Zanaflex 4mg Tablets
It is used to relax muscles.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Skeletal Muscle Relaxant
Pharmacologic Class
Alpha-2 Adrenergic Agonist
Pregnancy Category
C
FDA Approved
Dec 1996
DEA Schedule
Not Controlled
Overview
What is this medicine?
Tizanidine is a muscle relaxant used to treat muscle spasms and stiffness (spasticity) caused by conditions like multiple sclerosis or spinal cord injury. It works by calming overactive nerves in the brain and spinal cord that control muscle movement.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication with or without food, but be consistent in how you take it each time. If you take it with food, always take it with food. If you take it on an empty stomach, always take it on an empty stomach.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about disposing of your medication, consult your pharmacist. You may also want to check if there are drug take-back programs in your area.
Missing a Dose
If you take this medication regularly and miss a dose, take it as soon as you remember. However, if it's close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses. If you take this medication as needed, do not take it more frequently than directed by your doctor.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication with or without food, but be consistent in how you take it each time. If you take it with food, always take it with food. If you take it on an empty stomach, always take it on an empty stomach.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about disposing of your medication, consult your pharmacist. You may also want to check if there are drug take-back programs in your area.
Missing a Dose
If you take this medication regularly and miss a dose, take it as soon as you remember. However, if it's close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses. If you take this medication as needed, do not take it more frequently than directed by your doctor.
Lifestyle & Tips
- Avoid alcohol consumption while taking tizanidine, as it can increase drowsiness and dizziness.
- Avoid activities requiring mental alertness, such as driving or operating machinery, until you know how tizanidine affects you.
- Do not stop taking tizanidine abruptly, as this can lead to serious withdrawal symptoms like rebound high blood pressure, fast heart rate, and increased muscle spasms. Your doctor will guide you on how to slowly reduce the dose.
- Take tizanidine consistently with or without food, but try to be consistent. If you take it with food, always take it with food. If you take it without food, always take it without food, as food can affect how much medicine your body absorbs.
- Rise slowly from a sitting or lying position to avoid dizziness or fainting due to low blood pressure.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial 2 mg once daily, titrated up to effect
Dose Range:
2 - 36 mg
Condition-Specific Dosing:
spasticity:
Initial 2 mg, increased by 2-4 mg at 1-4 day intervals based on response and tolerability. Max single dose 16 mg. Max daily dose 36 mg in 3 divided doses.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
CrCl < 25 mL/min: Reduce initial dose (e.g., 2 mg once daily), titrate slowly based on response and tolerability.
Moderate:
CrCl < 25 mL/min: Reduce initial dose (e.g., 2 mg once daily), titrate slowly based on response and tolerability.
Severe:
CrCl < 25 mL/min: Reduce initial dose (e.g., 2 mg once daily), titrate slowly based on response and tolerability.
Dialysis:
Not well studied; significant dose reduction and careful monitoring are likely required. Tizanidine is not significantly removed by hemodialysis.
Hepatic Impairment:
Mild:
Use with caution; monitor liver function tests (LFTs).
Moderate:
Use with caution; monitor liver function tests (LFTs).
Severe:
Not recommended due to extensive hepatic metabolism and potential for increased systemic exposure.
Pharmacology
Mechanism of Action
Tizanidine is an alpha-2 adrenergic agonist. It reduces spasticity by increasing presynaptic inhibition of motor neurons at the alpha-2 adrenergic receptor sites within the spinal cord. This action is thought to reduce the release of excitatory amino acids, thereby inhibiting polysynaptic reflexes involved in muscle tone.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 40% (tablets)
Tmax:
1-2 hours
FoodEffect:
For tablets, food increases Tmax by approximately 1 hour and Cmax by approximately 30%, but AUC is not significantly affected. Zanaflex tablets and capsules are NOT bioequivalent and should not be interchanged without retitration.
Distribution:
Vd:
2.4 L/kg
ProteinBinding:
Approximately 30%
CnssPenetration:
Yes
Elimination:
HalfLife:
Approximately 2.5 hours (parent drug)
Clearance:
High systemic clearance
ExcretionRoute:
Renal (approximately 60% as metabolites, 5% unchanged drug)
Unchanged:
Approximately 5%
Pharmacodynamics
OnsetOfAction:
1-2 hours
PeakEffect:
1-2 hours
DurationOfAction:
3-6 hours
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems: dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes
Signs of a urinary tract infection (UTI): blood in the urine, burning or pain when passing urine, frequent or urgent need to urinate, fever, lower stomach pain, or pelvic pain
Severe dizziness or fainting
Confusion
Hallucinations (seeing or hearing things that are not there)
Mood changes or changes in behavior
Slow heartbeat
Fever, chills, or sore throat
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only minor ones. If you notice any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Dry mouth
* Dizziness, drowsiness, tiredness, or weakness
This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch. Your doctor can provide medical advice about side effects.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems: dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes
Signs of a urinary tract infection (UTI): blood in the urine, burning or pain when passing urine, frequent or urgent need to urinate, fever, lower stomach pain, or pelvic pain
Severe dizziness or fainting
Confusion
Hallucinations (seeing or hearing things that are not there)
Mood changes or changes in behavior
Slow heartbeat
Fever, chills, or sore throat
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only minor ones. If you notice any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Dry mouth
* Dizziness, drowsiness, tiredness, or weakness
This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch. Your doctor can provide medical advice about side effects.
