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Drug vs. Drug

Zanaflex vs. Flexeril: Differences, similarities, and which is better for you

Gerardo Sison medical writer headshot By | Updated on May 7, 2020

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Brand-name Flexeril has been discontinued; however, it is still available as a generic—cyclobenzaprine—and as brand names Amrix and Fexmid.

Zanaflex (tizanidine) and Flexeril (cyclobenzaprine) are muscle relaxants used to treat painful musculoskeletal conditions. If you experience neck or back strains, you may be recommended a muscle relaxant like Zanaflex or Flexeril. These drugs can also help relieve muscle spasms and stiffness related to other physical conditions and injuries.

Like other muscle relaxants, Zanaflex and Flexeril work in the central nervous system (CNS). They also have similar side effects and costs. However, they have differences in how they’re used and formulated.

What are the main differences between Zanaflex and Flexeril?


Zanaflex is the brand name for tizanidine and acts as an alpha-2 adrenergic agonist. It was initially approved in 1996 for the treatment of muscle spasticity. Although its exact mechanism of action is unknown, it is believed to manage muscle spasticity through the inhibition of motor nerve signals.

Zanaflex is available as an oral tablet in strengths of 2 mg and 4 mg. It also comes as an oral capsule in strengths of 2 mg, 4 mg, and 6 mg. Zanaflex is usually taken up to three times per day.


Flexeril is a brand-name drug originally FDA-approved in 1977. The generic version of Flexeril, cyclobenzaprine, is widely available. Flexeril is structurally similar to tricyclic antidepressants and primarily works in the central nervous system (CNS). It helps reduce muscle hyperactivity through actions on the gamma- and alpha-motor systems.

Cyclobenzaprine is no longer available as Flexeril. Instead, cyclobenzaprine can be found under different brand names: Amrix (extended-release) and Fexmid (immediate-release). Immediate-release cyclobenzaprine is taken up to three times per day while the extended-release form can be taken once daily.

Main differences between Zanaflex and Flexeril
Zanaflex Flexeril
Drug class Muscle relaxant Muscle relaxant
Brand/generic status Brand and generic version available Brand and generic version available

Brand name Flexeril has been discontinued in the U.S. Other brand names include Amrix and Fexmid.

What is the generic name? Tizanidine Cyclobenzaprine
What form(s) does the drug come in? Oral tablet
Oral capsule
Oral tablet
Oral capsule, extended-release
What is the standard dosage? Initial dose of 2 mg, followed by subsequent doses every 6 to 8 hours. Maximum of 3 doses in 24 hours.

Dosage may be increased every 1 to 4 days by 2 mg to 4 mg. Maximum daily dose of 36 mg.

Immediate-release tablets: 5 mg to 10 mg three times daily.

Extended-release capsules: 15 mg to 30 mg once daily.

How long is the typical treatment? Short-term or long-term duration depending on the condition No more than 2 to 3 weeks
Who typically uses the medication? Adults aged 18 years and older Adults and young adults aged 15 years and older


Conditions treated by Zanaflex and Flexeril

Both Zanaflex and Flexeril are drugs used for muscle spasms and pain relief from musculoskeletal conditions. Zanaflex is commonly prescribed to treat spasticity from multiple sclerosis, cerebral palsy, and spinal cord injury. Flexeril is often prescribed to relieve muscle pain and spasms caused by back and neck strains.

Zanaflex and Flexeril are sometimes prescribed off-label to treat fibromyalgia and migraines. Often combined with other drugs, Zanaflex or Flexeril can also help manage muscle stiffness and tremors associated with tetanus.

Condition Zanaflex Flexeril
Muscle spasms Yes Yes
Musculoskeletal conditions Yes Yes
Tetanus Yes Yes
Fibromyalgia Off-label Off-label
Migraines Off-label Off-label

Is Zanaflex or Flexeril more effective?

Zanaflex and Flexeril are both effective drugs for muscle spasms and muscle pain. Their use depends on which one is more suitable on a case-by-case basis. Currently, there is no clinical data showing a direct comparison between these two drugs.

According to a meta-analysis, cyclobenzaprine has been studied in the most clinical trials with evidence to support its use. Tizanidine was shown to be effective for spasticity due to multiple sclerosis. Both cyclobenzaprine and tizanidine were found to be effective for musculoskeletal conditions such as acute neck or back pain.

The meta-analysis assessed over 100 different trials comparing several muscle relaxants, including Lioresal (baclofen), Soma (carisoprodol), Robaxin (methocarbamol), Skelaxin (metaxalone), and Valium (diazepam). Overall, the study found that these drugs are comparable in efficacy and safety. Other guidelines suggest that muscle relaxants cause increased drowsiness and should only be used short-term.

Drugs like Zanaflex and Flexeril are often recommended along with physical therapy to relieve pain. Consult a healthcare provider to determine the best treatment option for you.

Coverage and cost comparison of Zanaflex vs. Flexeril

Generic Zanaflex is typically covered by most Medicare and insurance plans. The quantity prescribed will vary depending on the strength of the drug and your doctor’s instructions. The average retail cost of Zanaflex is around $56. With a Zanaflex discount coupon, the retail cost can be less than $10 for 30, 4 mg tablets.

Flexeril is also covered by most Medicare and insurance plans when it’s prescribed as a generic. Immediate-release tablets are commonly prescribed to be taken multiple times per day. The average retail cost for a cyclobenzaprine prescription can run around $42. You can also take advantage of a Flexeril coupon to get a reduced price of around $7 at a participating pharmacy.

