Article

Tizanidine (Zanaflex, Comfort Pac-Tizanidine): Uses, Dosage, Side Effects, and Abuses
January 30, 20190743

 

 What is Tizanidine?

Tizanidine hydrochloride (or Tizanidine HCL) is a prescription drug sold under the brand name Zanaflex®, Comfort Pac-Tizanidine, and several generic names. It belongs to a class of drugs called muscle relaxants used to relieve muscle spasms.1-3

Tizanidine hydrochloride is available in the following forms4:

  • Tizanidine capsules: 2 mg, 4 mg or 6 mg
  • Tizanidine tablets: 4 mg

 

How does Tizanidine work?

Tizanidine works by increasing the activation of a group of receptors found on the surface of your nerves called α2-adrenergic receptors.1

α2-adrenergic regulate how often your nerves fire.17

When your nerves fire they release chemicals into a small space between themselves and the next nerve, called a “synapse”. These chemicals travel across the synapse and activate the next nerve.17

Some of these chemicals, however, do not make it all the way across the synapse. Instead, they get caught by the α2-adrenergic receptors on the surface of the nerve that they were released from. Binding of these chemicals to its α2-adrenergic receptors tells a nerve that it has already “fired” and should stop releasing chemicals.17

Tizanidine activates the α2-adrenergic receptors on your nerves, causing them to think that they have already “fired” and keeping them from firing again.17

This decreases the nerve signals from your brain to your muscles telling them to contract. With fewer nerve signals from your brain, your muscles can relax. This helps relieve painful muscle stiffness, spasms or spasticity (a combination of stiffness and spasms).1,17

Figure 1: Tizanidine Mechanism of Action.

Chemicals (red circles) are released into the space between nerves by a “firing” nerve cell.

Tizanidine (green circles) activates the α2-adrenergic receptor on the firing nerve cell,

preventing the nerve from releasing more chemicals (red lines).

 

Tizanidine Uses

Tizanidine is primarily used to treat muscle spasticity caused by multiple sclerosis, spinal cord injuries and brain injuries.1

Doctors may also prescribe tizanidine for back pain, migraine headaches and some of the symptoms of fibromyalgia.6

Though it can make you sleepy and relaxed, tizanidine is not recommended as a treatment for sleep disorders or anxiety.1,2

Because tizanidine wears off quickly, you should take tizanidine shortly before engaging in activities that require optimal muscle function or may cause spasticity to become worse.2

 

Tizanidine Dosage

Adult Dosage

Your doctor will tell you how much and how often you need to take tizanidine. What she decides will depend on your age and medical history.1,2

Regardless of the exact dose prescribed to you, you should be aware that1,2:

  • Tizanidine should be taken in divided doses up to a maximum of three times a day.2
  • Your treatment will likely begin with a low dose of 2 mg. If this does not relieve your symptoms, your doctor will gradually increase your dose by 2 mg to 4 mg until it properly relieves your pain and muscle 1,2
  • You should wait at least 6 to 8 hours between doses.2
  • Your total daily dose should never be higher than 36 mg.2

Children

Tizanidine has not been studied in children. Use in individuals younger than 18 years old is not recommended.1,2

Older Adults

Use of tizanidine in adults over 65 years old is usually not recommended. Older adults may be at higher risk for side effects.1

Individuals with Kidney Disease

You should use tizanidine with care if you have kidney disease.1,2 This is because if your kidneys are not working well your body cannot remove the drug from your body as well as it should. Having higher levels of tizanidine in your body can put you at high risk for serious side effects or overdose.1,2

If you have kidney disease, your doctor will likely start you on a very low dosage of tizanidine (2 mg per day) and will monitor your kidney function throughout therapy.1,2

 

 

Tizanidine Administration

Once your doctor selects the appropriate dosage and drug form for you, you should keep in mind that:

  • Tizanidine capsules or tablets should be taken by mouth.1,2
  • Tizanidine can be taken with or without food, but it needs to be taken the same way during the whole treatment. Every time you take tizanidine, you should take it either always with or always without food.2,7
  • Tizanidine in capsule form is absorbed in a different way by the body than in tablets. You should never substitute one product for the other.2,7
  • Tizanidine’s half-life is approximately 2 hours. Therefore, it has maximum effect 1 to 2 hours after you take it. This effect disappears slowly over 3 to 6 hours.2