Seek Immediate Medical Attention If You Experience:
- Severe dizziness or lightheadedness, especially when standing up.
- Fainting spells.
- Yellowing of the skin or eyes (jaundice), dark urine, persistent nausea/vomiting, or severe stomach pain (signs of liver problems).
- Severe weakness or extreme tiredness.
- Confusion or hallucinations.
- Any signs of an allergic reaction (rash, itching, swelling, severe dizziness, trouble breathing).
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are currently taking ciprofloxacin or fluvoxamine, as these medications may interact with this drug.
Please note that this is not an exhaustive list of all potential interactions. To ensure your safety, it is crucial to disclose all of your medications, including:
Prescription and over-the-counter (OTC) drugs
Natural products
* Vitamins
Additionally, inform your doctor about any existing health problems. This information will help your doctor determine whether it is safe for you to take this medication in conjunction with your other medications and health conditions.
Remember, do not start, stop, or change the dosage of any medication without first consulting your doctor. This precaution is essential to avoid potential interactions and ensure your safety while taking this medication.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are currently taking ciprofloxacin or fluvoxamine, as these medications may interact with this drug.
Please note that this is not an exhaustive list of all potential interactions. To ensure your safety, it is crucial to disclose all of your medications, including:
Prescription and over-the-counter (OTC) drugs
Natural products
* Vitamins
Additionally, inform your doctor about any existing health problems. This information will help your doctor determine whether it is safe for you to take this medication in conjunction with your other medications and health conditions.
Remember, do not start, stop, or change the dosage of any medication without first consulting your doctor. This precaution is essential to avoid potential interactions and ensure your safety while taking this medication.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
To ensure your safety, avoid driving and other activities that require alertness until you understand how this medication affects you. When getting up from a sitting or lying down position, rise slowly to minimize the risk of dizziness or fainting. Be cautious when climbing stairs.
Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter medications that may impair your reactions, consult with your doctor.
If you have been taking a high dose of this medication or using it regularly, do not stop taking it abruptly without first discussing it with your doctor. Stopping the medication suddenly may increase your risk of side effects. If you need to discontinue use, your doctor will guide you on how to gradually stop taking it.
As directed by your doctor, have your blood tested regularly and discuss the results with them.
Do not switch between the capsule and tablet forms of this medication without consulting your doctor. If your doctor changes your medication from one form to another (e.g., from capsules to tablets), the new form may interact differently with food. Your doctor may monitor you closely after switching to the new form to check for any differences in how it works or potential side effects.
Animal studies have shown that this medication can cause fertility problems. Although it is unclear if this medication affects human fertility, discuss any concerns with your doctor.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are pregnant, plan to become pregnant, or are breastfeeding, inform your doctor. You and your doctor will need to discuss the potential benefits and risks of this medication to you and your baby.
To ensure your safety, avoid driving and other activities that require alertness until you understand how this medication affects you. When getting up from a sitting or lying down position, rise slowly to minimize the risk of dizziness or fainting. Be cautious when climbing stairs.
Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter medications that may impair your reactions, consult with your doctor.
If you have been taking a high dose of this medication or using it regularly, do not stop taking it abruptly without first discussing it with your doctor. Stopping the medication suddenly may increase your risk of side effects. If you need to discontinue use, your doctor will guide you on how to gradually stop taking it.
As directed by your doctor, have your blood tested regularly and discuss the results with them.
Do not switch between the capsule and tablet forms of this medication without consulting your doctor. If your doctor changes your medication from one form to another (e.g., from capsules to tablets), the new form may interact differently with food. Your doctor may monitor you closely after switching to the new form to check for any differences in how it works or potential side effects.
Animal studies have shown that this medication can cause fertility problems. Although it is unclear if this medication affects human fertility, discuss any concerns with your doctor.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are pregnant, plan to become pregnant, or are breastfeeding, inform your doctor. You and your doctor will need to discuss the potential benefits and risks of this medication to you and your baby.
Overdose Information
Overdose Symptoms:
- Somnolence (extreme drowsiness)
- Bradycardia (slow heart rate)
- Hypotension (low blood pressure)
- Dizziness
- Respiratory depression (slow, shallow breathing)
- Coma
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Management is primarily supportive, including maintaining airway, breathing, and circulation. Activated charcoal may be considered if ingested recently.
