Introduction
Pain from fibromyalgia can be quite bothersome. Often, it can have a severe impact on your quality of life, making even normal tasks difficult. Two muscle relaxants called Zanaflex and Flexiril (cyclobenzaprine) are among the drugs used to treat fibromyalgia. Learn how they compare.
Drug features
Flexeril was one popular brand name for the drug cyclobenzaprine. Although the brand Flexeril is no longer available, many doctors still use its name to refer to cyclobenzaprine. Cyclobenzaprine likely treats fibromyalgia by increasing the effects of norepinephrine, a substance in your brain and spinal cord that helps reduce pain signals.
Zanaflex is the brand name for the drug tizanidine. It’s believed to work by reducing the release of substance P in your brain and spinal cord. Substance P is a chemical that helps increase pain signals to and from the brain.
Both of these drugs work to treat fibromyalgia pain and decrease muscle spasms.
The table below summarizes other drug features of both tizanidine and cyclobenzaprine.
| Brands | Zanaflex | Flexiril (Amrix)* |
| What is the generic name? | tizanidine | cyclobenzaprine |
| Is a generic version available? | yes | yes |
| What does it treat? | fibromyalgia pain | fibromyalgia pain |
| What forms does it come in? | oral capsule, oral tablet | oral tablet, extended-release oral capsule |
| What strengths does this drug come in? | oral tablet: 2 mg, 4 mg; oral capsule: 2 mg, 4 mg, 6 mg | oral tablet: 5 mg, 7.5 mg, 10 mg; extended-release oral capsule: 15 mg, 30 mg |
| How do I store it? | at controlled room temperature between 59°F and 86°F (15°C and 30°C) | at controlled room temperature between 59°F to 86°F (15°C to 30°C) |
| Is there a risk of withdrawal with this drug? | yes† | yes† |
| Does this drug have potential for misuse? | yes†† | yes†† |
† If you’ve been taking this drug for longer than a few weeks, don’t stop taking it without talking to your doctor. You’ll need to taper off the drug slowly to avoid withdrawal symptoms such as anxiety, sweating, nausea, and trouble sleeping.
†† A high misuse potential means you can get addicted to this drug. Be sure to take it exactly as your doctor tells you to. If you have questions or concerns, talk with your doctor.
Alcohol and withdrawal risks
Do not drink alcohol while using either tizanidine or cyclobenzaprine. Drinking alcohol with either drug may cause severe drowsiness and make you much less alert. This effect can make activities such as driving difficult and unsafe.
You also should not stop taking tizanidine or cyclobenzaprine suddenly. Doing so can cause withdrawal symptoms. This is especially likely if you’ve been taking either drug for a long time.
Withdrawal symptoms of tizanidine include:
- high blood pressure
- fast heart rate
- increased muscle tone
- tremors
- anxiety
Withdrawal symptoms of cyclobenzaprine include:
- nausea
- headache
- tiredness
If you need to stop taking either drug, your doctor will slowly lower your dosage over time.
Cost, availability, and insurance
Tizanidine and cyclobenzaprine are both available as brand-name and generic drugs. Generally, the brand-name drugs are more expensive than the generics. Between the generics, tizanidine is more expensive than cyclobenzaprine. Both drugs are available in most pharmacies.
Health insurance plans usually cover the generic forms of both drugs without prior authorization. In many cases, insurance companies will require a prior authorization for Zanaflex or Amrix.
Side effects
Tizanidine and cyclobenzaprine cause similar side effects. The chart below compares examples of side effects of both drugs.
| Common side effects | Tizanidine | Cyclobenzaprine |
| dry mouth | X | X |
| drowsiness | X | X |
| dizziness | X | X |
| weakness or lack of energy | X | X |
| constipation | X | X |
| nervousness | X | X |
| urinary tract infection | X | |
| vomiting | X | |
| abnormal liver function test results | X | |
| headache | X | |
| confusion | X | |
| nausea | X | |
| indigestion | X | |
| unpleasant taste | X | |
| speech disorders | X | |
| blurry vision | X | X |
| needing to urinate more often than normal | X | |
| flu-like symptoms | X | |
| trouble performing voluntary movements | X |
These drugs also have shared serious side effects, including:
- heart rhythm changes
- low blood pressure
- liver problems
- severe allergic reactions (may cause a rash, itching, swelling of your throat, or trouble breathing)
In rare cases, liver problems from these drugs may cause hepatitis (inflammation of your liver) and jaundice ( yellowing of your skin and whites of eyes).
Tizadinine can also cause extreme drowsiness and hallucinations (seeing or hearing things that aren’t real) or delusions (false beliefs). Additionally, cyclobenzaprine can cause:
- serotonin syndrome, with symptoms such as confusion, hallucinations, agitation, sweating, higher body temperature, tremors, seizures, stiff muscles, nausea, vomiting and diarrhea
- urinary problems, such as not being able to urinate or to fully empty your bladder
- seizures
Drug interactions
Tizanidine and cyclobenzaprine can interact with certain other drugs. For instance, both drugs interact with central nervous system (CNS) stimulants like alcohol, narcotics, and benzodiazepines. Taking either tizanidine or cyclobenzaprine with a CNS stimulant can cause intense drowsiness. Both drugs also interact with certain high blood pressure drugs.
Here are examples of other drugs that may interact with tizanidine and cyclobenzaprine.
| Tizanidine | Cyclobenzaprine |
| CNS depressants such as benzodiazepines, opioids, and tricyclic antidepressants | CNS depressants such as benzodiazepines, opioids, and tricyclic antidepressants |
| high blood pressure drugs such as clonidine, guanfacine, and methyldopa | high blood pressure drugs such as clonidine, guanfacine, and methyldopa |
| heart rhythm drugs such as amiodarone, mexiletine, propafenone, and verapamil | monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, and isocarboxazid |
| antibiotics such as levofloxacin, moxifloxacin, and ofloxacin | certain depression and anxiety drugs |
| oral contraceptives (birth control pills) | pain drugs such as tramadol or meperidine |
| ciprofloxacin | bupropion |
| fluvoxamine | verapamil |
| cimetidine | |
| famotidine | |
| zileuton | |
| acyclovir | |
| ticlopidine |
Use with other medical conditions
Both tizanidine and cyclobenzaprine can cause problems if you take them when you have certain other health issues. You should avoid using either of these drugs if you:
- have liver disease
- are pregnant or breastfeeding
- have a slow heart rhythm or heart rhythm problems
You should also discuss the safety of tizanidine if you have kidney disease or low blood pressure. Talk to your doctor about the safety of cyclobenzaprine if you have:
- hyperthyroidism
- recent heart attack
- heart failure
- seizure disorder
Talk with your doctor
Tizanidine and cyclobenzaprine are muscle relaxants that help treat muscle pain from fibromyalgia. Objectively, one medication is not clearly more effective than the other. Your doctor will choose the best drug for you based on factors like your health and any other medications you’re taking.