 

Tizanidine Side Effects

Tizanidine may cause mild and short-term side effects, such as1,2:

  • tiredness and an increased desire to sleep
  • dry mouth
  • dizziness

Rarely, tizanidine may also cause serious side effects. These include:

  • Extremely Low Blood Pressure

Tizanidine may lower your blood pressure. If your blood pressure is too low, you can experience serious symptoms, such as2:

  • dizziness
  • fainting
  • extreme tiredness
  • headaches
  • shortness of breath
  • circulatory collapse

If you have symptoms of low blood pressure that affect your daily life or become severe, talk to your doctor.2

  • Sedation

Tizanidine can cause sedation.2

Sedation is a depression of consciousness, making you less aware of what is happening around you.18 Excessive sedation may affect your ability to carry out your daily activities.2

The effects of tizanidine with other CNS depressants may be additive and may make you feel even more sleepy. Examples of other CNS depressants that may make you drowsier while taking tizanidine include2:

  • alcohol
  • opioid pain medications
  • antidepressants

Talk to your doctor before taking any of the above while you are using tizanidine.2

  • Hallucinations

Tizanidine may cause hallucinations (seeing things that aren’t real) or delusions (believing in things that aren’t real).1,2

This is more likely to happen if you are taking tizanidine at the same time as an anti-depressant.1,2 Tell your doctor if you are taking other drugs while on tizanidine.

If you have symptoms of hallucinations, such as seeing things or hearing voices that do not exist, contact your doctor right away.1,2

  • Liver Damage

Tizanidine can cause liver damage, though this effect is rare at daily doses below 12 mg.1

If you have liver problems, your doctor will likely ask you to do regular blood tests to monitor the way your liver is working. Tizanidine may increase your liver enzymes levels, but they usually return to normal after you stop taking it.1,2

If you have any of the following symptoms contact your doctor immediately. These could be a sign of more serious liver injury19:

  • pain or tenderness in your upper stomach
  • pale stools
  • dark urine
  • loss of appetite
  • nausea and vomiting
  • yellow eyes or skin
  • Allergic Reaction

Tizanidine can cause anaphylaxis, a life-threatening allergic reaction that needs to be treated right away.20

Symptoms of anaphylaxis include20:

  • rash
  • itching
  • trouble breathing or swallowing
  • swelling of your hands, face, or mouth

If any of these symptoms occur, stop taking tizanidine and call 911 immediately.2

 

Warnings for Tizanidine Use

General Warnings

Do not take tizanidine if you are allergic to it or any of its ingredients.2

Do not take tizanidine if you have severe liver damage or liver disease.2

Do not take tizanidine while you are taking fluvoxamine or ciprofloxacin.2

Tizanidine can make some people sleepy, dizzy or faint. If you experience any of these side effect you should stay away from activities that require you to focus, such as driving a car or operating machines.1,2

Warnings for Pregnant Women

The FDA has not studied whether or not tizanidine is safe for use during pregnancy. If you are pregnant or wish to become pregnant should avoid tizanidine unless instructed otherwise by your doctor.1,2

 

Warnings for Nursing Mothers

It is not known whether tizanidine can pass into human milk. Its use is not recommended in women who are nursing.1,2

 

Tizanidine Compared to Other Similar Drugs

 Tizanidine vs. Cyclobenzaprine (Flexeril)

Tizanidine and cyclobenzaprine are both muscle relaxants that reduce tension in your muscles.1,2.9

Tizanidine belongs to the group of drugs used to treat spasticity caused by problems in the central nervous system, such as a spinal cord injury.1,2

Cyclobenzaprine, on the other hand, is not effective against muscle spasms caused by problems with the central nervous system. It is used to treat muscle spasms caused by other conditions.9

If you need to take a muscle relaxant, your doctor will choose the best medicine for you based on the reason for your muscle spasms and your medical history.1,2,9

If you are taking tizanidine, do not switch to cyclobenzaprine or any other muscle relaxants. Always follow the instructions provided by your doctor.9

Tizanidine vs. Methocarbamol (Robaxin)

