CLINICAL PHARMACOLOGY
Cyclobenzaprine HCl relieves skeletal muscle spasm of
local origin without interfering with muscle function.
It is ineffective in muscle spasm due to central nervous
system disease.
Cyclobenzaprine reduced or abolished skeletal muscle
hyperactivity in several animal models. Animal studies
indicate that cyclobenzaprine does not act at the neuromuscular
junction or directly on skeletal muscle. Such studies
wshow that cyclobenzaprine acts primarily within the central
nervous system at brain stem as opposed to spinal cord
levels, although its action on the latter may contribute
to its overall skeletal muscle relaxant activity. Evidence
suggests that the net effect of cyclobenzaprine is a reduction
of tonic somatic motor activity, influencing both gamma
(g) and alpha (a) motor systems.
Pharmacological studies in animals showed a similarity
between the effects of cyclobenzaprine and the structurally
related tricyclic antidepressants, including reserpine
antagonism, norepinephrine potentiation, potent peripheral
and central anticholinergic effects, and sedation. Cyclobenzaprine
caused slight to moderate increase in heart rate in animals.
Cyclobenzaprine is well absorbed after oral administration,
but there is a large intersubject variation in plasma
levels. Cyclobenzaprine is eliminated quite slowly with
a half-life as long as one to three days. It is highly
bound to plasma proteins, is extensively metabolized primarily
to glucuronide-like conjugates, and is excreted primarily
via the kidneys.
No significant effect on plasma levels or bioavailability
of cyclobenzaprine HCl or aspirin was noted when single
or multiple doses of the two drugs were administered concomitantly.
Concomitant administration of cyclobenzaprine HCl and
aspirin is usually well tolerated and no unexpected or
serious clinical or laboratory adverse effects have been
observed. No studies have been performed to indicate whether
cyclobenzaprine HCl enhances the clinical effect of aspirin
or other analgesics, or whether analgesics enhance the
clinical effect of cyclobenzaprine HCl in acute musculoskeletal
conditions.
CLINICAL STUDIES
Controlled clinical studies wshow that cyclobenzaprine
HCl significantly improves the signs and symptoms of skeletal
muscle spasm as compared with placebo. The clinical responses
include improvement in muscle spasm as determined by palpation,
reduction in local pain and tenderness, increased range
of motion, and less restriction in activities of daily
living. When daily observations were made, clinical improvement
was observed as early as the first day of therapy.
Eight double-blind controlled clinical studies were performed
in 642 patients comparing cyclobenzaprine HCl, diazepam,
and placebo. Muscle spasm, local pain and tenderness,
limitation of motion, and restriction in activities of
daily living were evaluated. In three of these studies
there was a significantly greater improvement with cyclobenzaprine
HCl than with diazepam, while in the other studies the
improvement following both treatments was comparable.
Although the frequency and severity of adverse reactions
observed in patients treated with cyclobenzaprine HCl
were comparable to those observed in patients treated
with diazepam, dry mouth was observed more frequently
in patients treated with cyclobenzaprine HCl and dizziness
more frequently in those treated with diazepam. The incidence
of drowsiness, the most frequent adverse reaction, was
similar with both drugs.
Analysis of the data from controlled studies shows that
cyclobenzaprine HCl produces clinical improvement whether
or not sedation occurs.
Surveillance Program: A post-marketing
surveillance program was carried out in 7607 patients with
acute musculoskeletal disorders, and included 297 patients
treated for 30 days or longer. The overall effectiveness
of cyclobenzaprine HCl was similar to that observed in the
double-blind controlled studies; the overall incidence of
adverse effects was less (see ADVERSE REACTIONS).
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