What are the primary uses of tizanidine. How does tizanidine work in the body. What are the FDA-approved and off-label indications for tizanidine. What does clinical research say about tizanidine’s efficacy. How does tizanidine compare to other muscle relaxants.

Understanding Tizanidine: A Comprehensive Overview

Tizanidine, commonly known by its brand name Zanaflex, is a centrally acting alpha-2 receptor agonist widely used in the management of spasticity. This medication has gained significant attention in the medical community due to its versatility and effectiveness in treating various conditions. Let’s delve into the intricacies of this drug, exploring its uses, mechanism of action, and clinical applications.

The Primary Uses of Tizanidine: FDA-Approved and Off-Label Indications

Tizanidine’s primary FDA-approved indication is for the management of spasticity. This condition can arise from several neurological disorders, including:

• Multiple sclerosis
• Spinal cord injury
• Stroke
• Amyotrophic lateral sclerosis (ALS)
• Traumatic brain injury

However, the versatility of tizanidine extends beyond its approved uses. Healthcare providers often prescribe it off-label for various conditions:

• Chronic neck and lower back pain
• Rebound headaches due to analgesic withdrawal
• Chronic migraine headaches
• Refractory insomnia in spastic quadriplegic patients
• Regional musculoskeletal pain syndromes

Is tizanidine effective for these off-label uses? Clinical studies have shown promising results, particularly in managing chronic pain conditions and headaches. However, it’s crucial to note that off-label use should always be under the guidance of a qualified healthcare professional.

Tizanidine’s Mechanism of Action: How Does It Work?

To understand tizanidine’s effectiveness, we must explore its mechanism of action. As an imidazoline derivative and centrally acting alpha-2 receptor agonist, tizanidine works in several ways:

1. Inhibition of excitatory amino acids: Tizanidine inhibits the release of glutamate and aspartate from spinal interneurons.
2. Enhancement of presynaptic inhibition: This action leads to increased presynaptic inhibition of motor neurons.
3. Reduction of facilitation: The overall effect is a reduction in the facilitation of spinal motor neurons.
4. Action on spinal polysynaptic pathways: Tizanidine has a significant impact on these pathways.

Does tizanidine have additional effects beyond muscle relaxation? Indeed, the alpha-2 receptor-mediated inhibition of interneuronal activity also contributes to tizanidine’s anti-nociceptive and anti-convulsant properties. This multi-faceted action explains its efficacy in various conditions beyond spasticity.

Clinical Studies: Evaluating Tizanidine’s Efficacy

Numerous clinical studies have been conducted to assess tizanidine’s effectiveness in various conditions. Here’s a summary of key findings:

Spasticity Management

Placebo-controlled studies have confirmed the significant efficacy of tizanidine in reducing spasticity, particularly in patients with spinal cord-induced spasticity. Interestingly, patients with severe spasticity seem to benefit the most from tizanidine therapy.

Comparison with Other Muscle Relaxants

How does tizanidine compare to other muscle relaxants? Drug comparison studies have shown no significant differences in efficacy between tizanidine and other common muscle relaxants like baclofen or diazepam. However, tizanidine has some advantages:

• Less reported weakness compared to controls
• Fewer adverse effects compared to controlled substances
• Better overall tolerability compared to baclofen and diazepam

Multiple Sclerosis and Cerebrovascular Lesions

Studies have demonstrated that tizanidine, baclofen, and diazepam all effectively decrease excessive muscle tone in patients with multiple sclerosis or cerebrovascular lesions. However, muscle strength improvement was most significant with tizanidine.

Tizanidine in Pain Management: Beyond Spasticity

While tizanidine is primarily known for its role in spasticity management, its applications in pain management are gaining recognition. How effective is tizanidine in managing pain?

Chronic Pain Conditions

Tizanidine has shown efficacy in managing chronic neck and lumbosacral neuralgia with a myofascial component. It’s also been effective in treating regional musculoskeletal pain syndromes.

Migraine and Headache Management

Tizanidine’s off-label use extends to migraine headaches and the management of rebound headaches due to analgesic withdrawal. Its alpha-2 agonist properties contribute to its effectiveness in these conditions.

Neuropathic Pain

Animal studies have indicated that tizanidine may provide benefits in managing neuropathic pain, such as trigeminal neuralgia, similar to the effects of clonidine.

Tizanidine in Special Populations: Cerebral Palsy and Opioid Withdrawal

Tizanidine’s versatility extends to its use in specific patient populations. How is tizanidine used in these cases?

Cerebral Palsy

The American Academy of Neurology guidelines recommend tizanidine for generalized spasticity in cerebral palsy. However, for segmental or localized spasticity, treatment with botulinum toxin-A is considered more effective.

Opioid Withdrawal

Recent studies suggest that tizanidine and other alpha-2 agonists can be used for medically supervised opioid withdrawal. This application highlights the drug’s potential role in addiction medicine.

Tizanidine’s Safety Profile: Considerations for Use

While tizanidine is generally well-tolerated, it’s essential to consider its safety profile. What are the key considerations when using tizanidine?

Common Side Effects

The most common side effects of tizanidine include:

• Dry mouth
• Sedation
• Dizziness
• Fatigue

Drug Interactions

Tizanidine can interact with several medications, including:

• CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin)
• Other central nervous system depressants
• Antihypertensive medications

Healthcare providers should carefully consider these interactions when prescribing tizanidine.

Future Directions: Expanding Tizanidine’s Applications

As research into tizanidine continues, new potential applications are emerging. What future directions might we see for tizanidine?

Perioperative Management

Animal studies suggest potential benefits of tizanidine in the perioperative period. This could open up new avenues for its use in surgical settings.

Addiction Medicine

The potential use of tizanidine in opioid withdrawal management highlights its possible role in addiction medicine. Further research in this area could expand its applications significantly.

Pain Management

As our understanding of tizanidine’s mechanisms grows, we may see expanded use in various pain conditions, particularly those with a neuropathic component.

In conclusion, tizanidine represents a versatile and effective medication with applications extending far beyond its primary indication for spasticity management. Its unique mechanism of action, favorable safety profile, and potential for use in various conditions make it a valuable tool in the medical arsenal. As research continues, we may see even more applications for this remarkable drug in the future.

