What is tizanidine 4mg used for. How does tizanidine work to relieve muscle spasticity. What are the potential side effects of taking tizanidine. How should tizanidine be taken for maximum effectiveness. What precautions should be considered when using tizanidine.

Understanding Tizanidine: A Powerful Muscle Relaxant

Tizanidine, also known by its brand name Zanaflex, is a short-acting muscle relaxant that belongs to the drug class of skeletal muscle relaxants. This medication works by blocking nerve impulses, specifically pain sensations, that are sent to the brain. By doing so, tizanidine effectively treats spasticity by temporarily relaxing muscle tone.

But what exactly is spasticity? Spasticity is a condition characterized by continuous muscle contraction, resulting in stiffness or tightness that can interfere with normal movement and speech. Tizanidine helps alleviate these symptoms, providing relief to those suffering from various conditions that cause muscle spasms.

Primary Uses of Tizanidine

• Treatment of spasticity
• Temporary relaxation of muscle tone
• Relief from muscle spasms

While these are the primary uses of tizanidine, it’s important to note that healthcare providers may prescribe this medication for other purposes not listed in the standard medication guide. Always consult with your doctor about the specific reason for your tizanidine prescription.

Tizanidine Dosage: Finding the Right Balance

When it comes to tizanidine dosage, precision is key. The recommended starting dose is typically 2 mg every 6 to 8 hours, with a maximum of 3 doses in a 24-hour period. However, it’s crucial to understand that dosage can vary based on individual needs and medical conditions.

What’s the maximum amount of tizanidine that can be taken in a day? Healthcare providers advise not to exceed 36 mg of tizanidine in a 24-hour period. This limit is in place to prevent potential liver damage, which can occur with excessive use of the medication.

Dosage Guidelines

1. Start with 2 mg every 6-8 hours
2. Do not exceed 3 doses in 24 hours
3. Maximum daily dose: 36 mg
4. Adjust dosage under medical supervision

It’s important to follow your doctor’s instructions carefully regarding dosage. Any changes in how you take tizanidine, including switching between tablets and capsules or altering your eating habits in relation to taking the medication, can affect its efficacy and side effects. Always consult your healthcare provider before making any changes to your tizanidine regimen.

The Mechanism of Action: How Tizanidine Works

Understanding how tizanidine works in the body can help patients appreciate its effects and potential side effects. But how exactly does this muscle relaxant function?

Tizanidine primarily works by acting on the central nervous system. It is an alpha-2 adrenergic agonist, which means it stimulates certain receptors in the brain and spinal cord. This stimulation leads to a reduction in the release of excitatory neurotransmitters, particularly those responsible for muscle contraction and spasticity.

Key Points in Tizanidine’s Mechanism of Action

• Acts as an alpha-2 adrenergic agonist
• Reduces release of excitatory neurotransmitters
• Decreases muscle contraction and spasticity
• Effects are most noticeable 1-3 hours after ingestion

By understanding this mechanism, it becomes clear why tizanidine is effective for short-term relief of muscle spasticity. Its effects are most pronounced between 1 and 3 hours after taking the medication, which is why it’s often prescribed for specific daily activities that require relief from muscle spasms.

Potential Side Effects and Precautions

While tizanidine can be highly effective in managing muscle spasticity, it’s important to be aware of potential side effects and necessary precautions. What are some common side effects of tizanidine?

Common side effects may include:

• Drowsiness or dizziness
• Dry mouth
• Weakness or fatigue
• Urinary tract infection
• Constipation or diarrhea
• Increased muscle weakness

In rare cases, more serious side effects can occur. These may include liver damage, hallucinations, or severe allergic reactions. It’s crucial to seek immediate medical attention if you experience any severe or unusual symptoms while taking tizanidine.

Important Precautions

What precautions should be taken when using tizanidine? Here are some key points to consider:

1. Avoid alcohol consumption while taking tizanidine, as it can increase side effects.
2. Do not use tizanidine when you need muscle tone for safe balance and movement.
3. Inform your doctor about any liver or kidney disease, as these conditions may affect how your body processes the medication.
4. Be cautious when driving or operating machinery, as tizanidine can cause drowsiness.
5. Avoid abrupt discontinuation of tizanidine after long-term use, as it may lead to withdrawal symptoms.

It’s also important to note that tizanidine can interact with other medications. Always inform your healthcare provider about all medications, supplements, and herbal products you’re taking to avoid potential drug interactions.

Tizanidine vs. Other Muscle Relaxants: A Comparative Analysis

How does tizanidine compare to other muscle relaxants on the market? While tizanidine is effective for treating muscle spasticity, it’s not the only option available. Other commonly prescribed muscle relaxants include baclofen, cyclobenzaprine, and methocarbamol.

Each of these medications works differently and may be more suitable for certain conditions or patients. For example:

• Baclofen is often used for spasticity related to spinal cord injuries or multiple sclerosis
• Cyclobenzaprine is typically prescribed for short-term relief of muscle spasms associated with acute musculoskeletal conditions
• Methocarbamol is used for muscle spasms caused by acute, painful musculoskeletal conditions

Tizanidine stands out due to its short-acting nature and its specific mechanism of action as an alpha-2 adrenergic agonist. This makes it particularly useful for managing spasticity in conditions like multiple sclerosis, spinal cord injury, or stroke.

Comparing Side Effect Profiles

When comparing tizanidine to other muscle relaxants, it’s important to consider the side effect profiles. While all muscle relaxants can cause drowsiness and dizziness, tizanidine may have a lower risk of causing muscle weakness compared to some other options. However, it does carry a risk of liver toxicity, which requires careful monitoring.

Ultimately, the choice between tizanidine and other muscle relaxants depends on various factors, including the specific condition being treated, the patient’s overall health, and potential drug interactions. A healthcare provider can help determine the most appropriate muscle relaxant based on individual circumstances.

Managing Tizanidine Use: Tips for Patients

For patients prescribed tizanidine, proper management of the medication is crucial for maximizing its benefits while minimizing potential risks. What are some key tips for patients taking tizanidine?

1. Consistency is key: Take tizanidine at the same times each day and in the same way (with or without food) to maintain consistent blood levels of the medication.
2. Monitor for side effects: Keep track of any side effects you experience and report them to your healthcare provider.
3. Regular check-ups: Attend all scheduled appointments with your doctor, especially for liver function tests if you’re on long-term tizanidine therapy.
4. Avoid sudden changes: Don’t stop taking tizanidine abruptly without consulting your doctor, as this can lead to withdrawal symptoms.
5. Be cautious with other medications: Always inform your healthcare providers about your tizanidine use before starting any new medications.

Managing Drowsiness

One of the most common side effects of tizanidine is drowsiness. How can patients manage this side effect effectively?

• Take tizanidine at bedtime if drowsiness is particularly bothersome
• Avoid driving or operating machinery until you know how tizanidine affects you
• Discuss with your doctor about adjusting the dosage or timing of doses if drowsiness is severe
• Avoid alcohol and other central nervous system depressants while taking tizanidine

Remember, everyone responds differently to medications. What works for one person may not work for another. It’s essential to maintain open communication with your healthcare provider to ensure that your tizanidine regimen is optimized for your specific needs.

Tizanidine in Special Populations: Considerations and Cautions

While tizanidine can be an effective treatment for muscle spasticity in many patients, special considerations must be taken into account for certain populations. How does tizanidine use differ in these special groups?

