Introduction
Pain from fibromyalgia can have a severe impact on your quality of life, making even normal tasks difficult.
Two muscle relaxants called Zanaflex and Flexeril are among the drugs used to treat fibromyalgia. These drugs aren’t approved by the Food and Drug Administration (FDA) for treating fibromyalgia, but both are commonly prescribed as an off-label medication. Learn how they compare.
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 attaching to a receptor or protein in the brain called the alpha-2 receptor, which reduces 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 | Flexeril (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 |
* Cyclobenzaprine is no longer sold under the brand name Flexeril.
Don’t 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 shouldn’t stop taking tizanidine or cyclobenzaprine suddenly. Doing so may cause withdrawal symptoms. This is especially likely if you’ve been taking either drug for a long time.
Withdrawal symptoms of tizanidine include:
Withdrawal symptoms of cyclobenzaprine include:
If you need to stop taking either drug, talk to your doctor. They may slowly lower your dosage over time.
Although not common, in some cases tizanidine and cyclobenzaprine have been misused or abused. Be sure to take either drug exactly as your doctor tells you to. If you have questions or concerns, talk with your doctor.
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 may be slightly 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 (a current brand name for extended-release cyclobenzaprine).
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 | |
| 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).
Tizanidine 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
Tizanidine and cyclobenzaprine can interact with certain other drugs.
For instance, both drugs interact with central nervous system (CNS) depressants like alcohol, narcotics, and benzodiazepines. Taking either tizanidine or cyclobenzaprine with a CNS depressant 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 antidepressant and antianxiety medications |
| oral contraceptives (birth control pills) | pain drugs such as tramadol or meperidine |
| ciprofloxacin | bupropion |
| fluvoxamine | verapamil |
| cimetidine | |
| famotidine | |
| zileuton | |
| acyclovir | |
| ticlopidine |
Both tizanidine and cyclobenzaprine can cause problems if you take them when you have certain other health issues. You should avoid using cyclobenzaprine if you have a slow heart rhythm or heart rhythm problems. In some circumstances, tizanidine might be used safely in this case.
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
- liver disease (depending on the type)
If you are pregnant or breastfeeding, you should also discuss using cyclobenzaprine with your healthcare provider.
Tizanidine and cyclobenzaprine are muscle relaxants that help treat muscle pain from fibromyalgia. The effectiveness of these medications hasn’t been compared in clinical studies, so we don’t know if one is more effective than the other.
However, there is much more clinical research on the effects of cyclobenzaprine for fibromyalgia than tizanidine. Usually the better studied drugs are used first.
Your doctor will choose the best drug for you based on factors like your health and any other medications you’re taking.