Tizanidine and methocarbamol are both muscle relaxants. However, they act in different ways and are used for different muscle conditions.1,2,10

Methocarbamol is used to relieve symptoms of muscle spasms caused by painful injuries affecting the muscles, bones, or joints.10

Doctors still do not fully know how methocarbamol works. They think that it may slow down central nervous system signaling, leading to muscle relaxation.10

Unlike tizanidine, methocarbamol is not the first choice in the treatment of spasticity. However, in situations in which tizanidine cannot be used, methocarbamol may be prescribed as an alternative.11

Tizanidine vs. Carisoprodol (Soma)

Carisoprodol (Soma) is also a muscle relaxant. It works differently than tizanidine, however, and is used to treat pain from muscle injuries, rather than from central nervous system conditions.12,13

Unlike tizanidine, carisoprodol has a high risk of abuse.2,12 There have been several cases of illegal abuse of this drug and it is known to be able to cause addiction. For this reason, it should only be used short-term (2 to 3 weeks).12

Never take carisoprodol without a doctor’s supervision.12

Tizanidine vs. Diazepam (Valium)

Diazepam is a tranquilizer that also has the ability to relax your muscles.3,21 It was the first drug found to be effective in treating spasticity, but due to the extreme drowsiness diazepam causes, it is no longer the preferred option for treating this condition.4,8,11

Studies show that there is no significant difference in the effectiveness of tizanidine and diazepam in relieving muscle spasms.8 Your doctor will decide which drug is better for you, based on your health condition and medical history and how you respond to the medications.8,11

 

Tizanidine Drug Interactions

Tizanidine and Alcohol

Alcohol raises the amount of tizanidine in your blood, increasing your risk of side effects.1,2

You should avoid drinking alcohol when you are taking tizanidine.1,2

Tizanidine and Central Nervous System Depressants

Tizanidine has sedative effects. You can experience excess sedation if you take tizanidine and another CNS depressant at the same time. Other commonly used CNS depressants include1,2:

  • tranquilizers
  • antidepressants
  • opioid pain killers
  • alcohol

 

Tizanidine and Cyclobenzaprine (Flexeril)

Cyclobenzaprine is a CNS depressant.22

Taking it with tizanidine can make you more likely to feel dizzy or tired. Never take these two drugs at the same time without your doctor’s permission.1

Tizanidine and Meloxicam

Meloxicam is an anti-inflammatory drug used to relieve inflammation and pain from arthritis.15

Currently, there are no known interactions between tizanidine and meloxicam. However, this does not mean that interactions do not exist.1

You should always consult with your doctor or pharmacist before taking other drugs, such as meloxicam, while you are taking tizanidine.1

Tizanidine and Tramadol

Use of tizanidine and tramadol at the same time is not recommended, as this can cause serious side effects.1,16

Tramadol is a narcotic used to relieve moderate to severe pain. Narcotics suppress your brain function, dull your senses and induce deep sleep.16

Since tizanidine also suppresses your brain function, taking tramadol at the same time can lower your brain function to dangerous levels. It may cause you to stop breathing properly or fall into a coma. These side effects can lead to death.1,16

Do not take tramadol during the treatment with tizanidine and never self-medicate without your doctor’s approval.1,16

Tizanidine and Gabapentin

Gabapentin is an anticonvulsant. It is frequently used in epilepsy, but can also be used to control spasticity.4,14

Gabapentin is a central nervous system depressant.23 Using it together with tizanidine may enhance this effect. It can make you feel dizzy, confused, or lower your blood pressure to unsafe levels. Let your doctor know if you develop these symptoms, if they persist or if they are affecting your daily life.1,14

 

Tizanidine and Oral Birth Control

Oral birth control may notably increase the effects of tizanidine. Use of tizanidine with birth control pills should be avoided.