Elderly Patients

Older adults may be more sensitive to the effects of tizanidine, particularly its sedative properties. They may also be at increased risk of falls due to the muscle-relaxing effects of the medication. For these reasons, lower starting doses are often recommended for elderly patients, with careful monitoring for side effects.

Patients with Liver or Kidney Disease

Tizanidine is primarily metabolized in the liver and excreted by the kidneys. Patients with liver or kidney disease may have impaired ability to process and eliminate the drug, potentially leading to increased blood levels and side effects. Dose adjustments and close monitoring are typically necessary for these patients.

Pregnant and Breastfeeding Women

The safety of tizanidine during pregnancy and breastfeeding has not been firmly established. While some studies suggest it may be safe, the potential risks to the fetus or infant are not fully known. Women who are pregnant, planning to become pregnant, or breastfeeding should discuss the risks and benefits of tizanidine use with their healthcare provider.

Children and Adolescents

Tizanidine is not typically recommended for use in children under 18 years of age, as its safety and efficacy have not been established in this population. However, in some cases, it may be prescribed off-label for pediatric patients with certain conditions causing muscle spasticity.

For all these special populations, the key is individualized care. Healthcare providers must carefully weigh the potential benefits of tizanidine against the risks, considering factors such as the severity of spasticity, alternative treatment options, and the overall health status of the patient.

The Future of Muscle Spasticity Treatment: Beyond Tizanidine

While tizanidine remains a valuable tool in the management of muscle spasticity, ongoing research continues to explore new treatment options and refine existing therapies. What does the future hold for muscle spasticity treatment?

Emerging Therapies

Several promising avenues are being explored in the realm of muscle spasticity treatment:

• Targeted Drug Delivery: Intrathecal baclofen pumps deliver medication directly to the spinal cord, potentially reducing systemic side effects.
• Neurostimulation: Techniques like spinal cord stimulation and transcranial magnetic stimulation show promise in managing spasticity.
• Botulinum Toxin: While already in use, research continues to refine the application of botulinum toxin injections for localized spasticity.
• Cannabis-based Treatments: Some studies suggest that cannabinoids may have potential in managing spasticity, particularly in multiple sclerosis.

Personalized Medicine Approaches

The future of spasticity treatment is likely to involve more personalized approaches. This may include genetic testing to predict drug responses and side effects, allowing for more tailored treatment plans. Additionally, combination therapies that leverage the strengths of different treatment modalities may become more commonplace.

Rehabilitation Technologies

Advances in rehabilitation technologies are also playing a role in spasticity management. Robotic-assisted therapy, virtual reality-based rehabilitation, and wearable technologies for monitoring and managing spasticity are all areas of active research and development.

While these advancements hold promise, it’s important to note that tizanidine and other current treatments will likely continue to play a significant role in spasticity management. The goal of future research is not necessarily to replace these medications, but to provide a broader range of options to better meet the diverse needs of patients with spasticity.

As research progresses, patients and healthcare providers can look forward to an expanding toolkit for managing muscle spasticity, potentially offering more effective and personalized treatment options. However, as with any medical advancement, rigorous testing and careful consideration of risks and benefits will be crucial in bringing these new therapies to patients.

Tizanidine Uses, Dosage, Side Effects

Generic name: tizanidine [ tye-ZAN-i-deen ]
Brand name: Zanaflex
Drug class: Skeletal muscle relaxants

Medically reviewed by Sanjai Sinha, MD. Last updated on Jan 10, 2022.

What is tizanidine?

Tizanidine is a short-acting muscle relaxer. It works by blocking nerve impulses (pain sensations) that are sent to your brain.

Tizanidine is used to treat spasticity by temporarily relaxing muscle tone.

Tizanidine may also be used for purposes not listed in this medication guide.

Warnings

Tizanidine is a short-acting medication that should be taken only for daily activities that require relief from muscle spasticity.

You should not take tizanidine if you are also taking fluvoxamine (Luvox) or ciprofloxacin (Cipro).

Do not use tizanidine at a time when you need muscle tone for safe balance and movement during certain activities. In some situations, it may endanger your physical safety to be in a state of reduced muscle tone.

Switching between tablets and capsules, or changing the way you take it with regard to eating, can cause an increase in side effects or a decrease in therapeutic effect. Follow your doctor’s instructions carefully. After making any changes in how you take tizanidine, contact your doctor if you notice any change in how well the medicine works or if it causes increased side effects.

The recommended starting dose of tizanidine is 2 mg every 6 to 8 hours, up to a maximum of 3 doses in 24 hours. Do not take more than 36 mg of tizanidine in a 24-hour period. Too much of this medicine can damage your liver. Cold or allergy medicine, narcotic pain medicine, sleeping pills, other muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by tizanidine.

Avoid drinking alcohol. It can increase some of the side effects of this medicine.

Before taking this medicine

You should not use tizanidine if you are allergic to it, or if:

To make sure tizanidine is safe for you, tell your doctor if you have ever had:

• liver disease;

• kidney disease; or

• low blood pressure.

It is not known whether tizanidine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.

How should I take tizanidine?

Take tizanidine exactly as it was prescribed for you. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Tizanidine is usually taken up to 3 times in one day, starting at 2mg per dose. Allow 6 to 8 hours to pass between doses. Do not take more than 36 mg in a 24-hour period. Too much of this medicine can damage your liver.

You may take tizanidine with or without food, but take it the same way each time. Switching between taking with food and taking it without food can make the medicine less effective or cause increased side effects.

Switching between tablets and capsules may cause changes in side effects or how well the medicine works.

If you make any changes in how you take tizanidine, tell your doctor if you notice any change in side effects or in how well the medicine works.

Tizanidine is a short-acting medication, and its effects will be most noticeable between 1 and 3 hours after you take it. You should take this medicine only for daily activities that require relief from muscle spasms.

You will need frequent blood tests to check your liver function.

If you stop using this medicine suddenly after long-term use, you may have withdrawal symptoms such as dizziness, fast heartbeats, tremors, and anxiety. Ask your doctor how to safely stop using this medicine.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include weakness, drowsiness, confusion, slow heart rate, shallow breathing, feeling light-headed, or fainting.

What to avoid

Do not use tizanidine at a time when you need muscle tone for safe balance and movement during certain activities. In some situations, it may be dangerous for you to have reduced muscle tone.

Drinking alcohol with this medicine can cause side effects.

Avoid driving or hazardous activity until you know how this medicine will affect you. Your reactions could be impaired. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Tizanidine side effects

Get emergency medical help if you have signs of an allergic reaction to tizanidine: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;

• weak or shallow breathing;

• confusion, hallucinations; or

• pain or burning when you urinate.

Common tizanidine side effects may include:

• drowsiness, dizziness, weakness;

• feeling nervous;

• blurred vision;

• flu-like symptoms;

• dry mouth, trouble speaking;

• abnormal liver function tests;

• runny nose, sore throat;

• urination problems, painful urination;

• vomiting, constipation; or

• uncontrolled muscle movements.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect tizanidine?

Taking tizanidine with other drugs that make you sleepy or slow your breathing can cause dangerous side effects or death. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety or seizures.

Tell your doctor about all your other medicines, especially:

• acyclovir;

• ticlopidine;

• zileuton;

• birth control pills;

• an antibiotic – ciprofloxacin, levofloxacin, moxifloxacin, or ofloxacin;

• blood pressure medicine – clonidine, guanfacine, methyldopa;

• heart rhythm medicine – amiodarone, mexiletine, propafenone, verapamil; or

• stomach acid medicine – cimetidine, famotidine.

