Cyclobenzaprine, brand names Amrix, Flexeril and Fexmid, 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. A new bedtime formulation of cyclobenzaprine is under development for the management of
fibromyalgia syndrome.
Medical use 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. 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 patient reporting pain reduction.
In elderly patients, cyclobenzaprine HCl may be started at a lower dose and titrated slowly
upward. Cyclobenzaprine is recommended for use up to 3 weeks, but clinical efficacy has
not been demonstrated beyond this point and long term use of cyclobenzaprine is not recommended.
Cyclobenzaprine, however, has not been documented to cause intense physical and psychological
withdrawal symptoms following discontinuation such as those which occur with its benzodiazepine,
barbiturate, and carbamate alternatives, although the potential for rebound plasticity is of
clinical relevance. Side effects
Meta-analysis studies have found significantly increased rates of drowsiness, dry mouth,
dizziness, and adverse events of any kind in patients taking cyclobenzaprine versus
placebo. Drowsiness and dry mouth appear to intensify with increasing dose.
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 NCQA recommends avoiding the use of cyclobenzaprine in the
elderly because of the potential for more severe side effects. There is one case report
of overdose causing rhabdomyolysis. Treatment protocols and support should follow the same
as for any structurally related tricyclic, such as tricyclic antidepressants.
Overdose The most common effects of overdose are drowsiness
and tachycardia. Rare but potentially critical complications are cardiac arrest, cardiac
dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome. Life-threatening
overdose is rare, however, as the median lethal dose is approximately 338 mg/kg 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. Interactions
Cyclobenzaprine has major contraindications with monoamine oxidase inhibitors. At least
one study also found increased risk of serotonin syndrome when cyclobenzaprine was taken with
the serotonergic drugs duloxetine or phenelzine. The following substances may interact with
cyclobenzaprine: Alcohol
Central nervous system depressants Tricyclic antidepressants may increase the
chance of side effects. Monoamine oxidase inhibitors taken within
two weeks of cyclobenzaprine may result in serious, life-threatening side effects.
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 Cyclobenzaprine has been found to be non-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. No differences in pain
or spasm scores were noted among these agents, nor when compared to benzodiazepines. However,
nonbenzodiazepine 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.
Synthesis Cyclobenzaprine, N,N-dimethyl-3-(dibenzo[a,d]cyclohepten-5-ylidene)propylamine,
is synthesized by reacting 5H-dibenzo[a,d]cyclohepten-5-one with 3-dimethylaminopropylmagnesium chloride
and subsequent dehydration of the resulting carbinol in acidic conditions into cyclobenzaprine.
N.B. Cyclobenzaprine is made from Dibenzosuberenone starting material.
Formulations
Orally, cyclobenzaprine is marketed as Apo-Cyclobenzaprin, Flexeril, Fexmid and Novo-Cycloprine. 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.
See also Amitriptyline
Cyproheptadine References