Tell your doctor if you are taking birth control pills before taking tizanidine. If you must take both of these drugs at the same time, watch out for adverse reactions such as1,2:

  • low blood pressure
  • low heart rate

 

Tizanidine Abuse and Dependence

Currently, there is no clinical data available on the abuse or addictive potential of tizanidine.2

Tizanidine is, however, able to cause dependence. If you stop taking tizanidine suddenly, you can experience withdrawal symptoms, such as1,2:

  • high blood pressure
  • increased heart rate
  • tremor
  • anxiety

These symptoms are more likely to occur if you have been taking high doses of tizanidine (20 mg to 36 mg daily) or taking it for a long period of time (9 weeks or longer).1,2

 

Tizanidine Overdose

If you take too much tizanidine, you may experience clinical symptoms of tizanidine overdose, including2:

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

If you accidentally take more tizanidine than your doctor prescribed for you or experience any severe symptoms, call 911 or go to the nearest emergency room.2

 

Storage and Disposal of Tizanidine

Storage

  • Keep tizanidine in the container it came in, tightly closed.1,2
  • Store it in a safe location, out of reach and sight of children.1,2
  • Store it at room temperature [25°C (77°F)]. Variations in temperature are permitted from 15°C to 30°C (59°F to 86°F), as long as they happen only for a short period of time.1,2
  • Don’t store it in hot and moist areas, such as your bathroom.7

Disposal7

  • If you have drugs at home that you don’t need anymore, you should not flush them down the toilet or put them in the trash.
  • Expired or unneeded drugs should be transferred to authorized collectors for disposal. You can usually find these in a pharmacy.
  • If you don’t know how to throw away a drug that you no longer need, please contact your local pharmacy.

 

Other Important Information

Take tizanidine exactly as prescribed. Never stop taking it without talking to your doctor.7

If you miss a dose of tizanidine, do not take a double dose to make up for the missed one. If it is almost time for your next dose, skip the missed dose and take your next dose at the normal time.7

If you have any questions about the use of tizanidine, ask your doctor or pharmacist.2

 

Tizanidine FAQs

  • Is tizanidine a narcotic?

Tizanidine is not a narcotic, it is a muscle relaxant with a different mechanism of action.1

Narcotics are a group of medicines used to relieve severe pain. They act on opioid receptors, which can cause addiction and dependence. Examples of narcotics are morphine and codeine.17

  • How does Zanaflex make you feel?

Because tizanidine relaxes your muscles, it may make you feel weak or clumsy.1,2

And since it depresses your central nervous system, it may also make you feel drowsy, sleepy, or dizzy.1,2

  • What is the maximum dose of Zanaflex?

The maximum single dose of Zanaflex is 16 mg and the maximum daily dose of Zanaflex is 36 mg.2

However, you should never take more Zanaflex than your doctor has prescribed for you. This is the dose your doctor determined is safest for you and any dose greater than this may put you at greater risk for serious side effects or overdose.1,2

  • How much tizanidine is needed to overdose?

You shouldn’t exceed a daily dose of 36 mg of tizanidine, divided into three doses a day. Doses higher than this damage your liver.2

The amount of tizanidine needed to cause an acute, fatal overdose has not been defined.2

  • Do muscle relaxers lower blood pressure?

Tizanidine can lower your blood pressure. If you’re taking tizanidine, you can be at high risk for experiencing the symptoms of low blood.

You can minimize your risk of severe dizziness or fainting by getting up slowly from sitting or lying postions.2

  • Is tizanidine a controlled substance?

Tizanidine is not a controlled substance, but it is available only with a doctor’s prescription.1,2

 

  • Where can I buy tizanidine from?

You can buy tizanidine at any pharmacy with a prescription from your doctor.1,2

 

 