This list is not complete. Other drugs may interact with tizanidine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Popular FAQ

The maximum effect of tizanidine occurs about 1 hour to 2 hours after taking a dose. It wears off in about 3 to 6 hours after taking it. Tizanidine is typically given no more than 3 times a day.

Tizanidine is not listed as a controlled substance by the U.S. Drug Enforcement Administration (DEA). Abuse potential has not been evaluated in human studies.

Tizanidine can cause sleepiness, but it has not been approved by the U.S. Food and Drug Administration (FDA) to treat sleep disorders. Tizanidine is a skeletal muscle relaxant. It is approved by the FDA to help relieve muscle spasms.

Tizanidine is known to cause low blood pressure. In some cases, it may cause low blood pressure that is so low that you could faint or pass out. The chances of fainting can be lowered if your doctor raises the dose of tizanidine very slowly. You may also have to be careful when you move from a sitting position to a standing position. In clinical trials, the most common side effects of tizanidine were dry mouth, sleepiness, dizziness and asthenia (defined as weakness, fatigue and/or tiredness).

Tizanidine normally starts working 1 to 2 hours after taking it. It wears off about 3 hours to 6 hours after taking it. Tizanidine can be taken up to 3 times a day to help relieve muscle spasms.

Tizanidine may be addictive, but it has not been evaluated in human studies. Withdrawal symptoms have been reported after abruptly stopping tizanidine, but abuse of other medications concomitantly was suspected in these cases. Dosing should be tapered off to avoid possible withdrawal symptoms.

Tizanidine is not known to cause weight gain. In clinical trials, the most common side effects of tizanidine were dry mouth, sleepiness, dizziness and asthenia (defined as weakness, fatigue and/or tiredness).

More about tizanidine

• Check interactions
• Compare alternatives
• Pricing & coupons
• Reviews (371)
• Drug images
• Side effects
• Dosage information
• Patient tips
• During pregnancy
• Support group
• Drug class: skeletal muscle relaxants
• En español

Patient resources

Other brands

Zanaflex

Professional resources

• Prescribing Information

Related treatment guides

• Muscle Spasm
• Cluster Headaches

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use tizanidine only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Copyright 1996-2023 Cerner Multum, Inc. Version: 4.01.

Tizanidine Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Uses

This medication is used to treat muscle spasms caused by certain conditions (such as multiple sclerosis, spinal cord injury). It works by helping to relax the muscles.

How to use Tizanidine HCL

Take this medication by mouth as directed by your doctor, usually every 6 to 8 hours.

The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor’s instructions carefully. Do not take more than 36 milligrams a day or more than 3 doses in a 24-hour period.

Your body will absorb this medication differently depending on whether you take it as a tablet or capsule, whether you take it with food or on an empty stomach, or if you sprinkle the contents of the capsule on food. Be sure to discuss with your doctor how to take this medication to determine the best way to take your dose, especially when changes to your dose are being considered or if your doctor prescribes a different form of tizanidine (such as tablet or capsule).

If you suddenly stop using this medication, you may have withdrawal symptoms (such as anxiety, tremor, increased blood pressure/heart rate/muscle tenseness). To help prevent withdrawal, your doctor may lower your dose slowly. Withdrawal is more likely if you have used tizanidine for a long time or in high doses. Tell your doctor or pharmacist right away if you have withdrawal.

Tell your doctor if your condition does not improve or if it worsens.

Side Effects

Dry mouth, drowsiness, dizziness, lightheadedness, constipation, weakness, and tiredness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

To relieve dry mouth, suck (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: fainting, mental/mood changes (such as hallucinations), slow/irregular heartbeat, vision changes (such as blurred vision).

Tizanidine has rarely caused very serious (rarely fatal) liver disease. Tell your doctor right away if you develop symptoms of liver disease, including: nausea/vomiting that doesn’t stop, severe stomach/abdominal pain, dark urine, yellowing eyes/skin.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking tizanidine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: low blood pressure, kidney disease, liver disease.

This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the side effects of this drug, especially dizziness and drowsiness. These effects can increase the risk of falling.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug include: certain drugs to treat high blood pressure (alpha agonists such as clonidine, methyldopa).

Other medications can affect the removal of tizanidine from your body, which may affect how tizanidine works. Examples include birth control pills, ciprofloxacin, fluvoxamine, viloxazine, among others.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, marijuana (cannabis), antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), other muscle relaxants, and opioid pain relievers (such as codeine).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

Does Tizanidine HCL interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness/drowsiness, confusion, slow/shallow breathing, fainting.

Do not share this medication with others.

Lab and/or medical tests (such as blood pressure, liver function) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Images

tizanidine 2 mg tablet

Color: whiteShape: roundImprint: U 168

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg tablet

Color: whiteShape: roundImprint: 1 1 04

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg tablet

Color: whiteShape: roundImprint: APO TI-4

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg tablet

Color: whiteShape: ovalImprint: R180

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg tablet

Color: whiteShape: ovalImprint: R179

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg tablet

Color: whiteShape: roundImprint: U 169

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg tablet

Color: whiteShape: roundImprint: APO TI-2

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg tablet

Color: whiteShape: roundImprint: 503

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg tablet

Color: whiteShape: roundImprint: E 44

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg tablet

Color: whiteShape: roundImprint: 1105

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg capsule

Color: light blueShape: oblongImprint: 1111

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg capsule

Color: white,blueShape: oblongImprint: 4 MG

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg capsule

Color: light blueShape: oblongImprint: 2 MG

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 6 mg capsule

Color: blueShape: oblongImprint: 6 MG

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg tablet

Color: whiteShape: roundImprint: 502

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg capsule

Color: light blueShape: oblongImprint: 2MG Tiza

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg capsule

Color: blueShape: oblongImprint: APO T2

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 6 mg capsule

Color: light blue,whiteShape: oblongImprint: C 672

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg capsule

Color: light blueShape: oblongImprint: C 671

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg capsule

Color: white,blueShape: oblongImprint: C 670

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 6 mg capsule

Color: blueShape: oblongImprint: APO T6

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg capsule

Color: white,blue-greenShape: oblongImprint: APO T4

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 6 mg capsule

Color: blueShape: oblongImprint: ING 226 ING 226

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg capsule

Color: light blue,whiteShape: oblongImprint: ING 225 ING 225

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg tablet

Color: whiteShape: roundImprint: M 724

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg capsule

Color: light blueShape: oblongImprint: ING 224 ING 224

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 6 mg capsule

Color: violetShape: oblongImprint: 1113

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg capsule

Color: white,violetShape: oblongImprint: 1112

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 4 mg capsule

Color: white,blueShape: oblongImprint: 4MG Tiza

This medicine is a white, round, scored, tablet imprinted with “U 168”.

tizanidine 2 mg tablet

Color: whiteShape: roundImprint: M 722

This medicine is a white, round, scored, tablet imprinted with “U 168”.

Next

Save up to 80% on your prescriptions.

Available coupons

Save up to 80% on your prescription with WebMDRx

Drug Survey

Are you currently using Tizanidine HCL?

This survey is being conducted by the WebMD marketing sciences department.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, except as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

The use of tizanidine (Sirdalud) in the treatment of pain and spasm | Danilov A.B.

