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Cyclobenzaprine 3D.gif
Systematic (IUPAC) name
3-(5H-dibenzo[a,d]cyclohepten-5-ylidene)- N,N-dimethyl-1-propanamine
Clinical data
Trade names Amrix (former Flexeril)
AHFS/ Monograph
MedlinePlus a682514
  • Category B
Routes of
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 33% to 55% [1][2]
Metabolism hepatic
Biological half-life 18 hours (range 8–37 hours; n=18)
Excretion renal
CAS Number 303-53-7 YesY
ATC code M03BX08 (WHO)
PubChem CID 2895
DrugBank DB00924 YesY
ChemSpider 2792 YesY
KEGG D07758 YesY
Chemical data
Formula C20H21N
Molar mass 275.387 g/mol

Cyclobenzaprine, brand name Flexeril among others, is a muscle relaxer medication used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions.[3] It is the best-studied drug for this application.[4] It has also been used off-label for fibromyalgia treatment.[5]

As of 2015 the cost for a typical course of medication in the United States is less than $25.[6]

Medical use[edit]

After sustaining an injury, muscle spasms may occur to stabilize the affected body part and prevent further damage. They also generate pain. Cyclobenzaprine is FDA-approved to treat such muscle spasms associated with acute, painful musculoskeletal conditions.[3] It decreases pain in the first two weeks,[4][7] peaking in the first few days, but has no proven benefit after two weeks.[4][8] Since no benefit is proven beyond that, therapy should not be continued long-term.[9] It is not useful for spasticity due to neurologic conditions such as cerebral palsy.[9][10]

Cyclobenzaprine has also shown effectiveness in the treatment of fibromyalgia symptoms, with a report of 4.8 patients needing treatment for each (1) patient reporting pain reduction (but no change in fatigue or tender points).[11]

Some experts believe that cyclobenzaprine should be avoided in elderly patients, because it can cause confusion, delirium, and cognitive impairment.[12][13]

Side effects[edit]

Meta-analysis studies have found significantly increased rates of drowsiness (38% of patients), dry mouth (24%), dizziness (10%), and adverse events of any kind in patients taking cyclobenzaprine versus placebo.[8] Drowsiness and dry mouth appear to intensify with increasing dose.[14]

The sedative effects of cyclobenzaprine are likely due to its antagonistic effect on histamine, serotonin, and muscarinic receptors. Agitation is a common side effect observed especially in the elderly. In general, the National Committee for Quality Assurance recommends avoiding the use of cyclobenzaprine in the elderly because of the potential for more severe side effects.[15] Treatment protocols and support should follow the same as for any structurally related tricyclic, such as tricyclic antidepressants.[16]


The most common effects of overdose are drowsiness and tachycardia.[3] Rare but potentially critical complications are cardiac arrest, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome.[3] Life-threatening overdose is rare,[3] however, as the median lethal dose is about 338 mg/kg in mice and 425 mg/kg in rats.[3] The potential harm is increased when central nervous system depressants and antidepressants are also used; deliberate overdose often includes alcohol among other drugs.[3]


Cyclobenzaprine has major contraindications with monoamine oxidase inhibitors (MAOIs). At least one study also found increased risk of serotonin syndrome when cyclobenzaprine was taken with the serotonergic drugs duloxetine or phenelzine.[17]

These substances may interact with cyclobenzaprine:

If co-administered with opioids, the dose of one or both medicines should be reduced accordingly. The patient should be monitored for excessive sedation.

Comparison to other medications[edit]

Cyclobenzaprine has been found to be not inferior to tizanidine, orphenadrine, and carisoprodol in the treatment of acute lower back pain, although none has been proven to be effective for long-term use (beyond two weeks of treatment). No differences in pain or spasm scores were noted among these agents, nor when compared to benzodiazepines.[18] However, nonbenzodiazepine (including cyclobenzaprine) treatment was found to have a lower risk of medication abuse and continuation of use against medical advice. Side effects such as sedation and ataxia are also less pronounced with nonbenzodiazepine antispasmodics.

In a study on the treatment of musculoskeletal pain treatment with cyclobenzaprine alone or in combination with ibuprofen, no significant differences in pain scores were noted among the three treatment groups. Peak benefit was found to occur on day 7 of the treatment for all groups.[19]


Cyclobenzaprine 10mg

By mouth, cyclobenzaprine is marketed as Apo-Cyclobenzaprin, Fexmid and Novo-Cycloprine. Flexeril was discontinued.[20] It is available in generic form. A once-a-day, extended-release formulation, Amrix, is available.[21] Cyclobenzaprine is also used by compounding pharmacies in topical creams.