REFERENCES

  1. Teva UK Ltd. Summary Of Product Characteristics – Tizanidine. 2016. Available at: http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1470373869002.pdf. Accessed September 9, 2017.
  2. Acorda Therapeutics Inc. Zanaflex®. 2013. Available at: http://www.acorda.com/assets/docs/zanaflexpi-final-fda-approved-subm111813.pdf Accessed September 9, 2017.
  1. US Food and Drug Administration – FDA. General Drug Categories. Available at: https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/ucm176533.htm Accessed September 9, 2017.
  1. Chou R, Peterson K. Drug Class Review: Skeletal Muscle Relaxants: Final Report. Portland: Oregon Health & Science University; 2005. Available at: https://www.ncbi.nlm.nih.gov/books/NBK10690/pdf/Bookshelf_NBK10690.pdf
  2. National Multiple Sclerosis Society. MS Symptoms – Spasticity. Available at: http://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms/Spasticity. Accessed September 9, 2017.
  3. Dilshad, H, Naveed, S, Ahad, S. Comparative Study of Different Brands of Tizanidine. International Journal of Pharmaceutical Research & Drug Development. 2014;1(2):1-8. Available at: https://www.researchgate.net/profile/Safila_Naveed/publication/266390433_Comparitive_Study_of_Different_Brands_of_Tizanidine/links/5430227d0cf277d58e959b65.pdf.
  4. The American Society of Health-System Pharmacists, Inc. Tizanidine. AHFS® Patient Medication Information. Bethesda, Maryland. Available at: https://medlineplus.gov/druginfo/meds/a601121.html. Accessed September 9, 2017.
  5. National Institute for Health and Care Excellence (UK). Multiple Sclerosis: Management of Multiple Sclerosis in Primary and Secondary Care. Chapter 9: Pharmacological management of MS symptoms. NICE Clinical Guidelines, No. 186. 2014. London. Available at: https://www.ncbi.nlm.nih.gov/books/NBK328181/. Accessed September 9, 2017.
  6. ALZA Corporation. Summary of Product Characteristics – FLEXERIL® (Cyclobenzaprine HCL). 2001. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/017821s045lbl.pdf. Accessed September 9, 2017.
  7. Almirall, S.A. Summary of Product Characteristics – Robaxin-750 (Methocarbamol). 2017. Available at: http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1501824345437.pdf. Accessed September 9, 2017.
  8. Saulino, M., Jacobs, B. The Pharmacological Management of Spasticity. J Neurosci Nurs. 2006;38(6):456-459. Available at: http://www.medscape.com/viewarticle/552267_3. Accessed September 17, 2017.
  9. Meda Pharmaceuticals Inc. Soma® compound. 2009. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/012365s038lbl.pdf. Accessed September 9, 2017.
  10. European Medicines Agency. Press Release – European Medicines Agency recommends suspension of marketing authorisations for carisoprodol-containing medicinal products. 2007. Available at: http://www.emea.europa.eu/pdfs/human/press/pr/Pressrelease_Carisoprodol_52046307en.pdf. Accessed September 9, 2017.
  11. Sandoz Limited. Summary Of Product Characteristics – Gabapentin 100 mg capsules. 2017. Available at: http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1490936684194.pdf. Accessed September 9, 2017.
  1. Actavis UK Limited. Summary Of Product Characteristics – Meloxicam 15 mg tablets. 2016. Available at: http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1505451268327.pdf. Accessed September 17, 2017.
  2. Milpharm Limited. Summary Of Product Characteristics – Tramadol 50 mg capsules. 2017. Available at: http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1500616148852.pdf. Accessed September 9, 2017.
  3. Gioviannitti JA Jr, Thoms SM, and Crawford JJ. Alpha-2 androgenic receptor agonists: a review of current clinical applications. Anesthesia Progress. 2015;62(1):31-38. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389556/.
  4. Morita T, Tsuneto S, and Shima Y. Definition of sedation for symptom relief: a systematic review and proposal of operational criteria. Journal of Pain and Symptom Management. 2002;14(4):447-453. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12505214.
  5. Liver Disease Symptoms. Mayo Clinic. Last updated: July 15, 2014. https://www.mayoclinic.org/diseases-conditions/liver-problems/basics/symptoms/con-20025300. Accessed November 2, 2017.
  6. Anaphylaxis. Mayo Clinic. Last update: February 14, 2017. https://www.mayoclinic.org/diseases-conditions/anaphylaxis/symptoms-causes/syc-20351468. Accessed November 2, 2017.
  7. Roche Pharmaceuticals. Valium prescribing information. Last updated: January 2008. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013263s083lbl.pdf. Accessed November 2, 2017.
  8. McNeil Consumer & Specialty Pharmaceuticals. Flexeril (Cyclobenzaprine HCL) tablets: prescribing information. Last updated: 2001. https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/017821s045lbl.pdf. Accessed November 2, 2017.
  9. Pfizer, Inc. Neurontin prescribing information. Last updated: April 2009. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020235s041,020882s028,021129s027lbl.pdf. Accessed November 2, 2017.

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