The drug tizanidin (Sirdalud) belongs to the centrally acting muscle relaxants (α2-adrenergic agonists) and implements its effect at the spinal and supraspinal levels [4]. By stimulating presynaptic α2 receptors, it inhibits the release of excitatory amino acids that stimulate NMDA receptors. This leads to the suppression of the transmission of excitation through the polysynaptic reflexes of the spinal cord. The drug mainly inhibits the polysynaptic reflexes of the spinal cord responsible for muscle hypertonicity, which causes a decrease in the increased tone of the flexor and extensor muscles and a decrease in painful muscle spasms. In addition to muscle relaxant properties, tizanidine also has a central, moderately pronounced analgesic effect (by reducing the release of excitatory neurotransmitters in the brain at the level of the locus coeruleus). In animal studies, it has been shown that tizanidine (Sirdalud) can realize its effect through a decrease in central sensitization [11]. These properties of tizanidine allow it to be used both as a means to reduce muscle spasm, and for the treatment of a number of pain syndromes (associated with muscle spasm).

Tizanidin (Sirdalud)
for pain syndromes
Monotherapy with tizanidine (Sirdalud) for pain syndromes. Muscular tonic and myofascial pain syndromes are very often the main reason for patients to seek medical attention. In the treatment of muscular-tonic pain, the central place belongs to local influences aimed at relaxing the muscle (massage, applications of warming ointments, gels, wet compresses, etc.), and in the case of myofascial pain syndrome, on the destruction of trigger points using post-isometric relaxation, the introduction of dry needles or anesthetic into the trigger zone. The terms of therapy are significantly reduced with effective anesthesia of the patient. A common method of pain relief for myofascial pain is also the use of non-steroidal anti-inflammatory drugs (NSAIDs).
Muscle relaxants can be of great help in the treatment of muscular-tonic and myofascial pain syndromes by reducing the intensity of pain, reducing painful muscle tension, and improving motor activity. The use of muscle relaxants is justified by the recognition of the important role of muscle spasm in the pathogenesis of pain in the lower back. Pain of various origins (due to damage to the intervertebral discs, facet joints of the spine, the muscles themselves and other causes) increases the activity of the motor neurons of the spinal cord, which leads to muscle spasm, which in turn plays a significant role in maintaining the pain itself. Pathologically increased muscle tone has various mechanisms for increasing pain: direct irritation of muscle pain receptors, deterioration of blood supply to the muscles, which leads to the formation of a vicious circle leading to increased muscle spasm and accompanying pain. Muscle relaxants break the vicious circle of “pain – muscle spasm – pain” and, as a result, can accelerate the recovery period [6]. In European guidelines for the treatment of acute pain in the lower back, tizanidine, dantrolene, diazepam, baclofen are noted as effective muscle relaxants [19]. In our country, of these drugs, tizanidine (Sirdalud) is most commonly used [6].
The effective daily dose range of tizanidine (Sirdalud) for pain syndromes is 2–12 mg (the optimal dose is 6–8 mg/day). For mild pain syndromes, the appointment of tizanidine (Sirdalud) can be limited to taking the drug at night at a dose of 2-4 mg until the pain stops (usually 5-7 days). With a moderately severe pain syndrome, it is also better to prescribe the first dose at night at a dose of 2–4 mg (the patient will “oversleep” the side effects), then gradually increase the dose to 6–8 mg / day. In severe cases, an additional 2–4 mg of tizanidine (Sirdalud) at night can be added. A positive effect, as a rule, is already noted on the 3rd day of taking the drug. In chronic pain syndromes, a course of therapy is usually carried out lasting 2-4 weeks, adjusting the duration of treatment and the dose of the drug depending on the efficacy / tolerability.
It should be noted that for mild to moderate pain associated with muscle spasm (eg, acute pain in the neck or lower back), it may be sufficient to prescribe tizanidine (Sirdalud) as monotherapy.
The effectiveness of tizanidine monotherapy (Sirdalud) has been confirmed in many studies, incl. and in a multicenter study that included 2251 patients with acute pain caused by muscle spasm in the lower back, neck, or shoulder. 89% of patients rated the treatment outcome as “good” or “very good”. The study also noted a very good tolerability of the drug (90% of patients reported tolerability as “good” or “very good”). These results allowed the authors to recommend tizanidine as the drug of choice among muscle relaxants for the treatment of pain associated with muscle spasm [13].
Combination of tizanidine (Sirdalud) with NSAIDs. With more severe pain, or when it is based on inflammatory changes, it is advisable to use tizanidine and NSAIDs together. Studies show that the use of tizanidine potentiates the effect of NSAIDs [9,16]. In addition, taking tizanidine (Sirdalud) has a gastroprotective effect, which is associated with its adrenergic activity and antispasmodic effect. Tizanidin (Sirdalud) reduces basal and induced acid secretion in the stomach, eliminates the imbalance of glycoproteins in the gastric mucosa and gastric secretions [11,16].
In experimental studies, the use of tizanidine demonstrated a significant decrease in the ulcerogenic effect of acetylsalicylic acid, indomethacin, meloxicam, nimesulide and naproxen. The gastroprotective activity of tizanidine has also been proven in clinical studies. In patients receiving the combination of ibuprofen and tizanidine, the frequency of gastrointestinal side effects, including bleeding, was significantly (p = 0.002) lower than in patients receiving the combination of ibuprofen and placebo [9]. Similar results were obtained when comparing the combination of diclofenac and tizanidine with the combination of diclofenac and placebo in a multicenter (12 centers), prospective, double-blind, placebo-controlled, randomized clinical trial conducted in 6 countries of the Asia-Pacific region and including 405 participants [16]. Gastropathy was reported in 12% of patients treated with a combination of diclofenac and tizanidine versus 32% of patients treated with diclofenac in combination with placebo (p<0.001). The frequency of positive fecal occult blood test results was 5% in the main group compared to 11% in the control group.
The gastroprotective effect of Sirdalud is especially important for the management of patients with chronic pain syndromes who take NSAIDs for a long period of time (for rheumatological diseases), which often leads to the development of erosive gastritis and gastric and duodenal ulcers [1].
Combination of tizanidine (Sirdalud) with antidepressants and anticonvulsants. The management of chronic pain is more complex than the management of acute pain and requires an integrated approach. The use of muscle relaxants here is only a component of treatment and should be justified by the presence of a therapeutic target – muscle spasm. In this regard, the patient’s expectations regarding the effect of a muscle relaxant should be correctly formed: the use of tizanidine (Sirdalud) can reduce pain, facilitate the patient’s movements, but will not stop the pain completely, because. in chronic pain, the muscle component is not the leading one.
In the treatment of chronic pain syndromes, anticonvulsants, antidepressants are used, so it is important to consider how tizanidine (Sirdalud) interacts with these drugs. There are works that show that tizanidine (Sirdalud) potentiates the action of tricyclic antidepressants (amitriptyline) [10]. At the same time, it must be remembered that tizanidine (Sirdalud) cannot be combined with fluvoxamine, an antidepressant from the SSRI group. Simultaneous administration of tizanidine (Sirdalud) and fluvoxamine can lead to a significant decrease in blood pressure and cause complications from the central nervous system.
Thus, due to high efficiency and minor side effects, a number of domestic and foreign experts consider tizanidine (Sirdalud) as the drug of choice for the treatment of acute and subacute myofascial pain in monotherapy and as the drug of first choice for the treatment of chronic myofascial syndrome in combination with other drugs [2 ,13].
Tizanidin (Sirdalud)
in neurological practice
Disturbances in muscle tone, associated pain syndromes, restrictions on motor functions, secondary changes in joints and muscles are part of the clinical manifestations of many diseases of the nervous system. As a rule, the problem of increasing muscle tone – hypertonicity or spasticity – acquires clinical significance [8]. However, the causes of hypertonicity and the mechanisms underlying it may be different, and therefore the treatment of spasticity requires differentiated approaches to treatment.
The use of tizanidine (Sirdalud) is most widely used in the treatment of spasticity in traumatic injuries of the brain and spinal cord, multiple sclerosis, and stroke. With spasticity associated with dystonic disorders, parkinsonism, it is more appropriate to use other drugs (for example, clonazepam, diazepam).
Spasticity leads to significant functional disorders and impaired quality of life of the patient. However, it should be remembered that spasticity itself does not always require treatment. For example, in some patients with severe paresis, the presence of spasticity in the muscles that anatomically oppose gravity (anti-gravity muscles) can make standing and walking easier. In addition, the presence of increased muscle tone can prevent the development of muscle atrophy, soft tissue edema and osteoporosis, as well as reduce the risk of thrombosis of the lower extremities. Indications for the treatment of spasticity are only those cases when, due to increased tone, the “functioning, positioning or comfort” of the patient is disturbed.
The use of tizanidine (Sirdalud) in stroke. In stroke, the main objectives of treatment are not only to reduce the severity of spasticity, but also to improve the functionality of paretic limbs, reduce pain and discomfort associated with high muscle tone, and facilitate care for a paralyzed patient.
