles of 150 capsules (NDC 70515-604-15) The 6 mg capsules have a blue opaque body with a white stripe and blue opaque cap with “6 MG” printed on the capsules: bottles of 150 capsules (NDC 70515-606-15) Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Dispense in containers with child resistant closure.

16.2Zanaflex® Tablets Zanaflex ® (tizanidine hydrochloride) tablets are available as 4 mg white, uncoated tablets containing tizanidine hydrochloride 4.58 mg, equivalent to 4 mg tizanidine base. The tablets have a quadrisecting score on one side and are debossed with “A594” on the other side. Tablets are provided as follows: bottles of 150 tablets (NDC 70515-594-15).

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense in containers with child resistant closure.

📋 Description 183 words ▾

11 DESCRIPTION Zanaflex ® (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: Zanaflex Capsules ® are supplied as 2, 4, and 6 mg capsules for oral administration. Zanaflex Capsules ® contain the active ingredient, tizanidine hydrochloride (2.29 mg equivalent to 2 mg tizanidine base, 4.58 mg equivalent to 4 mg tizanidine base, and 6.87 mg equivalent to 6 mg tizanidine base), and the inactive ingredients, hypromellose, silicon dioxide, sugar spheres, titanium dioxide, gelatin, and colorants.

Zanaflex ® tablets are supplied as 4 mg tablets for oral administration. Zanaflex ® tablets contain the active ingredient, tizanidine hydrochloride (4.58 mg equivalent to 4 mg tizanidine base), and the inactive ingredients, colloidal silicon dioxide, stearic acid, microcrystalline cellulose and anhydrous lactose. Structural Formula

💬 Information for Patients ~1 min read ▾

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

Zanaflex ® capsules is a registered trademark of Covis Pharma. Zanaflex ® tablets is a registered trademark of Covis Pharma. Manufactured for: Covis Pharma Zug, 6300 Switzerland ©2020 Covis Pharma, All rights reserved.

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