Cyclobenzaprine (Flexeril®)

Cyclobenzaprine in Brief
  • Generic name: Cyclobenzaprine hydrochloride
  • Brand names: Flexeril®, Fexmid®
  • Drug class: Skeletal Muscle Relaxant
  • FDA Approved: August 26, 1977
  • Pregnancy Category: B
  • Habit forming? No
  • Originally discovered: 1961, Merck and Co, USA USA

Based on "Essential Pain Pharmacology"
written by Howard S. Smith, MD; Marco Pappagallo, MD


Cyclobenzaprine hcl is a long-acting skeletal muscle relaxant which relieves muscle spasms and improves signs and symptoms such as pain, tenderness, limitation of motion, and restriction in activities of daily living. It is closely related to the first-generation tricyclic antidepressants.

The principal side effects of cyclobenzaprine are drowsiness, dry mouth or tongue, dizziness and bad taste.



Cyclobenzaprine after its synthesis in 1961 was found to have limited antidepressant action with no significant advantage over other tricyclics. However it was found to act as a centrally acting muscle relaxant and has been widely used ever since.

Cyclobenzaprine was approved by the U.S. Food and Drug Administration in 1977 for the treatment of acute muscle spasms of local origin. Cyclobenzaprine is sold as a hydrochloride salt in a 10 mg non-scored tablet under the trade name Flexeril (Merck and Co.) or as a generic (Genera, Warner-Chilcott, Duramed, Mylan, Endogenerics, and Watson).

Once-a-day extended release formulation, Amrix, has been approved by the FDA in 2007 and is available in 15 and 30 mg capsules.

FDA approved uses

  • Adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions

A muscle spasm is an uncontrollable contraction of a muscle. Cyclobenzaprine only works to relieve muscle spasms caused by problems in the muscles. It is ineffective in muscle spasm due to central nervous system disease.

Off-label & Investigational uses

  • Fibromyalgia1, 3
    Cyclobenzaprine may be helpful for sleep and pain control in fibromyalgia.
    The usual starting dose is 5-10 mg taken at bedtime. The dose may be increased to 20-30 mg, taken either at night or in divided doses during the day. Compared with amitriptyline, cyclobenzaprine is associated with better patient acceptance due to fewer side effects and more rapid onset of relief.
    Cyclobenzaprine has been studied in the treatment of fibromyalgia. In a study of 120 fibromyalgia patients, those receiving Cyclobenzaprine (10 to 40 mg) over a 12 week period had significantly improved quality of sleep and pain score. Interestingly, there was also a reduction in the total number of tender points and muscle tightness.
    A meta-analysis of cyclobenzaprine showed that it was superior to placebo for treating fibromyalgia but that it was not as effective as antidepressants.
  • Tension headaches2
    In a 1972 double-blind study, 10 of 20 patients receiving cyclobenzaprine experienced a 50% or greater improvement in tension-type headache, compared with only 5 of 20 patients receiving placebo. The usual dose of cyclobenzaprine is 10 mg at bedtime.
  • Insomnia
  • Migraine
  • Levator ani syndrome
  • Tinnitus 4
    Cyclobenzaprine may attenuate some forms of tinnitus, e.g. noise-induced tinnitus.

Cyclobenzaprine "pros" and "cons"


  • Effective. Quick and lasting symptoms relief (back pain, neck pain, muscle spasms)
  • The best-studied muscle relaxant in the treatment of musculoskeletal conditions
  • No potential for abuse and dependence.
  • May be useful in patients with insomnia because of severe muscle spasms.
  • Pregnancy category B. Cyclobenzaprine is considered to be safe during pregnancy.


  • Sedation. Commonly causes drowsiness and dizziness, which may interfere with your daily activity. Even if you take cyclobenzaprine just at bedtime, you may experience a hangover-like effects in the morning and during the daytime because the drug has a long half-life of 24 hours and may accumulate after multiple dosing.
  • Life-threatening interactions with MAO inhibitors.
  • Toxic potential similar to tricyclic antidepressants. Cyclobenzaprine shares the toxic potentials of the tricyclic antidepressants, including prolongation of conduction time, arrhythmias, and tachycardia.
  • Elderly patients can be particularly sensitive to sedating and cognitive effects of cyclobenzaprine.

Mode of action

Onset of action: 1 h.

Duration of action: 12 to 24 h.

Cyclobenzaprine is a muscle relaxant acting primarily on the central nervous system. It is structurally similar to amitriptyline, differing by only one double bond. Cyclobenzaprine is a weak inhibitor of presynaptic norepinephrine and serotonin. Skeletal muscle relaxant activity is due to brainstem mediated inhibition of gamma motor neurons.

Time for Cyclobenzaprine to clear out the system

Cyclobenzaprine is eliminated quite slowly, with an effective half-life of 18 hours. It usually takes 4-5 days to leave the system.


Further reading


  • 1. See S, Ginzburg R. Choosing a skeletal muscle relaxant. Am Fam Physician. 2008 Aug 1;78(3):365-70. PubMed
  • 2. Lance JW, Anthony M. Cyclobenzaprine in the treatment of chronic tension headache. Med J Aust. 1972 Dec 16;2(25):1409-11.
  • 3. Moldofsky H. Management of sleep disorders in fibromyalgia. Rheum Dis Clin North Am. 2002 May;28(2):353-65. PubMed
  • 4. Vanneste S, Figueiredo R, De Ridder D. Treatment of tinnitus with cyclobenzaprine: an open-label study. Int J Clin Pharmacol Ther. 2012 May;50(5):338-44. PubMed

Published: October 05, 2008
Last updated: February 01, 2017

Interesting facts
Cyclobenzaprine facts
  • Muscle relaxants account for approximately 18.5% of all prescriptions written for chronic back pain in the United States.
  • Stretching along with the medicine may provide about 90% relief from pain and tension, and the relief lasts longer than medicine's effect alone.
More Facts
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