The most effective means in the fight against spasticity are exercise therapy and physiotherapy, especially at an early stage. In cases where patients with post-stroke limb paresis have local spasticity, local administration of botulinum toxin preparations can be used. A significant contribution to the treatment of spasticity can be made by the use of anti-spastic drugs (muscle relaxants) for oral administration. The use of muscle relaxants can reduce muscle tone, improve motor functions, facilitate care for an immobilized patient, relieve painful muscle spasms, enhance the effect of physiotherapy and, as a result, prevent the development of contractures. In our country, tizanidine, baclofen, tolperisone, diazepam are used to treat post-stroke spasticity.
An analysis of 20 studies comparing the use of various antispastic agents in a variety of neurological diseases accompanied by spasticity showed that tizanidine, baclofen and diazepam are approximately equally able to reduce spasticity, but tizanidine (Sirdalud) is more effective than other antispastic agents in reducing clonus [14] . Unlike baclofen, tizanidin (Sirdalud) does not cause a decrease in muscle strength with a decrease in spasticity (which is very important for improving the functionality of the limb), it is better tolerated by patients than baclofen and diazepam (when using it, patients are less likely to stop treatment due to side effects) [14,15,20]. Among the side effects identified during the study of tizanidine in patients with post-stroke spasticity, conducted by Gelber (2001), the most common side effects were drowsiness, weakness, dizziness, dry mouth, orthostatic hypotension. These phenomena took place with the abolition or reduction of the dose of the drug. At the same time, no serious side effects were noted during treatment with tizanidine [Gelber, 2001], which allowed the authors to conclude that it is highly safe.
Authors who have conducted studies on the clinical effects of tizanidine (Sirdalud) and many clinicians agree that among muscle relaxants, tizanidine (Sirdalud) is the drug of first choice for the treatment of post-stroke spasticity [7,12,14,15,20].
For the treatment of spasticity due to neurological diseases, higher doses of tizanidine (Sirdalud) are usually used than for the treatment of pain syndromes. Usually the optimal therapeutic effect is achieved with a daily dose of 12 to 24 mg (effective dose range is 2-36 mg). However, given the dose-dependent increase in the risk of side effects with increasing doses of the drug, treatment should be started with small (2-6 mg / day) doses, then gradually increase the dose until a therapeutic effect is achieved, observing individual tolerability (usually 2-6 mg / day). 4 mg every 3–7 days divided into 3 doses per day). If side effects occur, you can temporarily stop increasing the dose (if you do not increase the dose, in many cases the side effects disappear after a few days) and continue increasing the dose after the patient gets used to the drug. This allows, firstly, to select the most effective minimum dose of the drug for a particular patient (in some patients (due to individual variability), a sufficient therapeutic effect may occur when taking smaller doses than recommended standards), as well as to relieve unnecessary suffering of patients with individual poor tolerance to tizanidine (in patients with poor tolerance to tizanidine, side effects appear already at a dose of 2-4 mg / day). Dose titration usually takes 2-4 weeks. The duration of treatment is set individually (from several weeks to several months) [8].
The use of prolonged forms of tizanidine (Sirdalud MR). For long-term use, a dosage form of tizanidine in the form of modified-release capsules (Sirdalud MR), which is available in a dose of 6 mg, is convenient. Clinical experience shows that for most patients the optimal dose is 12 mg / day. (2 capsules), in rare cases, it may be necessary to increase the daily dose to 24 mg. Treatment also begins with a minimum dose of 6 mg (1 capsule), if necessary, gradually increasing the dose by 6 mg (1 capsule) at intervals of 3-7 days.
The use of tizanidine (Sirdalud) in traumatic brain injury. Among muscle relaxants, tizanidine (Sirdalud) is the most commonly used drug for the treatment of spasticity associated with traumatic brain injury [5]. The reasons for prescribing, dose selection tactics and warnings are the same as in the treatment of post-stroke spasticity.
The use of tizanidine (Sirdalud) in multiple sclerosis and spinal injury. Restriction of mobility in patients with multiple sclerosis is associated with a significant increase in spastic muscle tone, mainly in the lower extremities. The basis of the treatment of muscle tone disorders are special exercises that should be performed under the supervision of a specialist in physical therapy. Drug therapy plays a complementary role. Among the drugs used to treat spasticity are tolperisone, baclofen, tizanidine, diazepam. Drug treatment of spastic tone should be individual, controlled by the doctor and the patient himself. This is because most anti-tonus drugs increase the weakness of the paralyzed limbs and may worsen the patient’s condition. In this regard, the dose of the antispastic drug should be gradually increased from the minimum to the optimum, when spasticity decreases, but there is no increase in weakness. Sirdalud in this regard is more preferable than baclofen and diazepam (when using tizanidine (Sirdalud), muscle weakness develops less often; due to excessive relaxation of the sphincters of the bladder when using baclofen, patients often complain of an increase in pelvic disorders; the use of diazepam is associated with a greater frequency development of side effects, drug dependence) [3,17]. Sirdalud is more effective than other muscle relaxants against clonuses [14].
The optimal daily dose of Sirdalud for the treatment of spasticity in multiple sclerosis is 6–8 mg (maximum daily dose is 36 mg). It is also necessary to start treatment with the minimum dose, the step of increasing the dose is 2 mg [3].
In patients with spasticity due to spinal injury, tizanidine (Sirdalud) and baclofen are most commonly used, and diazepam is used to relieve painful muscle spasms. Treatment begins with a minimum dose (4-6 mg Sirdalud), which is gradually brought to a therapeutic dose over several days or weeks, trying to avoid unwanted side effects (muscle weakness and sedation). Baclofen is effective mainly when administered intrathecally; when administered orally, tizanidine (Sirdalud) gives a more pronounced positive effect and is better tolerated by patients than baclofen [18].
For other types of spasticity encountered in neurological practice (with parkinsonism, torsion dystonia, torticollis, ALS), the use of tizanidine (Sirdalud) is not justified. In these cases, the use of clonazepam and diazepam is more appropriate. These drugs have a higher likelihood of side effects, but their antispasmodic effect is more pronounced in these disorders.
Treatment Optimization
when using tizanidine
(Sirdaluda)
A sufficiently wide range of effective doses of tizanidine (Sirdalud) (from 2 to 36 mg / day) allows the use of the drug for short and long courses of treatment of pain syndromes and spasticity as monotherapy or in combination with other drugs. To improve clinical performance, the following recommendations for the practical use of tizanidine (Sirdalud) may be helpful.
Start treatment with small doses of the drug. The development of side effects with the use of tizanidine (Sirdalud) is dose-dependent (for example, the likelihood of side effects with a dose of 12-24 mg is 2 times higher than with a dose of 6-12 mg). At the same time, a sufficient therapeutic effect can sometimes be achieved at lower doses than recommended in the treatment standards. In this regard, it is recommended to start treatment with a minimum dose (2-4 mg), then gradually increase it, observing individual tolerance.
Gradual withdrawal of the drug. After prolonged use of tizanidine (Sirdalud), especially in large doses, it is necessary to gradually discontinue the drug, because. abrupt withdrawal can cause the development of muscle weakness (this is also characteristic of other muscle relaxants).
The use of tizanidin (Sirdalud) to normalize sleep
Side effects of tizanidine (Sirdalud) include increased drowsiness. Therefore, patients who experience drowsiness while taking tizanidine (Sirdalud) should avoid all activities that require increased concentration and responsiveness. At the same time, many patients, especially those with chronic pain syndromes, have disturbed sleep. This side effect of tizanidine (Sirdalud) can be used therapeutically by prescribing the drug at night to improve the patient’s sleep. Given that the effect of tizanidine (Sirdalud) is short-lived, some doctors, in order to maintain the patient’s social activity, prescribe the drug only at night or distribute the main daily dose of the drug in the afternoon and at night. This allows the patient to maintain social activity in the morning (work, drive a car), and in the evening helps to fall asleep, as well as “sleep” other side effects.
Use of tizanidine (Sirdalud) as an antihypertensive
funds
One of the side effects when using tizanidine (Sirdalud) is a moderate decrease in blood pressure. Simultaneous use with antihypertensive agents may enhance the antihypertensive effect. If long-term use of tizanidine (Sirdalud) is necessary (for example, in the treatment of post-stroke spasticity), the hypotensive effect of tizanidine (Sirdalud) can be used to reduce the dose or stop taking blood pressure-lowering drugs if the patient is receiving antihypertensive therapy.
Conclusion
Tizanidine is an effective drug both in the treatment of spasticity in a number of neurological disorders, and for the treatment of a wide range of pain syndromes associated with increased muscle tone. However, the success of the treatment in each particular case depends not only on the correct choice of a particular drug in terms of the symptoms described in the instructions for use and evidence-based studies on the effectiveness of the drug, but also on how the attending physician manages to correlate the features of pharmacokinetic properties of the drug with individual clinical manifestations of the disease in this (specific) patient.

