What are the FDA-approved and off-label uses of tizanidine 2mg. How does tizanidine work to manage spasticity. What clinical studies support the efficacy of tizanidine compared to other muscle relaxants. How can tizanidine benefit patients with various neurological conditions.

Understanding Tizanidine: A Versatile Muscle Relaxant

Tizanidine is a centrally acting alpha-2 receptor agonist widely used as an anti-spastic agent for various medical conditions. This medication plays a crucial role in managing spasticity and muscle tension associated with neurological disorders. Understanding its uses, mechanism of action, and clinical applications is essential for healthcare providers and patients alike.

FDA-Approved Indications for Tizanidine

The U.S. Food and Drug Administration (FDA) has approved tizanidine for specific indications related to spasticity management. These include:

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

In these conditions, tizanidine helps reduce muscle stiffness and spasms, improving patient comfort and functionality. Are there other uses for tizanidine beyond these FDA-approved indications. Indeed, healthcare providers often prescribe tizanidine for off-label uses based on clinical experience and research findings.

Exploring Off-Label Uses of Tizanidine

While not officially approved by the FDA for these purposes, tizanidine has shown efficacy in managing various other conditions:

1. Chronic neck and lower back pain
2. Rebound headaches due to analgesic withdrawal
3. Chronic migraine headaches
4. Refractory insomnia in spastic quadriplegic patients
5. Regional musculoskeletal pain syndromes

These off-label uses highlight the versatility of tizanidine in addressing a range of musculoskeletal and neurological issues. How does tizanidine compare to other muscle relaxants in terms of efficacy and side effects. Clinical studies provide valuable insights into this question.

Clinical Studies: Tizanidine vs. Other Muscle Relaxants

Numerous studies have compared tizanidine to other commonly prescribed muscle relaxants, such as baclofen and diazepam. Key findings from these studies include:

• Efficacy: Tizanidine showed similar effectiveness in reducing spasticity compared to baclofen and diazepam in patients with multiple sclerosis or cerebrovascular lesions.
• Muscle strength: Patients treated with tizanidine experienced significant improvement in muscle strength, often surpassing the improvements seen with other medications.
• Adverse effects: Tizanidine generally demonstrated a more favorable side effect profile compared to controlled substances like diazepam.
• Tolerance: Studies suggest that patients tolerate tizanidine slightly better than diazepam and baclofen.

These findings underscore the potential benefits of tizanidine in managing spasticity and related symptoms. How does tizanidine achieve these effects at the physiological level. Understanding its mechanism of action provides crucial insights into its therapeutic potential.

Mechanism of Action: How Tizanidine Works

Tizanidine’s effectiveness in managing spasticity and muscle tension stems from its unique mechanism of action. As an imidazoline derivative and centrally acting alpha-2 receptor agonist, tizanidine influences the central nervous system in several ways:

1. Inhibition of excitatory amino acids: Tizanidine reduces the release of glutamate and aspartate from spinal interneurons.
2. Enhanced presynaptic inhibition: By acting on motor neurons, tizanidine decreases their excitability.
3. Modulation of spinal polysynaptic pathways: This action contributes to the overall reduction in muscle tone and spasticity.
4. Alpha-2 receptor-mediated effects: Tizanidine’s interaction with these receptors underlies its additional anti-nociceptive and anti-convulsant properties.

The cumulative effect of these actions is a reduction in the facilitation of spinal motor neurons, leading to decreased muscle tension and spasticity. Does tizanidine have any effects beyond its primary mechanism of action. Indeed, research suggests additional benefits in pain management and other neurological conditions.

Tizanidine in Pain Management and Neuropathic Conditions

Beyond its primary use in spasticity management, tizanidine has shown promise in addressing various pain-related conditions:

• Neuropathic pain: Animal studies suggest potential benefits in managing conditions like trigeminal neuralgia.
• Perioperative pain management: Tizanidine may offer advantages similar to clonidine in surgical settings.
• Chronic pain syndromes: Its efficacy in chronic neck and lower back pain highlights its potential in managing persistent pain conditions.
• Migraine management: Off-label use for chronic migraine headaches suggests potential benefits in this area.