  Zanaflex Flexeril
Typically covered by insurance? Yes Yes
Typically covered by Medicare? Yes Yes
Standard dosage 4 mg tablet every 6 to 8 hours 10 mg tablet three times daily
Typical Medicare copay $0–$41 $1–$35
SingleCare cost $9+ $7+

Common side effects of Zanaflex vs. Flexeril

The most common side effects of Zanaflex include dry mouth, drowsiness, dizziness, muscle weakness or fatigue, and constipation. Other reported side effects include urinary tract infections (UTIs) and involuntary movements (dyskinesia).

The most common side effects of Flexeril include drowsiness, dry mouth, headache, fatigue, and dizziness. Flexeril is also known to cause other side effects such as constipation and nausea.

  Zanaflex Flexeril
Side Effect Applicable? Frequency Applicable? Frequency
Drowsiness Yes 48% Yes 29%
Dry mouth Yes 49% Yes 21%
Headache No Yes 5%
Fatigue Yes 41% Yes 6%
Dizziness Yes 16% Yes 1%–3%
Nausea No Yes 1%–3%
Constipation Yes 4% Yes 1%–3%
UTI Yes 10% No
Involuntary movements Yes 3% No

This may not be a complete list of adverse effects that can occur. Please refer to your doctor or healthcare provider to learn more.
Source: DailyMed (Zanaflex), DailyMed (Flexeril)

Drug interactions of Zanaflex vs. Flexeril

Zanaflex is mainly processed by the CYP1A2 enzyme in the liver. Drugs that block, or inhibit, this enzyme can increase Zanaflex levels in the body. Increased drug levels can lead to increased adverse effects such as drowsiness and dizziness. Zanaflex should be avoided with CYP1A2 inhibitors like ciprofloxacin and cimetidine as well as birth control pills containing ethinyl estradiol.

Flexeril can interact with serotonergic drugs like antidepressants and MAO inhibitors. Taking these drugs with Flexeril can increase the risk of serotonin syndrome, a condition that requires immediate medical attention.

Both Zanaflex and Flexeril can interact with drugs that have CNS depressant effects. These types of drugs include barbiturates, opioids, and benzodiazepines. Zanaflex and Flexeril can enhance their effects and lead to increased dizziness and sedation.

Drug Drug Class Zanaflex Flexeril
CYP1A2 inhibitors Yes No
Ethinyl estradiol
Oral contraceptives Yes No
Monoamine oxidase inhibitors (MAOIs) No Yes
Tricyclic antidepressants No Yes
Barbiturates Yes Yes
Opioids Yes Yes
Benzodiazepines Yes Yes

*Consult a healthcare professional for other drug interactions

Warnings of Zanaflex and Flexeril

Zanaflex has the potential to cause hypotension or abnormally low blood pressure. This effect typically manifests as orthostatic hypotension which occurs when a person moves to an upright position after lying down. In excess doses, Flexeril is also known to cause changes in blood pressure.

Zanaflex may cause liver injury in some people, especially those who have a history of liver impairment. Flexeril should also be used with caution in individuals with liver problems.

Flexeril is known to cause serotonin syndrome, especially when taken with certain antidepressants, MAO inhibitors, and opioids. Signs and symptoms of serotonin syndrome should be monitored when starting treatment with Flexeril.

Frequently asked questions about Zanaflex vs. Flexeril

What is Zanaflex?

Zanaflex, or tizanidine, is a muscle relaxant used to treat muscle spasticity due to multiple sclerosis and spinal cord injury. It works by blocking signals between motor nerves to relax muscle tone. It is usually taken as a 2 mg or 4 mg tablet every six to eight hours.

What is Flexeril?

Flexeril is the brand name for cyclobenzaprine. It is a muscle relaxant indicated for acute, painful musculoskeletal conditions such as neck or back pain. It works in the central nervous system (CNS) to relieve muscle pain and spasms. Cyclobenzaprine is available in immediate-release and extended-release forms.

Are Zanaflex and Flexeril the same?

Zanaflex and Flexeril are not the same. Zanaflex has a half-life of around 2.5 hours while Flexeril has a half-life of 18 hours on average. Zanaflex only comes in immediate-release oral tablets and capsules while Flexeril comes in an extended-release capsule.

Is Zanaflex or Flexeril better?

Zanaflex is a newer drug FDA-approved for muscle spasticity due to multiple sclerosis and spinal cord injuries. Flexeril is an older drug that has been more heavily studied for musculoskeletal pain and spasms. The better drug is the one that works best for your specific condition. Consult a doctor to help find the best option for you.

Can I use Zanaflex or Flexeril while pregnant?

Zanaflex may be harmful to the unborn baby according to animal studies. There have been no adequate animal or human studies that show Flexeril is harmful while pregnant. Muscle relaxers should only be used if there are clear benefits that outweigh potential risks. Seek medical advice from your healthcare provider for treatment options while pregnant.

Can I use Zanaflex or Flexeril with alcohol?

Drinking alcohol while taking Zanaflex or Flexeril can enhance the sedative effects of these drugs. It is not generally recommended to drink alcohol with muscle relaxants.

Is tizanidine better than cyclobenzaprine?

Tizanidine may be preferred for muscle spasms caused by multiple sclerosis, cerebral palsy, and spinal cord injury. Cyclobenzaprine is used along with physical therapy and rest to relieve pain and muscle spasms.

Is Zanaflex addictive?

Zanaflex is not a controlled substance according to the DEA. However, like other muscle relaxers, it can be abused by some people. Zanaflex is considered a short-term treatment option. Abuse and dependence may occur with long-term use and lead to addictive habits.

Does Flexeril help with pain?

Flexeril may indirectly relieve pain associated with muscle spasms. Depending on what’s causing the pain, your doctor may first recommend an over-the-counter drug like acetaminophen or ibuprofen.