Literature
1. Badokin V.V. The use of Sirdalud in rheumatological practice // Rus. honey. magazine. – 2005. – T. 13, No. 24. – S. 1588-1589.
2. Vorobieva O.V. Possibilities of alpha2-adrenergic agonists in the treatment of myofascial pain // Rus. honey. magazine – 2007. – No. 5. – C. 445–448.
3. Gusev E.I., Boyko A.N. Multiple sclerosis: from new knowledge to new methods of treatment // Ros. honey. magazine. – 2001. – No. 1. – P. 4–10.
4. Danilov A.B. Possibilities of using tizanidine (Sirdalud) in clinical practice. Literature review // RMJ. – 2010. – No. 1. – P. 4–10.
5. Parfenov V.A. Management of patients with spasticity // Rus. honey. magazine. – 2004. – T. 12, No. 10.
6. Parfenov V.A. Diagnosis and treatment of acute pain in the lower back // Rus. honey. magazine – 2007. – T 15 No. 6.
7. Parfenov V.A. Post-stroke spasticity and its treatment // Rus. honey. magazine – 2006. – T. 14, No. 9.
8. Shirokov, E.A. Sirdalud: areas of clinical application // Rus. honey. magazine – 2004. – No. 14. – C. 874–875.
9. Berry H., Hutchinson D.R. Tizanidine and ibuprofen in acute low-back pain: Results of a double-blind multicentre study in general practice // J. Intern. Med. Res. 1988.Vol.16. R. 83–91.
10. Bettucci D., Testa L., Calzoni S. et al. Combination of tizanidine and amitriptyline in the prophylaxis of chronic tension — type headache: evaluation of efficacy and impact on quality of life // J Headache Pain. 2006 Vol. 7(1). P. 34–36.
11. Coward D.M. Tizanidine: Neuropharmacology and mechanism of action // Neurol. 1994 Vol. 44 (Suppl. 9). P. 6–11.
12. Gelber D.A., Good D.C., Dromerick A. et al. Open–Label Dose–Titration Safety and Efficacy Study of Tizanidine Hydrochloride in the Treatment of Spasticity Associated With Chronic Stroke // Stroke. 2001. Vol.32. P. 1841–1846.
13. Hutchinson D.R., Daniels F. A multinational study in general practice to evaluate the effectiveness and tolerability of tizanidine in the treatment of painful muscle spasms // Br. J.Clin. Res. 1990 Vol. 1. P. 39–48.
14. Lataste X., Emre M., Davis C., Groves L. Comparative profile of tizanidine in the management of spasticity // Neurol. 1994 Vol. 44 (suppl 9). P.53–59.
15. Leiphart J.W., Dills C.V., Levy R.M. Alpha2 – adrenergic receptor subtype specificity of intrathecally administered tizanidine used for analgesia for neuropathic pain // J. Neurosurg. 2004 Vol. 101(24). P. 641–647.
16. Sirdalud Ternilin Asia–Pacific Study group. Efficacy and gastroprotective effects of tizanidine plus diclofenac versus placebo plus diclofenac in patients with painful muscle spasm // Curr. Ther. Res. 1998 Vol. 59. P. 13–22.
17. Smolenski C., Muff S., Smolenski–Kautz S. A double–blind comparative trial of new muscle relaxant, tizanidine (DS 103–282), and baclofen in the treatment of chronic spasticity in multiple sclerosis // Curr. Med. Res. Opin. 1981 Vol. 7(6). P. 374–383.
18. Tarrico M., Adone R., Pagliacci C., Telaro E. Pharmacological interventions for spasticity following spinal cord injury. Cochrane Database Systematic Review // The Cochrane Library, 2000. Issue 4.
19. van Tulder M., Becker A., ​​Bekkering T. Et al. European guidelines for the management of acute nonspecific low back pain in primary care // Eur. Spine J. 2006. Vol. 15. (Suppl. 2). S.169–S.191.
20. Wallace J.D. Summary of combined clinical analysis of controlled clinical trials with tizanidine // Neurol. 1994 Vol. 44 (suppl 9). P60-P69.

Possibilities of using the drug tizanidine (Sirdalud®) in patients with post-stroke spasticity uMEDp

Post-stroke spasticity significantly limits the patient’s motor abilities, makes it difficult to care for the patient, contributes to the formation of pain syndromes. The article presents a modern view on the pathophysiology of post-stroke spasticity and discusses approaches to treatment. The mechanisms of action and possibilities of the drug tizanidine (Sirdalud®) for the correction of increased muscle tone in stroke patients are considered. The effect of tizanidine is compared with the effect of other muscle relaxants.

