Common side effects include headache, feeling tired, dizziness, and dry mouth.[5] Serious side effects may include an irregular heartbeat.[5] There is no evidence of harm in pregnancy, but it has not been well studied in this population.[5] It must not be used with an MAO inhibitor.[5] How it works is unclear.[5]
Cyclobenzaprine was approved for medical use in the United States in 1977.[5] It is available by prescription as a generic medication.[5] In 2021, it was the 45th most commonly prescribed medication in the United States, with more than 15million prescriptions.[6][7] It was not available in the United Kingdom as of 2012.[8]
Medical use
Cyclobenzaprine is used, in conjunction with physical therapy, to treat muscle spasms that occur because of acute musculoskeletal conditions.[9] After sustaining an injury, muscle spasms occur to stabilize the affected body part, which may increase pain to prevent further damage. Cyclobenzaprine is used to treat such muscle spasms associated with acute, painful musculoskeletal conditions.[10] It decreases pain in the first two weeks,[11][12] peaking in the first few days, but has no proven benefit after two weeks.[11][13] Since no benefit is proven beyond that, therapy should not be continued long-term.[10] It is the best-studied muscle relaxer.[11] It is not useful for spasticity due to neurologic conditions such as cerebral palsy.[10][14]
A 2004 review found benefit for fibromyalgia symptoms, with a reported number needed to treat of 4.8 (meaning that 1 person out of every 4.8 benefits from treatment) for pain reduction, but no change in fatigue or tender points.[15] A 2009 Cochrane review found insufficient evidence to justify its use in myofascial pain syndrome.[16] It may also be used along with other treatments for tetanus.[17]
Agitation is a common side effect observed, especially in the elderly. Some experts[who?] believe that cyclobenzaprine should be avoided in elderly patients because it can cause confusion, delirium, and cognitive impairment.[19][20] 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.[21]
Monoamine oxidase inhibitors taken within two weeks of cyclobenzaprine may result in serious, life-threatening side effects.[10]
Cyclobenzaprine may affect the medications used in surgical sedation and some surgeons request that patients temporarily discontinue its use prior to surgery.[25]
Pharmacology
Cyclobenzaprine is a centrally acting muscle relaxant.[26] Cyclobenzaprine is a 5-HT2 receptor antagonist; it relieves muscle spasm through action on the central nervous system at the brain stem, rather than targeting the peripheral nervous system or muscles themselves.[27]
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.
Pharmacokinetics
Cyclobenzaprine has an oral bioavailability of about 55% and approximately 93% is bound to proteins in plasma. The half-life of the drug is 18 hours and it has a plasma clearance of 0.7 litres per minute.[26][29][30]
Comparison to other medications
Cyclobenzaprine has been found to be not inferior to tizanidine, orphenadrine, and carisoprodol in the treatment of acute lower back pain, although none have 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.[31] However, nonbenzodiazepine (including cyclobenzaprine) treatment was found to have a lower risk of medication abuse and continuation of use against medical advice.[medical citation needed] Side effects such as sedation and ataxia are also less pronounced with nonbenzodiazepine antispasmodics.[medical citation needed]
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 seven of the treatment for all groups.[32]
Formulations
Cyclobenzaprine 10mg tablets
By mouth, cyclobenzaprine is marketed as Apo-Cyclobenzaprin, Fexmid, Flexeril and Novo-Cycloprine. It is available in generic form. A once-a-day, extended-release formulation, Amrix, is available.[33] Cyclobenzaprine is also used by compounding pharmacies in topical creams.[citation needed]
^Yang YW, Macdonald JB, Nelson SA, Sekulic A (December 2017). "Treatment of vismodegib-associated muscle cramps with cyclobenzaprine: A retrospective review". Journal of the American Academy of Dermatology. 77 (6): 1170–1172. doi:10.1016/j.jaad.2016.12.017. PMID29132849. S2CID8265576.
^"Long-term Use of Cyclobenzaprine for Pain: A Review of the Clinical Effectiveness". CADTH Rapid Response Reports. Ottawa, Ontario: Canadian Agency for Drugs and Technologies in Health. 23 February 2015. PMID25763449.
^Kobayashi H, Hasegawa Y, Ono H (September 1996). "Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending serotonergic systems". European Journal of Pharmacology. 311 (1): 29–35. doi:10.1016/0014-2999(96)00402-5. PMID8884233.
^Winchell GA, King JD, Chavez-Eng CM, Constanzer ML, Korn SH (January 2002). "Cyclobenzaprine pharmacokinetics, including the effects of age, gender, and hepatic insufficiency". Journal of Clinical Pharmacology. 42 (1): 61–9. doi:10.1177/0091270002042001007. PMID11808825. S2CID7749001.