Tizanidine – StatPearls – NCBI Bookshelf

Continuing Education Activity

Tizanidine is an FDA-approved drug for managing spasticity. It is a centrally acting alpha-2 receptor agonist. Tizanidine effectively works with spasticity caused by multiple sclerosis, an acquired brain injury, or a spinal cord injury. It has also been shown to be clinically effective in managing patients suffering from chronic neck and lumbosacral neuralgia with a myofascial component to their pain and regional musculoskeletal pain syndromes. It is also prescribed off-label for migraine headaches, insomnia, and as an anticonvulsant. Tizanidine can also be applied as part of a detoxification therapy regimen in patients exhibiting analgesic rebound headaches to assist with analgesic withdrawal. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, toxicity, and monitoring, of tizanidine so providers can direct patient therapy as part of the inter-professional team.

Objectives:

• Explain the mechanism of action of tizanidine.

• Identify the clinical indications for tizanidine use.

• Review the adverse reaction profile of tizanidine.

• Summarize inter-professional team strategies for improving care, coordination, and communication for improving patient outcomes related to tizanidine therapy.

Access free multiple choice questions on this topic.

Indications

Tizanidine is a centrally acting alpha-2 agonist. Tizanidine is widely used as an anti-spastic agent for multiple medical conditions.

FDA-approved Indication

• Tizanidine is indicated for spasticity management due to multiple sclerosis, spinal cord injury, stroke, amyotrophic lateral sclerosis, and traumatic brain injury.[1][2][3]

Off-label Use

• Chronic neck and lower back pain[4]

• Rebound headaches due to analgesic withdrawal[5]

• Chronic migraine headaches[6]

• Refractory insomnia in spastic quadriplegic patients[7]

• Regional musculoskeletal pain syndromes[4]

Clinical Studies

• Placebo-controlled studies confirm the significant efficacy of tizanidine in reducing spasticity in patients with spinal cord-induced spasticity. Literature suggests that patients with severe spasticity are more likely to benefit from the therapy. Drug comparison studies have shown no differences in the efficacy of tizanidine compared with baclofen or diazepam. The tizanidine treatment group did not report increased weakness compared to the controls. Furthermore, patients given tizanidine experienced fewer adverse effects than those using controlled substances.[8]

• Studies exhibit that tizanidine, baclofen, and diazepam effectively decreased excessive muscle tone in patients with multiple sclerosis or cerebrovascular lesions. Muscle strength improved in all three treatment groups, but the improvement was most significant with tizanidine. Shakespeare et al. also reported similar findings showing no differences in efficacy between tizanidine, baclofen, and dantrolene compared to diazepam. However, diazepam was associated with more sedation.[9] 

• Another study by Lataste et al. showed no significant differences between tizanidine and baclofen or diazepam for muscle tone, muscle spasms, clonus, muscle strength, or overall anti-spastic effect. However, tizanidine tolerance is slightly better than diazepam and baclofen.[10]

• Groves et al. report no significant differences between tizanidine, baclofen, or diazepam for spasticity by Ashworth score. However, applying global tolerability to treatment favored tizanidine compared to baclofen and diazepam.[11] 

• Animal studies have shown that tizanidine provides benefits in the perioperative period and the management of neuropathic pain, such as trigeminal neuralgia, similar to the effects of clonidine under similar circumstances.

• A recent study indicates that tizanidine and other alpha-2 agonists can be used for medically supervised opioid withdrawal.[12]

• The American Academy of Neurology guidelines reports that tizanidine should be used for generalized spasticity in cerebral palsy, for segmental/localized spasticity treatment with botulinum toxin-A is more effective.[13]

Mechanism of Action

Tizanidine is an imidazoline derivative and a centrally acting alpha-2 receptor agonist. Tizanidine inhibits the release of excitatory amino acids like glutamate and aspartate from spinal interneurons. Consequently, tizanidine enhances the presynaptic inhibition of motor neurons. Tizanidine has significant action on spinal polysynaptic pathways.[14]

The overall effect of these actions is to reduce the facilitation of spinal motor neurons. Similarly, alpha-2 receptor-mediated inhibition of inter-neuronal activity appears to underlie tizanidine’s additional anti-nociceptive and anti-convulsant activities. Spasm frequency and clonus are also reduced by tizanidine.[15]

Tizanidine also has an affinity for the alpha-1 receptors but to a lesser degree, which may explain its mild and transitory effect on the cardiovascular system compared to clonidine despite their structural and biochemical similarity.[16]

Pharmacokinetics  

Absorption: Tizanidine has a significant, first-pass hepatic metabolism with an oral bioavailability of 20% to 34%. Tizanidine attains the steady-state concentration within 24 to 48 hours after administration. There is no noticeable change in its pharmacokinetic behavior with repeated intake.[17]

Distribution: Tizanidine has extensive tissue distribution; the volume of distribution is 2.4 L/kg. The plasma protein binding of tizanidine is approximately 30%.

Metabolism: Tizanidine is metabolized extensively in the liver by cytochrome P450-1A2 to inactive metabolites.

Excretion: Tizanidine has an elimination half-life of 2.5 hours, follows linear pharmacokinetics, and is excreted 60% through urine and 20% through feces.[18]

Administration

Tizanidine is administrated orally as 2 mg, 4 mg, and 6 mg capsules or as 2 mg and 4 mg tablets. Dosage starts with 2 mg orally and may repeat every 6 to 8 hours as needed. The dosage may gradually increase by 2 to 4 mg per dose for 1 to 4 days in between until there is a noticeably significant reduction of spasticity. Maximum dosing is three doses every 24 hours, up to 36 mg daily.

If tizanidine is used for more than nine weeks or given in high doses ranging from 20 mg to 36 mg daily, taper the dose gradually. The recommendation is to taper the dose to 2 to 4 mg daily to reduce the risk of tachycardia, rebound hypertension, and increased spasticity.[19]

The patient may open the capsule and sprinkle the contents into food. Patients can take tizanidine with food or on an empty stomach. It is important to note that the extent of absorption is greater when taken with food. The tablet and capsule dosage forms are not bioequivalent when administered with food. Hence, the clinician should counsel the patient to take tizanidine with or without food but be consistent to avoid fluctuations in concentration.[20] It is also important to recognize that smoking decreases tizanidine’s plasma concentration and exposure(AUC).[21]

Use in Specific Patient Population

Patients with Hepatic Impairment: The consequence of Hepatic impairment on the pharmacokinetics of tizanidine has not been evaluated. However, tizanidine is extensively metabolized by the liver; therefore, hepatic impairment would significantly influence the pharmacokinetics of tizanidine. Therefore, tizanidine should be avoided or used with extreme caution in patients with hepatic impairment.