Introduction

Spasticity is one of the most common movement disorders in stroke patients. During the first year after a stroke, spasticity is observed in 17–43% of patients [1, 2]. As a rule, spasticity is accompanied by paresis of the corresponding muscles, but there is no strict relationship between these symptoms.

Hemiparesis, a classic clinical example of spastic paresis after a stroke, is characterized by the formation of the Wernicke-Mann position: the shoulder is brought to the body, the forearm is bent, the hand is pronated and flexed, the thigh and lower leg are extended, the foot is in plantar flexion. Due to the “lengthening” of the patient’s leg, when walking, he is forced to bring it through the side, describing a semicircle. These changes occur as a result of an increase in tone, mainly in anti-gravity muscle groups. However, in some cases, other variants of the distribution of increased muscle tone are observed, for example, hyperpronation of the forearm with extension of the fingers, bizarre hand and finger settings, increased tone in the leg flexor muscles, hypersupination of the forearm and hand extensors [3].

Most often, spasticity is detected simultaneously in the upper and lower extremities (68%), however, an isolated appearance of this symptom in the arm (15%) or leg (18%) is also possible [4].

Pathophysiology of spasticity

To date, the pathogenesis of post-stroke spasticity remains open. It is known that this symptom occurs as a result of structural and functional changes in the central nervous system and at the level of the peripheral neuromotor apparatus. So, with spasticity, along with the activation of the cortical zones involved in the organization of movement, and the extrapyramidal pathways of the brain stem, there is a structural and functional reorganization of the segmental structures of the spinal cord. In addition, changes in the neuronal control of the peripheral part of the motor apparatus activate the processes of transformation of the protein composition of soft tissues, primarily skeletal muscles.

In response to a violation of cerebral circulation and the development of a structural and functional defect in the brain, the functional activity of the cortex changes both on the affected and clinically intact sides. In addition, new neuronal connections are being formed, and the zone of representation of the affected body part in the motor and sensory cortex is expanding. In this case, an imbalance arises between intracortical excitation and inhibition towards the predominance of excitation [5–7]. In response to these changes, the extrapyramidal pathways of the brainstem are activated, which begin to generate spontaneous activity that is not associated with the motor activity of the cortex [6].

The main excitatory mediators of the nervous system involved in the regulation of muscle tone are glutamate and aspartate, the main inhibitory neurotransmitter is gamma-aminobutyric acid (GABA). Serotonergic and noradrenergic systems of the brainstem play a certain role in the implementation of muscle tone disorders, which can have both excitatory and inhibitory effects at the level of spinal neuronal networks [8].

A change in the functional interaction between different parts of the central nervous system leads to a reorganization of the segmental apparatus of the spinal cord. New contacts are formed between the neurons of the spinal cord and the descending pathways of the brain, which is accompanied by an increase in reflex excitability at the segmental level and is clinically realized by the formation of “dynamic” spasticity phenomena in the form of clonuses and synkinesis [6].

One of the methods for assessing the functional state of the segmental apparatus of the spinal cord is the study of the parameters of the H-reflex (the response of a muscle to irritation of the sensory fibers of the peripheral nerve). It has been established that with spasticity, the zone of H-reflex evoking expands significantly [9].

Violation of the neuronal control of skeletal muscles leads to the transformation of their protein structure, primarily the myosin phenotype, as well as to changes in the properties of the surrounding soft tissues (tendons and joint capsules). As a result, the proportion of “fast”, but easily fatigued fibers in the muscle increases significantly, and tendon retraction leads to the formation of contractures [8, 10].

Spasticity of different muscle groups affects the patient’s motor activity differently. For example, spasticity of the quadriceps femoris muscle under conditions of paresis can help maintain an upright posture by maintaining the supporting function of the leg. At the same time, spasticity of the muscles of the hand always limits its functionality. In general, post-stroke spasticity negatively affects motor activity and is usually accompanied by a number of dynamic motor phenomena: involuntary movements, clonuses or spasms, spastic synkinesis. In addition to the deterioration of motor functions, post-stroke spasticity can contribute to the development of post-stroke pain syndrome in the shoulder area, the prevalence of which varies from 16% in the early recovery period to 36% in the late recovery period [11].

The severity of clinical symptoms in post-stroke spasticity and its impact on quality of life are assessed by the doctor, the patient, as well as those caring for the patient. First of all, the degree of spasticity at rest is determined, for which the Ashworth scale is used, then the functional state of the limb during movements is assessed, as well as the presence of symptoms accompanying spasticity (pain, discomfort, pathological synkinesis). Taking into account all these factors, a plan of therapeutic measures is developed.

Treatment

Patients with post-stroke spasticity are indicated for both non-drug and drug treatment.

Non-pharmacological treatment includes physical exercises, positional treatment, use of orthoses, massage, thermotherapy, cryotherapy, electromyostimulation, biofeedback methods [3, 12]. Since these activities, as a rule, have a short-term effect, they should be carried out continuously, not limited to one or two courses per year. In this regard, it is necessary to train patients and their caregivers in techniques that can be used at home.

Local injections of botulinum toxin preparations, which consist of neurotoxin type A and some other proteins, are considered to be the optimal medical method for correcting local spasticity. Botulinum toxin blocks the release of acetylcholine into the synaptic cleft. The most significant results of botulinum toxin therapy include improved walking and increased self-care opportunities. The effect develops after four to seven days and persists in most cases for 12–16 weeks [13]. However, the maximum effectiveness of the drug is achieved when it is administered under the control of electromyography, which is not always available. In addition, injections of the drug are not recommended for patients taking therapeutic doses of anticoagulants [13]. In general, despite the development of care for stroke patients, today the possibilities of botulinum toxin therapy are limited.

Another method of local action is the use of alcoholic and phenol neurolysis of the motor branches of the nerves, which leads to their irreversible destruction and fibrosis of the surrounding tissues. The procedure is carried out under the control of electromyography and/or ultrasound [13]. The disadvantage of this method is the side effects in the form of dysesthesia, weakness and local swelling at the injection site [1]. Currently, neurolysis is rarely used (mainly in bedridden patients), as a rule, in combination with botulinum therapy. The effect lasts from two to 36 months [13].

Of the first-line oral medications used for post-stroke spasticity, international guidelines indicate centrally acting muscle relaxants: tizanidine and baclofen. It is also possible to use tolperisone, diazepam, gabapentin [13]. In the treatment of cerebral spasticity, tizanidine is most often used, while in spinal spasticity, tizanidine and baclofen are used [14].

Tizanidin in the treatment of post-stroke spasticity

Tizanidine (Sirdalud®) is a central agonist of imidazoline and alpha-2-adrenergic receptors both at the spinal and supraspinal levels [13, 15]. Tizanidine enhances presynaptic inhibition of motor neurons by reducing the release of excitatory amino acids (aspartate and glutamate) from spinal interneurons, as well as by inhibiting the activity of facilitating cerebrospinal pathways. In addition, tizanidine prevents the release of substance P by thin sensory fibers, reduces the functional activity of the locus coeruleus in the brainstem and reduces the excitability of the segmental apparatus of the spinal cord [16].

Controlled clinical studies have shown the efficacy of tizanidine in post-stroke spasticity. Thus, one study showed that tizanidine at a dose of 8 mg/day reduces the level of facilitation of the H-reflex in all patients (n = 14) with post-stroke spasticity. This does not happen with placebo. Decreased facilitation was observed on both the affected and clinically intact side. At the same time, when taking tizanidine, there is no change in the indicator H _max /M _max and the threshold of H-reflex evoking, which probably indicates the absence of the effect of the drug on the excitability of spinal motor neurons. There was a significant decrease in the degree of spasticity from 2.9 to 1.9 points on the Ashworth scale [17].