These applications expand the therapeutic potential of tizanidine beyond its primary indications. How does tizanidine fit into broader treatment strategies for neurological conditions. Guidelines from professional organizations provide valuable insights.

Guidelines and Recommendations for Tizanidine Use

The American Academy of Neurology has provided guidelines on the use of tizanidine in various neurological conditions:

• Generalized spasticity in cerebral palsy: Tizanidine is recommended as a treatment option.
• Segmental/localized spasticity: Botulinum toxin-A is considered more effective than tizanidine for targeted treatment.

These guidelines help healthcare providers make informed decisions about when and how to use tizanidine in their treatment plans. Are there any emerging applications for tizanidine in medical practice. Recent research points to potential new uses for this versatile medication.

Emerging Applications: Tizanidine in Opioid Withdrawal

A recent study has highlighted a novel application for tizanidine and other alpha-2 agonists: medically supervised opioid withdrawal. This finding opens up new possibilities for using tizanidine in addiction medicine and pain management. Key points from this research include:

• Potential role in detoxification therapy
• Assistance in managing withdrawal symptoms
• Possible reduction in opioid dependence

This emerging application underscores the ongoing research into tizanidine’s diverse therapeutic potential. How does tizanidine compare to other medications used in opioid withdrawal management. Further studies are needed to fully elucidate its efficacy and safety profile in this context.

Tizanidine in Combination Therapies

While tizanidine is often used as a standalone treatment, its effectiveness can sometimes be enhanced when combined with other therapies. Some combination approaches include:

1. Tizanidine with physical therapy: This combination can help improve muscle function and reduce spasticity more effectively than medication alone.
2. Tizanidine and botulinum toxin: For localized spasticity, combining these treatments may provide more comprehensive relief.
3. Tizanidine with other pain medications: In chronic pain management, tizanidine may be used alongside other analgesics for enhanced pain control.

These combination therapies highlight the versatility of tizanidine in multi-modal treatment approaches. How should healthcare providers determine the optimal dosage and duration of tizanidine treatment. Individualized assessment and careful monitoring are key to maximizing benefits while minimizing potential side effects.

Dosage Considerations and Administration

Proper dosing of tizanidine is crucial for achieving optimal therapeutic effects while minimizing adverse reactions. Key considerations include:

• Starting dose: Typically 2mg to 4mg, taken up to three times daily
• Dose titration: Gradual increase based on patient response and tolerability
• Maximum daily dose: Generally not to exceed 36mg per day
• Administration timing: Often taken at bedtime to minimize daytime sedation

Healthcare providers should tailor the dosage to each patient’s specific needs and medical condition. Are there any special considerations for certain patient populations. Indeed, dosage adjustments may be necessary for elderly patients or those with liver or kidney impairment.

Patient Monitoring and Follow-up

Regular monitoring is essential for patients taking tizanidine to ensure optimal therapeutic outcomes and detect any potential adverse effects. Key aspects of patient monitoring include:

1. Assessment of spasticity reduction and functional improvement
2. Evaluation of side effects, particularly sedation and dizziness
3. Liver function tests, especially in patients on long-term therapy
4. Blood pressure monitoring, as tizanidine can cause hypotension
5. Regular follow-up appointments to adjust dosage as needed

Proper monitoring allows healthcare providers to optimize tizanidine therapy and ensure patient safety. How can patients contribute to the success of their treatment. Patient education and adherence to prescribed regimens are crucial factors in achieving optimal outcomes.

Patient Education and Self-Management

Empowering patients with knowledge about tizanidine can improve treatment outcomes and safety. Key points for patient education include:

• Proper dosing schedule and administration instructions
• Potential side effects and when to seek medical attention
• Importance of avoiding alcohol and certain medications while taking tizanidine
• Strategies for managing sedation, such as timing doses around daily activities
• The need for regular follow-up appointments and monitoring

By providing comprehensive education, healthcare providers can help patients make informed decisions about their treatment and actively participate in their care. Can lifestyle modifications complement tizanidine therapy. Indeed, certain lifestyle changes can enhance the effectiveness of tizanidine and improve overall management of spasticity and related symptoms.