Patients with Renal Impairment: Tizanidine should be used cautiously in patients with renal impairment (creatinine clearance < 25 mL/min), as clearance is decreased by more than 50%. Start with a low dose, evaluate the response to therapy, and if a higher dose is needed, the dose can be increased rather than increasing the frequency of administration. The clinician should monitor the patient closely for adverse drug reactions such as dry mouth, drowsiness, asthenia, and dizziness as indicators of toxicity.

Pregnancy Considerations: The use of tizanidine in managing spinal cord injury during pregnancy has been described in case reports.[22] However, it is important to note that tizanidine is a former FDA pregnancy category-C and should be used only if indicated after careful risk-benefit evaluation.

Breastfeeding Considerations: Tizanidine is a lipid-soluble drug; hypothetically, it may be present in breast milk; its use during lactation is not advised.

Adverse Effects

Tizanidine is generally well-tolerated. However, reports exist of potential adverse effects on several organs, such as cutaneous, gastrointestinal, neurologic, cardiovascular, endocrine, and respiratory systems.

Common Adverse Drug Reactions

• Drowsiness

• Blurred vision

• Asthenia

• Constipation

• Dyskinesia

• Nervousness

• Hallucination

• Rhinitis

• Xerostomia[15]

• Dizziness[23]

Severe Adverse Drug Reactions

• Severe hepatotoxicity and liver failure[24] 

• Anaphylaxis

• Exfoliative dermatitis

• Severe hypotension[25]

• QT interval prolongation[26]

• Severe bradycardia[27]

• Stevens-Johnson syndrome[28]

• Refractory hypokalemia and potassium wasting nephropathy[29]

Withdrawal Symptoms 

• Tachycardia

• Rebound hypertension

• Increased spasticity 

• Withdrawal symptoms are more likely to occur when discontinuing the drug abruptly. [19]

Drug Interactions

• Concomitant use of tizanidine with fluvoxamine or ciprofloxacin is contraindicated due to significant hypotension and increased psychomotor impairment.[30] A recent retrospective analysis of the WHO pharmacovigilance database identified severe cardiac and nervous system adverse drug reactions. The study concluded that the concomitant use of ciprofloxacin with tizanidine should be avoided.[31]

• Because of potential drug interactions, using tizanidine with other CYP1A2 inhibitors such as oral contraceptives containing Ethinyl estradiol and gestodene, dronedarone, pimozide, saquinavir, cimetidine, famotidine, acyclovir, and ticlopidine should be avoided due to decreased clearance of tizanidine.[32]

• If tizanidine is clinically necessary, therapy should be initiated with 2 mg and increased to 2 to 4 mg daily based on patient response to therapy.

• Adverse reactions such as hypotension, bradycardia, or excessive sedation require gradual dose reduction or stopping therapy.

• Tizanidine should be used cautiously in patients on other alpha-2 adrenergic receptor agonists.

• Patients should avoid alcohol and benzodiazepines with tizanidine as it can lead to excessive sedation and myocardial toxicity in rare instances.[33]

• Vemurafenib used in BRAF mutation-positive malignancy is an inhibitor of CYP1A2 and can increase plasma concentration of tizanidine, leading to potential toxicity.[34]

Contraindications

• Hypersensitivity to tizanidine or its ingredients is a contraindication to the use of tizanidine.

• Tizanidine use requires caution in patients with hepatic impairment. Review articles on tizanidine report cases of severe hepatotoxicity, acute liver failure, and death.[24]

• According to product labeling, tizanidine use requires caution in patients with renal impairment (creatinine clearance < 25 mL/min). In such patients, decrease the dose. If high doses are necessary, increase the individual dosage rather than the dosage frequency.

Monitoring

• Creatinine and liver function tests require measurement at baseline, then one month after the maintenance dose is achieved. Periodically monitor liver function tests in patients managed with tizanidine chronically and in higher doses.[24]

• Monitor blood pressure and heart rate before increasing the dosage because of the risk of severe hypotension associated with the higher dose.[25]

• Monitor the level of spasticity by Ashworth and modified Ashworth Scales.[35] 

• In patients with multiple sclerosis, monitor spasticity using MS Spasticity Scale(MSSS-88).[36]

Toxicity

• The maximum recommended dose of tizanidine is 36 mg/day.[37]

• In the retrospective review, which included 45 patients, the mean dose ingested was 72 mg (Above the maximum recommended dose).

Clinical Features

• Lethargy

• Bradycardia

• Hypotension

• Agitation

• Confusion

• Vomiting

• Drowsiness

• Coma

Management

• There is no antidote for tizanidine toxicity.

• Tizanidine overdose management is by close monitoring of airways, administration of intravenous fluid, and vasopressors as necessary.[25]

• The pediatric case report described an overdose of tizanidine in spastic quadriplegia and toxicity presented with multiple organ dysfunction in the absence of sepsis.[37]

• A recent case report described the altered mental status and hemodynamic instability due to tizanidine overdose, and naloxone 10 mg IV administration improved Richmond Agitation-Sedation Scale(RASS).[38] The study concluded that naloxone could be used in tizanidine overdose in emergency settings; however, naloxone does not reverse the hemodynamic parameters.[39]

Enhancing Healthcare Team Outcomes

Tizanidine is a centrally acting alpha-2 agonist prescribed to manage spasticity caused by multiple sclerosis, stroke, and spinal cord injury. Tizanidine is also used off-label for managing patients suffering from chronic neck and back pain and chronic migraines.  However, this drug can cause hypotension, bradycardia, and hepatotoxicity. Hence all healthcare providers need to understand indications, mechanisms, adverse effects, and their management. 

The clinician prescribes tizanidine for appropriate indication and should assess liver function tests at baseline and one month. In addition, the neurologist should evaluate the improvement in spasticity related to neurological disorders such as multiple sclerosis, stroke, and spinal cord injury. Nurses can check compliance, monitor for adverse events, and counsel patients for adherence to therapy. The pharmacist should verify the dosing regimen, perform medication reconciliation for drug interactions, and counsel the patient on adverse drug reactions. In addition, patients need to be warned not to combine it with antihypertensive medications. In the overdose of tizanidine, triage nurses should admit the patient, and the emergency department physicians should monitor blood pressure and heart rate and obtain 12 lead EKG. Additionally, a liver function test is required to assess for hepatotoxicity. The critical care physician should manage severe overdose, which requires vasopressors and fluids during the ICU stay.