Several studies have shown a dose-dependent antispastic effect of tizanidine. In the group of patients with multiple sclerosis (n = 17) and the degree of spasticity in the lower extremities of two or three points on the Ashworth scale, a relationship was shown between the concentration of the drug in the blood and its antispastic effect. At the same time, there was no relationship between certain concentrations of the drug and the antispastic effect in the examined group, which indicates the need for individual dose selection. It was noted that the effect of 2 mg tizanidine did not differ from that of placebo. Thus, the degree of spasticity two hours after taking 2 mg of the drug decreased by 29% (when taking placebo – by 28%), when taking 8 mg of tizanidine – by 38%. The antispastic effect was not accompanied by a decrease in muscle strength. In this study, the data of a clinical assessment of the degree of spasticity were confirmed by the results of a quantitative study of muscle tone using an electrogoniometer (the device showed a high degree of sensitivity and reliability) [8].

The dose-dependence of the antispastic effect of tizanidine in patients with post-stroke spasticity was studied in a multicenter study that included 47 patients, the degree of spasticity was two to three points on the Ashworth scale, the time after stroke was six months [16]. The dose of the drug was titrated to 36 mg (reaching the maximum dosage in 21% of patients). As a result of taking tizanidine for 16 weeks, the degree of spasticity decreased without changing muscle strength, the intensity of the pain syndrome and, as a result, the quality of life of patients improved [16].

Thus, studies have confirmed the dose-dependent clinical effect of the drug, the treatment of spasticity requires the use of higher doses of tizanidine than the treatment of pain syndromes. The lack of effect in some cases may be due to an insufficient dose of the drug [8, 18].

Analysis of the results of several studies investigating the anti-spastic effect of tizanidine in comparison with placebo and other oral muscle relaxants showed a decrease in the degree of spasticity when taking tizanidine by 21-37%, while for placebo this indicator ranged from 4 to 9%. At the same time, muscle tone decreased in 60–80% of patients in the tizanidine group, in 60–65% in the baclofen group, and in 60–83% in the diazepam group. The tolerability of the drug was assessed as very good in 44-100% of patients in the tizanidine group, 38-90% in the baclofen group and 20-54% in the diazepam group. At the same time, in the tizanidine group, patients did not feel an increase in muscle weakness, in contrast to patients taking baclofen. All drugs caused drowsiness [19]. Based on the combination of efficacy and tolerability indicators, tizanidine demonstrated significant advantages in the treatment of post-stroke spasticity compared to other oral muscle relaxants [16, 19, 20].

Studies comparing the treatment of tizanidin and botulinum toxin for post-stroke spasticity in the upper extremity have shown that both drugs are effective. At the same time, in order to achieve optimal results, it is necessary to strictly observe the dosages and determine the injection sites of botulinum toxin [18]. Another study examined the combined use of botulinum toxin with oral antispastic drugs in a group of children with cerebral palsy. It has been established that the combination of botulinum toxin with tizanidine is more effective than the combination of botulinum toxin and baclofen [21].

Orally administered tizanidine is rapidly absorbed, with peak plasma concentrations reached after one to two hours. The optimal therapeutic effect, as a rule, develops when the drug is prescribed in a daily dose of 12-24 mg, divided into three doses; the range of effective doses is 2–36 mg [22]. The maximum daily dose is 36 mg. Increasing and decreasing the dosage should be carried out gradually. Tizanidine is metabolized in the liver mainly by the CYP1A2 isoenzyme. It should be remembered: drugs such as ciprofloxacin and fluvoxamine inhibit this enzyme, as a result of which the hypotensive effect of tizanidine can be significantly increased. Particular caution should be exercised when combining the drug with antihypertensive agents. Abrupt discontinuation of tizanidine may lead to the development of a withdrawal syndrome, especially with long-term treatment in conjunction with antihypertensive drugs.

The most common side effects associated with taking tizanidine are drowsiness, dizziness, and lowering blood pressure. It is also possible the appearance of general weakness, dry mouth, sleep disturbance, hallucinations [8, 17]. It should be noted that all side effects are dose-dependent and can be minimized with proper dose titration. When they appear, the dosage should be reduced to the previous level for several days, after which the increase in dose should be resumed [8]. As a rule, with poor tolerance, side effects appear even at minimal dosages of the drug [8, 22].

Tizanidine is also currently available in a dosage of 6 mg in the form of modified release capsules (Sirdalud® MP). For most patients, the optimal dose is 12 mg/day, in rare cases, 24 mg/day [22]. Treatment begins with one capsule per day, if necessary, the dose is increased every seven days. It should be noted that Sirdalud® MR showed high efficiency in relation to central sensitization in the development of post-stroke pain syndrome in the shoulder area [11].

Other muscle relaxants

Another first-line drug for the treatment of post-stroke spasticity is baclofen, an agonist of the GABA B-type receptors located in the primary sensory afferent endings of the spinal cord. By enhancing the polarization of interneuron membranes, baclofen prevents the flow of calcium into presynaptic terminals and the release of endogenous transmitters, thereby inhibiting mono- and polysynaptic reflexes of the spinal cord [13].

The maximum dosage is 120 mg/day, dose changes up or down should be done once a week and not more than 15 mg. Side effects of baclofen are also dose-dependent: most often there are general weakness, drowsiness. Experimental animal studies have shown that GABAergic drugs can reduce brain plasticity in the early recovery period after a stroke, and therefore it is undesirable to prescribe them at this time. The drug is also not recommended for elderly patients due to the development of severe drowsiness [13].

Attention should be paid to the possibility of intrathecal administration of baclofen using a pump. It is a highly effective treatment for severe spasticity, including stroke patients, and significantly reduces the incidence of side effects. However, this method is used relatively rarely, due to the high cost of equipment [13].

Tolperisone, a centrally acting muscle relaxant, similar in structure to lidocaine, is widely used in our country. The drug stabilizes the membranes of nerve cells. The use of tolperisone has shown high efficacy and safety in reducing muscle tone in spasticity in several controlled studies [23, 24].

In Russia, a comparative study of the effectiveness of various muscle relaxants in patients with post-stroke spasticity was carried out, the results of which showed a decrease in the degree of spasticity and improvement in household adaptation in patients taking tolperisone and tizanidine. At the same time, tolperisone was administered at a dose of up to 900 mg/day. During the study, no significant side effects were found when taking tolperisone [23]. However, large international studies have not been conducted on this drug for post-stroke spasticity. It is advisable to start treatment with tolperison with a daily dose of 300 mg, which, if necessary, can be increased to 900 mg.

Other oral drugs used to reduce muscle tone in spasticity are benzodiazepines, gabapentin and dantrolene (not registered in Russia). However, data on their effectiveness in post-stroke spasticity have not been obtained [13].

The literature discusses the possibility of combining different muscle relaxants in order to achieve the maximum effect. To date, there is no evidence base for recommending any combination of drugs, while the likelihood of side effects summation increases, and therefore attempts to combine oral muscle relaxants seem irrational [13].

Conclusion

Regardless of the severity of post-stroke spasticity, it should be remembered that spasticity increases significantly in the presence of pain syndromes, bedsores, constipation, urinary tract infections.