|Trade names||Amrix, Flexeril|
|Bioavailability||33% to 55%|
|Metabolism||major: CYP3A4, CYP1A2; minor: CYP2D6, N-demethylation|
|Biological half-life||32 hours (range 8–37 hours; n=18)|
|Chemical and physical data|
|Molar mass||275.387 g/mol|
|3D model (JSmol)|
Cyclobenzaprine, sold under the brand name Flexeril among others, is a muscle relaxer medication used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions. It is the best-studied drug for this application. It has also been used off-label for fibromyalgia treatment.
After sustaining an injury, painful muscle spasms may occur to stabilize the affected body part and prevent further damage. Cyclobenzaprine is used to treat such muscle spasms associated with acute, painful musculoskeletal conditions. It decreases pain in the first two weeks, peaking in the first few days, but has no proven benefit after two weeks. Since no benefit is proven beyond that, therapy should not be continued long-term. It is not useful for spasticity due to neurologic conditions such as cerebral palsy.
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). It may also be used along with other treatments for tetanus.
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. Drowsiness and dry mouth appear to intensify with increasing dose. Dysphagia, a life threatening side-effect, may rarely occur.
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. Treatment protocols and support should follow the same as for any structurally related tricyclic, such as tricyclic antidepressants.
The most common effects of overdose are drowsiness and tachycardia. Rare but potentially critical complications are cardiac arrest, abnormal heart rhythms, severe low blood pressure, seizures, and neuroleptic malignant syndrome. Life-threatening overdose is rare, however, as the median lethal dose is about 338 milligrams/kilogram in mice and 425 mg/kg in rats. The potential harm is increased when central nervous system depressants and antidepressants are also used; deliberate overdose often includes alcohol among other drugs.
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.
These substances may interact with cyclobenzaprine:
- Central nervous system depressants (e.g. alcohol, opioids, benzodiazepines, nonbenzodiazepines, phenothiazines, carbamates, barbiturates, major tranquilizers)
- Monoamine oxidase inhibitors taken within two weeks of cyclobenzaprine may result in serious, life-threatening side effects.
Cyclobenzaprine may affect the medications used in surgical sedation and some surgeons request that patients temporarily discontinue its use prior to surgery. The prescribing physician should be consulted prior to discontinuing, and resuming, cyclobenzaprine.
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 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. 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 seven of the treatment for all groups.
By mouth, cyclobenzaprine is marketed as Apo-Cyclobenzaprin, Fexmid and Novo-Cycloprine. Flexeril was discontinued. It is available in generic form. A once-a-day, extended-release formulation, Amrix, is available. 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.
A rapidly absorbed form of cyclobenzaprine is being studied in the treatment for post-traumatic stress disorder.
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