As depicted above, there are multiple healthcare providers, including clinicians (MDs, DOs, NPs, PAs), specialists, pharmacists, and nurses, involved in taking care of the patient. Tizanidine can be an effective therapeutic agent, but it requires the entire interprofessional healthcare team to collaborate and communicate for therapy to be successful. In addition, a recent study noted that interprofessional care between clinicians, neurologists, pharmacists, nurses, physical therapists, speech and language therapists, and occupational therapists is crucial for providing patient-centered care in patients with multiple sclerosis.[40] [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

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Kerson AG, DeMaria R, Mauer E, Joyce C, Gerber LM, Greenwald BM, Silver G, Traube C. Validity of the Richmond Agitation-Sedation Scale (RASS) in critically ill children. J Intensive Care. 2016;4:65. [PMC free article: PMC5080705] [PubMed: 27800163]

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Adams A, Copley C. High dose naloxone for acute tizanidine overdose in the emergency department: a case report. Clin Toxicol (Phila). 2021 Aug;59(8):764-765. [PubMed: 33403870]

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Schmid F, Rogan S, Glässel A. A Swiss Health Care Professionals’ Perspective on the Meaning of Interprofessional Collaboration in Health Care of People with MS-A Focus Group Study. Int J Environ Res Public Health. 2021 Jun 17;18(12) [PMC free article: PMC8297392] [PubMed: 34204475]

Disclosure: Shirin Ghanavatian declares no relevant financial relationships with ineligible companies.

Disclosure: Armen Derian declares no relevant financial relationships with ineligible companies.

Side Effects, Dosage, Uses, and More

Highlights for tizanidine

1. Tizanidine oral tablet is available as both a generic and brand-name drug. Brand name: Zanaflex.
2. Tizanidine also comes as an oral capsule.
3. Tizanidine oral tablet is used to manage muscle spasms. It’s often used for people with multiple sclerosis, spinal cord injury, or muscle spasticity.

• Low blood pressure warning. Tizanidine can cause very low blood pressure that leads to dizziness or fainting. To help reduce this risk, your doctor may prescribe the lowest dose of this drug that works for you. If you already take medications that lower blood pressure, your doctor may check your blood pressure more often.
• Liver damage warning. Tizanidine can cause liver damage. If you have liver disease, talk with your doctor about whether this drug is safe for you. If you take this drug, your doctor may monitor you for changes in how well your liver works.
• Hallucinations or delusions warning. Tizanidine can cause visual hallucinations (seeing things that aren’t real). It can also cause delusions (believing things that aren’t real). If have either of these side effects, stop taking this drug and call your doctor right away.
• Sedation (drowsiness) warning. Tizanidine can cause sedation. Taking tizanidine with alcohol or certain drugs (benzodiazepines, opioids, or tricyclic antidepressants) can increase sedation. Tell your doctor or pharmacist about all medications, vitamins, or herbs you’re taking.

Tizanidine is a prescription drug that comes as an oral tablet and an oral capsule.

Tizanidine oral tablet is available as a brand-name drug Zanaflex. It’s also available as a generic drug. Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in all strengths or forms as the brand-name drug.

Why it’s used

Tizanidine oral tablet is used to manage muscle spasms. Symptoms can include muscle tightness, pain, or stiffness. This drug is often used for people with multiple sclerosis, spinal cord injury, or muscle spasticity.

How it works

Tizanidine belongs to a class of drugs called alpha-2-adrenergic agonists. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

Tizanidine reduces the activity of nerves in the spinal cord that control muscles. This helps to reduce muscle spasms.

Tizanidine oral tablet may cause drowsiness. It may also cause other side effects.

More common side effects

The more common side effects of tizanidine can include:

• dry mouth
• tiredness
• weakness
• dizziness
• urinary tract infection
• constipation
• vomiting
• trouble speaking
• runny nose
• sore throat
• vision problems

If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk with your doctor or pharmacist.

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

• Hallucinations. Symptoms can include:
  • seeing things that aren’t real
• Delusions. Symptoms can include:
  • believing things that aren’t real
• Extremely low blood pressure. Symptoms can include:
  • dizziness or lightheadedness, especially when standing after sitting or lying down
• Liver damage. Symptoms can include:
  • increased bleeding or bruising
  • yellowing of your skin or the whites of your eyes
• Sedation. Symptoms can include:
  • dizziness
  • weakness
  • fatigue and sleepiness

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare professional who knows your medical history.

Tizanidine oral tablet can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk with your doctor or pharmacist.

Examples of drugs that can cause interactions with tizanidine are listed below.

Drugs that should not be used with tizanidine

Do not take these drugs with tizanidine. When used with tizanidine, these drugs can cause dangerous effects in the body. Examples of these drugs include:

• Fluvoxamine and ciprofloxacin (Cipro). Using these drugs with tizanidine may cause very low blood pressure. It may also cause increased drowsiness or decreased muscle control.
• Other alpha-2 agonist medications such as clonidine, methyldopa, or guanfacine. Using these drugs with tizanidine can cause very low blood pressure.

Drugs that increase the risk of side effects from tizanidine

Taking tizanidine with certain medications raises your risk for side effects from tizanidine. This is because the amount of tizanidine in your body is increased. Avoid using these drugs with tizanidine if possible. Examples of these drugs include:

• Zileuton. Increased side effects can include decreased blood pressure, decreased heart rate, or extreme drowsiness.
• Certain antibiotics called fluoroquinolones (other than ciprofloxacin), such as levofloxacin, moxifloxacin, or gemifloxacin. Increased side effects can include decreased blood pressure, decreased heart rate, or extreme drowsiness.
• Certain heart rhythm drugs such as amiodarone, mexiletine, propafenone, or verapamil. Increased side effects can include decreased blood pressure, decreased heart rate, or extreme drowsiness.
• Antacids such as cimetidine or famotidine. Increased side effects can include decreased blood pressure, decreased heart rate, or extreme drowsiness.
• Oral contraceptives. Increased side effects can include decreased blood pressure, decreased heart rate, or extreme drowsiness.
• Acyclovir. Increased side effects can include decreased blood pressure, decreased heart rate, or extreme drowsiness.
• Ticlopidine. Increased side effects can include decreased blood pressure, decreased heart rate, or extreme drowsiness.