Drug Interactions
Contraindicated Interactions
- Strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) due to significant increase in tizanidine exposure and risk of adverse effects (hypotension, somnolence).
Major Interactions
- Other CYP1A2 inhibitors (e.g., amiodarone, mexiletine, propafenone, verapamil, oral contraceptives, zileuton, ticlopidine) - may increase tizanidine levels, requiring dose reduction and careful monitoring.
- Alcohol - increased risk of sedation and hypotension.
- Other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, antihistamines) - additive CNS depression (sedation, somnolence, hypotension).
Moderate Interactions
- Antihypertensives - additive hypotensive effects, monitor blood pressure.
- Other alpha-2 adrenergic agonists (e.g., clonidine) - additive hypotensive and sedative effects.
- QT-prolonging drugs - theoretical risk of additive QT prolongation, though tizanidine itself is not a significant QT prolonger.
Minor Interactions
- Not many specific minor interactions beyond general caution with drugs that may cause dizziness or drowsiness.
Monitoring
Baseline Monitoring
Liver Function Tests (LFTs)
Rationale: To establish baseline and identify pre-existing hepatic impairment, as tizanidine is extensively metabolized by the liver and can cause liver injury.
Timing: Prior to initiation of therapy.
Blood Pressure
Rationale: To establish baseline and monitor for hypotensive effects, especially orthostatic hypotension.
Timing: Prior to initiation of therapy.
Routine Monitoring
Liver Function Tests (LFTs)
Frequency: At 1, 3, and 6 months after initiating therapy or increasing dose, then periodically as clinically indicated. More frequently if symptoms of liver injury develop.
Target: Within normal limits or stable from baseline.
Action Threshold: Discontinue if ALT or AST are persistently >3 times the upper limit of normal (ULN) or if accompanied by clinical symptoms of liver injury.
Blood Pressure (sitting and standing)
Frequency: Periodically, especially during dose titration and if symptoms of hypotension occur.
Target: Maintain within patient's normal range, avoid symptomatic hypotension.
Action Threshold: Significant or symptomatic hypotension (e.g., dizziness, syncope) requires dose reduction or discontinuation.
Assessment of Spasticity and Adverse Effects
Frequency: Regularly during dose titration and maintenance.
Target: Improved spasticity with tolerable side effects.
Action Threshold: Lack of efficacy or intolerable side effects (e.g., severe sedation, dry mouth, asthenia) require dose adjustment or discontinuation.
Symptom Monitoring
- Dizziness
- Somnolence
- Dry mouth
- Asthenia (weakness)
- Hypotension (lightheadedness, fainting)
- Bradycardia
- Symptoms of liver injury (e.g., nausea, vomiting, dark urine, jaundice, abdominal pain)
- Rebound hypertension or hypertonia upon abrupt discontinuation
Special Patient Groups
Pregnancy
Tizanidine is Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm based on animal studies (skeletal abnormalities, increased fetal mortality) at doses higher than human therapeutic doses.
Second Trimester:
Potential for fetal harm based on animal studies.
Third Trimester:
Potential for fetal harm based on animal studies. Risk of withdrawal symptoms in neonate if used close to delivery is unknown but possible with CNS depressants.
Lactation
Tizanidine is excreted in the milk of lactating rats. It is not known whether tizanidine is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
L3 (Moderately Safe - limited human data, potential for adverse effects). Monitor infant for sedation, poor feeding, and hypotonia.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Use is generally not recommended.
Geriatric Use
Geriatric patients may be more sensitive to the hypotensive and sedative effects of tizanidine. Start with lower doses and titrate slowly, monitoring closely for adverse effects.
Clinical Information
Clinical Pearls
- Tizanidine tablets and capsules are NOT bioequivalent and should not be interchanged without retitration of the dose.
- Abrupt discontinuation of tizanidine, especially after prolonged use or high doses, can lead to rebound hypertension, tachycardia, and hypertonia. Taper the dose slowly over several days to weeks.
- Significant first-pass metabolism contributes to its relatively low oral bioavailability.
- Patients should be warned about the potential for hypotension (especially orthostatic) and sedation, particularly during initial dosing and dose increases.
- Liver function tests should be monitored due to the risk of hepatotoxicity, though rare.
Alternative Therapies
- Baclofen (oral, intrathecal)
- Dantrolene
- Diazepam (for acute spasms)
- Gabapentin (off-label for spasticity)
- Botulinum toxin injections (for focal spasticity)
- Physical therapy
- Occupational therapy
Cost & Coverage
Average Cost:
Varies widely, typically $10-$50 per 30 tablets (generic 4mg)
Generic Available:
Yes
Insurance Coverage:
Tier 1 or Tier 2 (for generic formulations)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further evaluation and guidance. To ensure your safety and the effectiveness of your treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it is a good idea to consult with your pharmacist for more information. If you have any questions or concerns about your medication, do not hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened, as this information is crucial for proper treatment.