Lifestyle Modifications to Complement Tizanidine Therapy

While tizanidine can significantly improve spasticity and muscle tension, combining medication with lifestyle modifications can lead to even better outcomes. Patients may benefit from:

1. Regular stretching exercises to maintain muscle flexibility
2. Physical therapy to improve strength and range of motion
3. Stress reduction techniques, such as meditation or yoga, to help manage muscle tension
4. Proper sleep hygiene to enhance the effects of tizanidine and reduce fatigue
5. Dietary adjustments to support overall health and potentially reduce inflammation

These lifestyle modifications can work synergistically with tizanidine to improve patient quality of life and functional outcomes. How do healthcare providers determine when to adjust or discontinue tizanidine therapy. Regular assessment of treatment efficacy and patient needs is crucial for optimizing long-term management.

Long-term Management and Treatment Adjustments

The management of conditions requiring tizanidine often involves long-term care and periodic treatment adjustments. Key considerations for long-term management include:

• Regular reassessment of spasticity and related symptoms
• Evaluation of treatment goals and patient satisfaction
• Consideration of alternative or additional therapies as needed
• Monitoring for potential long-term side effects or complications
• Gradual tapering of medication if discontinuation is warranted

By taking a proactive approach to long-term management, healthcare providers can ensure that patients continue to receive optimal benefits from tizanidine therapy while minimizing potential risks. Can tizanidine be safely used in combination with other medications. Understanding potential drug interactions is crucial for safe and effective treatment.

Drug Interactions and Precautions

While tizanidine is generally well-tolerated, it can interact with various medications and substances. Healthcare providers should be aware of potential interactions, including:

1. CYP1A2 inhibitors: Medications like fluvoxamine can significantly increase tizanidine levels
2. Alcohol: Can enhance the sedative effects of tizanidine
3. Other CNS depressants: Combining tizanidine with drugs like benzodiazepines may increase sedation
4. Antihypertensive medications: May potentiate the blood pressure-lowering effects of tizanidine
5. Oral contraceptives: Can affect tizanidine metabolism and potentially alter its effectiveness

Careful consideration of these interactions is essential for safe prescribing and optimal patient outcomes. How does tizanidine compare to newer medications in the management of spasticity and related conditions. Ongoing research continues to explore the relative benefits and drawbacks of various treatment options.

Future Directions in Spasticity Management

As research in neurology and pharmacology progresses, new approaches to managing spasticity and related conditions are emerging. Some areas of ongoing investigation include:

• Development of novel alpha-2 agonists with improved side effect profiles
• Exploration of combination therapies to enhance efficacy and reduce side effects
• Investigation of targeted drug delivery systems for localized spasticity treatment
• Research into the potential neuroprotective effects of alpha-2 agonists
• Studies on the long-term outcomes and quality of life improvements with various treatment approaches

These ongoing research efforts hold promise for improving the management of spasticity and related neurological conditions in the future. How can healthcare providers stay informed about the latest developments in this field. Continuing education and engagement with professional organizations are key to staying up-to-date with evolving treatment paradigms.

Interprofessional Collaboration in Tizanidine Therapy

Effective management of patients using tizanidine often requires a collaborative approach involving multiple healthcare professionals. Key aspects of interprofessional collaboration include:

1. Communication between prescribing physicians and pharmacists to ensure appropriate dosing and monitor for potential drug interactions
2. Coordination with physical therapists to optimize the benefits of tizanidine in conjunction with rehabilitation programs
3. Collaboration with occupational therapists to assess and improve functional outcomes
4. Engagement with nursing staff for patient education and monitoring of side effects
5. Consultation with pain management specialists for patients using tizanidine for chronic pain conditions

By fostering a collaborative approach, healthcare teams can provide comprehensive care that addresses all aspects of a patient’s condition and treatment. How can healthcare systems support this interprofessional approach to tizanidine therapy. Implementing integrated care models and utilizing electronic health records can facilitate seamless communication and coordination among healthcare providers.

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]

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• Comment on this article.

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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.