Using tizanidine with the following drugs can cause excessive sedation (drowsiness):

• benzodiazepines such as alprazolam, lorazepam, or diazepam.
• opioids such as morphine, methadone, or oxycodone.
• certain antidepressants such as amitriptyline, nortriptyline, or protriptyline.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare professional about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

Tizanidine oral tablet comes with several warnings.

Allergy warning

Tizanidine can cause a severe allergic reaction. Symptoms can include:

• trouble breathing
• itching
• swelling of your throat or tongue

If you have an allergic reaction, call your doctor or local poison control center right away. If your symptoms are severe, call 911 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Alcohol interaction warning

The use of drinks that contain alcohol increases the amount of tizanidine in your body. This can cause increased side effects from tizanidine.

Warnings for people with certain health conditions

For people with decreased liver function. Talk with your doctor about whether tizanidine is safe for you. If you take this drug, your doctor may give you a lower dose. Also, your doctor should check your liver function at the start of treatment. They may check it again 1 month after your maximum dose has been prescribed.

For people with decreased kidney function. Talk with your doctor about whether tizanidine is safe for you. If you take this drug, your doctor may give you a lower dose. Also, your doctor will watch for buildup of too much tizanidine in your body. Symptoms can include dry mouth, dizziness, or drowsiness.

Warnings for other groups

For pregnant women. Tizanidine is a category C pregnancy drug. That means two things:

1. Research in animals has shown adverse effects to the fetus when the mother takes the drug.
2. There haven’t been enough studies done in humans to be certain how the drug might affect the fetus.

Talk with your doctor if you’re pregnant or planning to become pregnant. This drug should only be used if the potential benefit justifies the potential risk to the fetus. Call your doctor if you become pregnant while taking this drug.

For women who are breastfeeding. It’s not known if tizanidine passes into breast milk and causes side effects in a child who is breastfed. Talk with your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors. The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk for side effects.

For children. This medication has not been studied in children. It should not be used in people younger than 18 years.

This dosage information is for tizanidine oral tablet. All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:

• your age
• the condition being treated
• how severe your condition is
• other medical conditions you have
• how you react to the first dose

Forms and strengths

Generic: Tizanidine

• Form: oral tablet
• Strengths: 2 mg, 4 mg

Brand: Zanaflex

• Form: oral tablet
• Strengths: 4 mg

Dosage for muscle spasms

Adult dosage (ages 18 years and older)

• Typical starting dosage: 2 mg every 6–8 hours as needed.
• Dosage increases: Your doctor may increase your dosage by 2–4 mg until your symptoms are controlled. They will wait 1–4 days between any increases.
• Maximum dosage: 3 doses in 24 hours.

Child dosage (ages 0–17 years)

This medication has not been studied in children. It should not be used in people younger than 18 years.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk for side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.

Tizanidine oral tablet is used for long-term or short-term treatment. It comes with serious risks if you don’t take it as prescribed.

If you stop taking the drug suddenly or don’t take it at all: If you stop taking tizanidine suddenly, you are at risk for withdrawal symptoms. This risk is higher if you’ve been taking high doses of the drug or taking it for a long period of time.

Withdrawal symptoms can include high blood pressure, a fast heart rate, or worsened muscle spasms. If you decide to stop this drug, your doctor should slowly decrease your dosage by 2–4 mg per day.

If you don’t take this drug at all, your muscle spasms may not improve.

If you miss doses or don’t take the drug on schedule: Your medication may not work as well or may stop working completely. If you miss too many doses, you may have withdrawal symptoms.

If you take too much: You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include:

• extreme tiredness
• confusion
• coma
• decreased heart rate
• severe decrease in blood pressure
• slowed breathing

If you think you’ve taken too much of this drug, call your doctor or seek guidance from the American Association of Poison Control Centers at 800-222-1222 or through their online tool. But if your symptoms are severe, call 911 or go to the nearest emergency room right away.

What to do if you miss a dose: Take your dose as soon as you remember. But if you remember just a few hours before your next scheduled dose, take only one dose. Never try to catch up by taking two doses at once. This could result in dangerous side effects.

How to tell if the drug is working: You should have fewer symptoms of muscle spasms. These symptoms can include muscle tightness, pain, or stiffness.

Keep these considerations in mind if your doctor prescribes tizanidine oral tablet for you.

General

• You can take tizanidine with or without food. But you should be consistent. Take it the same way each time.
• You can cut or crush the tablet.

Storage

• Store tizanidine tablets at 77°F (25°C). You can store them for a short time at temperatures between 59°F and 86°F (15°C and 30°C).
• Don’t store this medication in moist or damp areas, such as bathrooms.

Refills

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

• Always carry your medication with you. When flying, never put it into a checked bag. Keep it in your carry-on bag.
• Don’t worry about airport X-ray machines. They can’t hurt your medication.
• You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled container with you.
• Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Clinical monitoring

You and your doctor should monitor certain health issues. This can help make sure you stay safe while you take tizanidine. These issues include:

• Kidney function. Blood tests can check how well your kidneys are working. If your kidneys aren’t working well, your doctor may lower your dosage of this drug.
• Liver function. Blood tests can check how well your liver is working. If your liver isn’t working well, your doctor may lower your dosage of this drug.
• Blood pressure. Your doctor may check your blood pressure to make sure that it does not get too low while you’re taking this drug.

Availability

Not every pharmacy stocks this drug. When filling your prescription, be sure to call ahead to make sure your pharmacy carries it.

Insurance

Many insurance companies require a prior authorization for this drug. This means your doctor may need to get approval from your insurance company before your insurance company will pay for the prescription.