Cyclobenzaprine is regulated in the U.S. for prescription use only. Though it does not fall within most governmental guidelines as a controlled substance, possession of it without a valid or current prescription may be illegal, depending upon various state and local laws.[citation needed]


A rapidly absorbed form of cyclobenzaprine is being studied in the treatment for post-traumatic stress disorder. [22]


  1. ^ Micromedex® 2010 – DRUGDEX® Evaluations (Cyclobenzaprine Hydrochloride)
  2. ^ "Cyclobenzaprine Hydrochloride Tablets USP Revised: April 2005 Rx only". 
  3. ^ a b c d e f g "Flexeril (Cyclobenzaprine HCl) Tablets" (pdf). U. S. Food and Drug Administration. 2003. Retrieved 26 July 2009 
  4. ^ a b c Chou R, Peterson K, Helfand M (2004). "Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review". Journal of Pain Symptom Management. 28 (2): 140–175. doi:10.1016/j.jpainsymman.2004.05.002. PMID 15276195. 
  5. ^ "Cyclobenzaprine Hydrochloride" (subscription required). MicroMedex. 5 Feb 2010. Retrieved 16 Feb 2010. 
  6. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 2. ISBN 9781284057560. 
  7. ^ van Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM (2003). Van Tulder, Maurits W, ed. "Muscle relaxants for non-specific low back pain". Cochrane Database Systematic Reviews. 2 (1–2): 91–9. doi:10.1002/14651858.CD004252. PMID 12804507. 
  8. ^ a b Browning R; Jackson JL; O’Malley PG (2001). "Cyclobenzaprine and back pain: a meta-analysis". Archives of Internal Medicine. 161 (13): 1613–1620. doi:10.1001/archinte.161.13.1613. PMID 11434793. 
  9. ^ a b c "Cyclobenzaprine official FDA information, side effects, and uses". October 2009. Retrieved 19 Feb 2010. 
  10. ^ Ashby P, Burke D, Rao S, et al. (1972). "Assessment of cyclobenzaprine in the treatment of spasticity". J Neurol Neurosurg Psychiatry. 35 (5): 599–605. doi:10.1136/jnnp.35.5.599. PMC 494138free to read. PMID 4563483. 
  11. ^ Tofferi JK, Jackson JL, O'Malley PG (15 Feb 2004). "Treatment of fibromyalgia with cyclobenzaprine: A meta-analysis". Arthritis Rheum. 51 (1): 9–13. doi:10.1002/art.20076. PMID 14872449. 
  12. ^ Canadian Agency for Drugs and Technologies in Health; 2015 Feb 23. Long-term Use of Cyclobenzaprine for Pain: A Review of the Clinical Effectiveness. PMID 25763449
  13. ^ Potentially inappropriate medications for the elderly according to the revised Beers criteria. 2012. Duke Clinical Research Institute website.
  14. ^ "Flexeril: Side effects". Retrieved 22 Feb 2010. 
  15. ^ "High risk medications" (pdf). National Committee for Quality Assurance. Retrieved 22 Feb 2010. 
  16. ^ Chabria, Shiven B (17 July 2006). "Rhabdomyolysis: a manifestation of cyclobenzaprine toxicity". Journal of Occupational Medicine and Toxicology. 1 (1): 16. doi:10.1186/1745-6673-1-16. PMC 1540431free to read. PMID 16846511. Archived from the original on October 21, 2006. 
  17. ^ Keegan MT; Brown DR; Rabinstein AA (2006). "Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs". Anesthesia & Analgesia. 103 (6): 1466–8. doi:10.1213/01.ane.0000247699.81580.eb. PMID 17122225. 
  18. ^ "Medscape: Medscape Access". 
  19. ^ Childers, M.K.; Petri, M.; Laudadio, C.; Harrison, D.; Silber, S.; Bowen, D. (2004). "Comparison of cyclobenzaprine alone versus cyclobenzaprine plus ibuprofen in patients with acute musculoskeletal spasm and pain". Annals of Emergency Medicine. 44 (4): S87. doi:10.1016/j.annemergmed.2004.07.286. 
  20. ^ "Cyclobenzaprine Hydrochloride (cyclobenzaprine hydrochloride) - Drug Summary". Retrieved 28 April 2016. 
  21. ^ "Patient Web site for AMRIX® (Cyclobenzaprine Hydrochloride Extended‐Release Capsules)". 
  22. ^ "TNX-102 SL for Post-Traumatic Stress Disorder :: Tonix Pharmaceuticals Holding Corp. (TNXP)". Retrieved 2016-06-28.