There are other drugs available to treat your condition. Some may be better suited for you than others. Talk with your doctor about other drug options that may work for you.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

Tizanidine – description of the substance, pharmacology, use, contraindications, formula

Contents

• Structural formula

• Russian name

• English name

• Latin name

• chemical name

• Gross formula

• Pharmacological group of the substance Tizanidine

• Nosological classification

• CAS code

• pharmachologic effect

• Characteristic

• Pharmacology

• The use of the substance Tizanidin

• Contraindications

• Use during pregnancy and lactation

• Side effects of tizanidine

• Interaction

• Overdose

• Dosage and administration

• Precautionary measures

• Information sources

• Trade names with the active substance Tizanidine

Structural formula

Russian name

Tizanidin

English name

Tizanidine

Latin name

Tizanidinum ( born Tizanidini)

Chemical name

5-Chloro-N-(4,5-dihydro-1H-imidazole- 2-yl)-2,1,3-benzothiadiazol-4-amine (as hydrochloride)

Gross formula

C ₉ H ₈ ClN ₅ S

Pharmacological substance group Tizanidin

Alpha-agonists

Drugs affecting neuromuscular transmission

Nosological classification

ICD-10 code list

CAS code

51322-75-9

Pharmacological action

Pharmacological action –

muscle relaxant , central .

Characteristics

White or almost white crystalline powder, odorless or with a slight characteristic odor. Slightly soluble in water and methanol, solubility in water decreases with increasing pH.

Pharmacology

Excites alpha ₂ -adrenergic receptors, mainly at the level of the spinal cord; reduces the release of excitatory amino acids from the intermediate neurons of the spinal cord, selectively suppresses the polysynaptic mechanisms responsible for muscle hypertonicity. Relaxes skeletal muscles in chronic spastic conditions of spinal and cerebral origin, eliminates acute painful muscle spasms and clonic convulsions. Reduces muscle resistance during passive movements, increases the strength of voluntary muscle contractions.

After oral administration, it is rapidly and almost completely absorbed. Absolute bioavailability is approximately 40%. max “> C _max is achieved in 1-2 hours. Plasma protein binding is about 30%. Biotransformed in the liver with the participation of the CYP1A2 isoenzyme to inactive or inactive metabolites. Excreted by 70% in the urine. T _1/2 – 3-5 hours

Application of the substance Tizanidine

Painful muscle spasms in diseases of the spine (including osteochondrosis, spondylosis, syringomyelia, hemiplegia, cervical and lumbar syndromes), after surgery for a herniated disc or osteoarthritis of the hip, spasticity and pain caused by neurological diseases: multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, cerebrovascular accidents, stroke, traumatic brain injury, cerebral palsy, convulsions of central origin.

Contraindications

Hypersensitivity, severe liver and kidney failure, pregnancy, lactation, childhood.

Pregnancy and Lactation Use

FDA Fetal Category C.

Breastfeeding should be discontinued during treatment (it is unknown if tizanidine is excreted in breast milk).

Side effects of the substance Tizanidine

From the side of the nervous system and sensory organs: drowsiness, fatigue, dizziness or vertigo, muscle weakness, anxiety, sleep disturbances, hallucinations.

From the CCC and blood (hematopoiesis, hemostasis): slight decrease in blood pressure (at low doses) or arterial hypertension, bradycardia.

From the gastrointestinal tract: dry mouth, nausea, gastrointestinal disorders, temporary increase in serum transaminase activity.

Interactions

Antihypertensive drugs, including diuretics, increase hypotension and bradycardia. Alcohol and sedatives deepen the depressive effect.

Overdose

Symptoms: nausea, vomiting, lowering blood pressure, dizziness, miosis, respiratory failure, coma.

Treatment: gastric lavage, activated charcoal, forced diuresis, maintenance of vital functions.

Dosage and administration

Inside. Dosing regimen should be selected individually. Tizanidine has a narrow therapeutic index and high variability in plasma levels of tizanidine in patients, so careful dose selection is required. Initial dose – 2-4 mg 3 times a day, in severe cases – an additional 2-4 mg at night. In case of neurologically caused spastic conditions, the initial dose should not exceed 6 mg per day in 3 doses with a gradual increase by 2-4 mg at intervals of 3-4 days – up to a week. The optimal therapeutic effect is usually achieved at a dose of 12-24 mg / day in 3-4 doses at regular intervals. Do not exceed a dose of 36 mg / day.

Precautions

Periodic monitoring of liver and kidney function is necessary and dose reduction if they worsen. A continuous increase in the activity of transaminases in the blood requires discontinuation. Due to possible drowsiness and weakness, it is recommended to limit the appointment to persons whose work requires a quick physical and mental reaction (operators, drivers of vehicles, etc. ).

Generalized materials www.grls.rosminzdrav.ru, 2014–2016.

Trade names with the active ingredient Tizanidine

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Lek. form
All lek. modified release capsule forms substance-powder tablets

Dosage
All dosages 2 mg 250-1000 g 4 mg 6 mg No dosage

Manufacturer
All manufacturers Avexima Sibir LLC Berezovsky Pharmaceutical Plant CJSC (CJSC “BFZ”) Veropharm JSC Veropharm JSC J.P.En. Pharma Pvt. Irbit Chemical and Pharmaceutical Plant Novartis Neva OJSC Novartis Saglik LLC Gida ve Tarim Yuryunleri Sanayi ve Ticaret A.S. Novartis Pharmaceutical Ozone LLC Sun Pharmaceutical Industries Ltd. North Star NAO Simpeks Pharma Teva Pharmaceutical Plant JSC Teva Pharmaceutical Plant Private Co. Ltd Farmak

Information for healthcare professionals only.
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instructions for use, price, analogues, composition, indications

Tablets of a round form with a flat surface with bevelled edges and risky, white or almost white color.

1 tablet contains tizanidine (as tizanidine hydrochloride) 2 mg or 4 mg;

excipients: microcrystalline cellulose, anhydrous lactose, anhydrous colloidal silicon dioxide, stearic acid.

Muscle relaxants of central action.

Pharmacodynamics. Tizanidine is a centrally acting skeletal muscle relaxant. Its main site of action is the spinal cord. By stimulating presynaptic α ₂ – adrenoreceptors, it inhibits the release of amino acids that stimulate N-methyl-D-aspartate receptors (NMDA receptors). As a result, polysynaptic signal transmission at the level of interneuronal connections in the spinal cord, which is responsible for excessive muscle tone, is inhibited, and muscle tone decreases. Tizalud is effective both in acute painful muscle spasms and in chronic spasticity of spinal and cerebral origin. It reduces resistance to passive movement, inhibits spasm and clonic convulsions, and improves the strength of active muscle contractions.

Pharmacokinetics.

Suction and distribution. Tizanidine is rapidly absorbed. Peak plasma concentrations are reached approximately 1 hour after administration. The average absolute bioavailability is 34%. The mean steady state volume of distribution (Vss) after intravenous administration is 2.6 L/kg. Plasma protein binding is 30%. Relatively low deviation of pharmacokinetic parameters among patients (C _max and AUC) facilitates a reliable preliminary assessment of plasma levels after oral administration.

Metabolism/excretion. The drug undergoes rapid and extensive metabolism in the liver. Tizanidine is metabolized primarily by CYP1A2. Metabolites are inactive. They are excreted mainly by the kidneys (70%). Elimination of total radioactivity (i.e. unchanged substance and metabolites) is biphasic, with a rapid initial phase (half-life T _1/2 = 2.5 hours) and a slower elimination phase (T _1/2 = 22 hours). Only a small amount of the substance in unchanged form (about 2.7%) is excreted by the kidneys. The average half-life of the substance in unchanged form is 2-4 hours.

Pharmacokinetics in selected groups of patients . In patients with renal insufficiency (creatinine clearance less than 25 ml / min), the average value of the maximum plasma concentration is 2 times higher than that in healthy volunteers, and the final half-life is extended to approximately 14 hours, as a result of which the area under the curve “concentration – time ”(AUC) increases on average 6 times. Studies in patients with impaired liver function have not been performed.

Tizanidine is metabolized by the CYP1A2 isoenzyme in the liver. In patients with impaired liver function, higher plasma concentrations of the substance may occur. Tizalud is contraindicated in patients with severe hepatic impairment. Pharmacokinetic data in elderly patients are limited.

Gender does not affect the pharmacokinetic properties of tizanidine.

The effect of ethnicity and race on the pharmacokinetics of tizanidine has not been studied.

The influence of food . The simultaneous use of food does not affect the pharmacokinetic profile of Tizalud tablets. Although the value of the maximum concentration increases by a third, this is not clinically significant. There was no significant effect on absorption.

• Painful muscle spasm.

• Spasticity due to multiple sclerosis.

• Spasticity due to lesions of the spinal cord.

• Spasticity due to brain damage.

• Hypersensitivity to tizanidine or any of the excipients of the drug.

• Severe liver dysfunction.

• Concomitant use of tizanidine with strong CYP1A2 inhibitors such as fluvoxamine or ciprofloxacin.

Co-administration of known CYP1A2 inhibitors may increase plasma levels of tizanidine. An increase in plasma levels of tizanidine may lead to overdose symptoms such as QT interval prolongation.

Co-administration of known CYP1A2 inducers may reduce plasma levels of tizanidine. A decrease in the level of tizanidine in the blood plasma can lead to a decrease in the therapeutic effect of Tizalud.

Co-administration of strong CYP1A2 inhibitors such as fluvoxamine or ciprofloxacin with tizanidine is contraindicated. The simultaneous use of tizanidine with fluvoxamine increases the AUC of tizanidine by 33 times, while the simultaneous use of tizanidine with ciprofloxacin increases the AUC of tizanidine by 10 times. This can lead to a clinically significant and prolonged decrease in blood pressure, accompanied by drowsiness, dizziness and reduced psychomotor productivity.

Co-administration of tizanidine with other CYP1A2 inhibitors such as antiarrhythmic drugs (amiodarone, mexiletine, propafenone), cimetidine, certain fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives and ticlopyridine is not recommended.

The simultaneous use of the drug Tizalud with antihypertensive drugs, including diuretics, can sometimes cause arterial hypotension and bradycardia. In some patients receiving concomitant treatment with antihypertensive drugs, rebound hypertension and rebound tachycardia have been observed with the sudden withdrawal of tizanidine. In some cases, rebound hypertension can cause a stroke.

Simultaneous use of the drug Tizalud with rifampicin can lead to a 50% decrease in the concentration of tizanidine. Thus, the therapeutic effect may be reduced by the use of rifampicin during therapy with Tyzalud, which may be clinically significant for some patients. Long-term simultaneous use should be avoided, and if necessary, the dosage should be adjusted very carefully.

The use of the drug Tizalud leads to a 30% decrease in the systemic effect of tizanidine in male smokers (more than 10 cigarettes per day). Long-term use of the drug in men who smoke heavily requires the appointment of higher doses of the drug.

The simultaneous use of the drug Tizalud and other drugs of central action (for example, sedatives and hypnotics (benzodiazepine or baclofen), some antihistamines and analgesics, psychotropic drugs, narcotic drugs) may enhance the effects of each of the drugs and increase the hypnotic effect of Tizalud. This applies, in particular, to the simultaneous use of alcohol, which can unpredictably change or enhance the effect of Tizalud and increase the risk of adverse reactions, so you should refrain from drinking alcohol.

The administration of the drug Tizalud together with α ₂ -adrenergic agonists (eg clonidine) should be avoided due to their potential additive hypotensive effect.

If ​​you are taking any other medicines, talk to your doctor about taking this medicine.

Co-administration of CYP1A2 inhibitors with tizanidine is not recommended.

Patients may experience hypertension and tachycardia after abrupt discontinuation of the drug or rapid dose reduction. In some cases, such rebound hypertension can cause a stroke. Treatment with tizanidine should not be stopped suddenly, but only by gradually reducing the dose.

For patients with renal insufficiency (creatinine clearance <25 ml / min), the recommended initial dose is 2 mg 1 time per day. The dose should be increased consistently, in small “steps”, taking into account the effectiveness and tolerability. To achieve a more pronounced effect, it is recommended to first increase the dose, which is prescribed 1 time per day, and then increase the frequency of administration.

Hepatic impairment associated with the use of tizanidine has been reported, but in patients receiving daily doses up to 12 mg, this was rarely observed. In this regard, it is recommended to monitor liver function once a month during the first 4 months of therapy in those patients who use tizanidine at a dose of 12 mg or more and in patients with clinical symptoms suggestive of liver failure (for example, nausea, loss of appetite, or increased fatigue of unknown etiology). The use of the drug Tizalud should be discontinued if the levels of ALT or ACT in the blood serum exceed the upper limit of normal by 3 times or more for a long period.

Arterial hypotension may occur during the use of tizanidine, as well as as a result of drug interactions with CYP1A2 inhibitors and / or antihypertensive drugs. Severe forms of arterial hypotension, such as loss of consciousness and circulatory collapse, have been reported.

Caution should be exercised when using this drug with agents that prolong the QT interval (eg cisapride, amitriptyline, azithromycin).

Caution is needed in patients with ischemic heart disease and/or heart failure. ECG monitoring should be carried out at regular intervals at the beginning of the use of the drug Tizalud in such patients.

Patients with myasthenia gravis need to carefully evaluate the risk-benefit ratio before using this medicinal product.

Experience with children and adolescents is limited, so the use of the drug Tizalud is not recommended for this category of patients.

Caution should be exercised when using this drug in elderly patients.

Tizalud tablets contain lactose. Patients with rare hereditary diseases – galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption syndrome – Tizalud tablets are not recommended.

Children.

Experience with the use of the drug in pediatrics is limited. It is not recommended to prescribe Tizalud to children.

Pregnancy.

Data on the use of the drug Tizalud in pregnant women are limited, so it should not be prescribed during pregnancy, unless the potential benefit to the mother outweighs the possible risk to the fetus.

Breastfeeding.

It has been established that tizanidine passes into breast milk in small amounts. Therefore, women who are breastfeeding should not take the drug.

Fertility.

Available data indicate that tizanidine, which was administered at a dose of 10 mg/kg/day in 90,063 male rats and at a dose of 3 mg/kg/day in female rats, did not impair fertility. Reduced fertility was observed in male rats that received tizanidine at a dose of 30 mg/kg per day and in female rats that received tizanidine at a dose of 10 mg/kg per day. Sedation, weight loss and ataxia have also been observed at these doses.

Tizanidine may cause drowsiness, dizziness and/or hypotension, thus impairing the patient’s ability to drive or use machines. The risks increase with the simultaneous use of alcohol.

Therefore, one should refrain from activities that require a high concentration of attention and quick reaction, such as driving vehicles or working with machines and mechanisms.

Tizalud has a narrow therapeutic window and high variability in plasma levels of tizanidine in different patients. Therefore, it is important to use optimal doses according to the needs of the patient. Treatment should be started with a low dose of 2 mg, which makes the risk of adverse effects from taking the drug minimal. If necessary, gradually increase the dose of the drug, observing all necessary precautions.

Adults

Relief of painful muscle spasms

Apply 2-4 mg 3 times a day. In severe cases, an additional dose of 2 or 4 mg may be taken at bedtime.

Spasticity in neurological disorders

The dose must be selected individually for each patient.

The initial daily dose should not exceed 6 mg divided into 3 doses. It can be increased to 2-4 mg 2 times gradually at intervals of 3-7 days. As a rule, the optimal therapeutic effect is achieved with a daily dose of 12-24 mg, divided into 3 or 4 doses. Do not exceed a total daily dose of 36 mg.

Special patient groups

Use in children and adolescents

The experience of using the drug Tizalud in children and adolescents is limited, therefore the drug is not recommended for use in children and adolescents.

Use in elderly patients

The experience of using the drug in elderly patients is limited, therefore, caution should be exercised when using the drug Tizalud in this category of patients. It is recommended to start treatment with the lowest dose and gradually, with caution, increase it in “small steps” until an optimal ratio of individual tolerability and therapeutic efficacy of the drug is reached.

Use in patients with impaired renal function

For patients with impaired renal function (CC <25 ml / min), the recommended initial single dose is 2 mg per day. Increasing the dose occurs gradually and with caution in "small steps", until the optimal ratio of individual tolerability and therapeutic efficacy of the drug is reached. In order to increase therapeutic efficacy, a single dose should first be increased before moving on to a more frequent daily intake of the drug.

Use in patients with impaired liver function

Treatment of patients with severe hepatic impairment is contraindicated. Tizalud is largely metabolized in the liver. The drug should be used with caution in the treatment of patients with moderately severe hepatic impairment. Treatment should begin with the lowest dosage; if necessary, increasing the dose should be carried out with caution and taking into account the individual patient tolerance of the drug Tizalud.

Treatment interruption

If necessary, interruption of drug treatment, the dose should be reduced slowly and gradually. This is especially true for patients who received an increased dose of the drug for a long time. Thus, the risk of developing a rebound increase in blood pressure and tachycardia is reduced.

There have been very few reports of drug overdose with Tyzalud.

Symptoms: nausea, vomiting, arterial hypotension, bradycardia, prolongation of the QT interval, dizziness, miosis, respiratory distress, coma, restlessness, drowsiness.

Treatment: to remove the drug from the body, repeated use of high doses of activated charcoal is recommended. Forced diuresis may accelerate the elimination of the drug. In the future, symptomatic treatment should be carried out.

Adverse reactions (such as drowsiness, fatigue, dizziness, dry mouth, low blood pressure, nausea, gastrointestinal disturbances, and elevated serum transaminase levels) are usually mild and transient in patients using low doses recommended for the relief of painful muscle spasm.

When taking doses higher than those recommended for the treatment of spasticity, the above adverse reactions occur more often and are more pronounced, but they are rarely so serious as to stop treatment. The following adverse reactions may also occur: arterial hypotension, bradycardia, muscle weakness, sleep disturbances, hallucinations and hepatitis.

The occurrence of such symptoms has been reported after abrupt withdrawal of tizanidine, in particular after long-term treatment and/or high daily doses and/or concomitant therapy with antihypertensive drugs. Under such circumstances, patients may experience hypertension and tachycardia. In some cases, such rebound hypertension can cause a stroke. Therefore, treatment with tizanidine should not be stopped suddenly, but only by gradually reducing the dose.

From the side of the psyche: insomnia, sleep disturbance; hallucinations.

From the side of the central nervous system:
drowsiness, dizziness; confusion, vertigo.

From the side of the cardiovascular system:
arterial hypotension; bradycardia; syncope.

From the gastrointestinal tract:
dry mouth, pain in the gastrointestinal tract, gastrointestinal disorders; nausea.

From the side of the hepatobiliary system:
elevated levels of serum transaminases; acute hepatitis, liver failure.

From the musculoskeletal system:
muscle weakness.

General disorders: fatigue; asthenia, withdrawal syndrome, hypersensitivity reactions.

On the part of the organs of vision: blurred vision.

Studies: decrease in blood pressure, increase in transaminase levels.