FLEXERIL
Flexeril is a muscle relaxant used to treat muscle spasms. We now carry the generic equivalent to Flexeril, which is cyclobenzaprine.
Flexeril is a common drug for patients with frequent, recurrent back spasms. Neurologists and rheumatologists - doctors that often wind up with chronic back pain patients - often prescribe this drug since it satisfies the urge to treat back pain with medications other than pain pills. The way Flexeril works is not completely known. The chemical structure of the drug is almost identical to the structure of common antidepressants known to doctors as tricyclics.
Brand Name(s): Flexeril
Generic Name Cyclobenzaprine
Phonetic: (sye kloe ben' za preen)
Who is this for?
Cyclobenzaprine, a muscle relaxant, is used with rest, physical therapy, and
other measures to relax muscles and relieve pain and discomfort caused by
strains, sprains, and other muscle injuries. This medication is sometimes
prescribed for other uses; ask your doctor or pharmacist for more information.
How does it work?
Cyclobenzaprine works on nerves in the spinal cord to dull nerve impulses or
signals to the muscles. Dulling these nerve impulses will help relieve muscle
spasms.
When should I be careful taking it?
Before taking cyclobenzaprine,
tell your doctor and pharmacist if you are allergic to cyclobenzaprine or any
other drugs.
tell your doctor and pharmacist what prescription and nonprescription drugs you
are taking or have taken within the last 2 weeks, especially medications for
depression, seizures, allergies, coughs, or colds; MAO inhibitors [phenelzine (Nardil),
tranylcypromine (Parnate)]; sedatives; sleeping pills; tranquilizers; and
vitamins.
tell your doctor if you have an overactive thyroid gland, heart disease,
glaucoma, or difficulty urinating.
tell your doctor if you are pregnant, plan to become pregnant, or are
breast-feeding. If you become pregnant while taking cyclobenzaprine, call your
doctor immediately.
you should know that this drug may make you drowsy. Do not drive a car or
operate machinery until you know how cyclobenzaprine affects you.
remember that alcohol can add to the drowsiness caused by this drug.
What side effects should I watch for?
Although side effects from cyclobenzaprine are not common, they can occur. Tell
your doctor if any of these symptoms are severe or do not go away:
drowsiness
dry mouth
dizziness
upset stomach
If you experience any of the following symptoms, call your doctor immediately:
severe skin rash
swelling of the face or tongue
difficulty breathing or swallowing
irregular heart rate
chest pain
fever
seizures
How should I take it?
Cyclobenzaprine comes as a tablet to take by mouth. It usually is taken two to
four times a day. Do not take this drug for more than 3 weeks without talking to
your doctor. Follow the directions on your prescription label carefully, and ask
your doctor or pharmacist to explain any part you do not understand. Take
cyclobenzaprine exactly as directed. Do not take more or less of it or take it
more often than prescribed by your doctor.
What happens if I miss a dose?
Take the missed dose as soon as you remember it. However, if it is almost time
for the next dose, skip the missed dose and continue your regular dosing
schedule. Do not take a double dose to make up for the missed one.
Where should I keep it?
Keep this medication in the container it came in, tightly closed, and out of
reach of children. Store it at room temperature and away from excess heat and
moisture (not in the bathroom). Throw away any medication that is outdated or no
longer needed. Talk to your pharmacist about the proper disposal of your
medication.
Flexeril / Cyclobenzaprine
Patient Monograph
CATEGORIES: Muscle spasm; Pain, musculoskeletal; Pregnancy Category B; FDA
Approved 1977 Aug; Top 200 Drugs
Drug Classes: Musculoskeletal agents; Relaxants, skeletal muscle
BRAND NAMES: Flexeril
FOREIGN BRAND AVAILABILITY:
Cyben (Korea)
Flexiban (Italy; Portugal)
Tensodox (Peru)
Yurelax (Spain)
COST OF THERAPY:
$31.25 (Musculoskeletal Pain; Flexeril; 10 mg; 3 tablets/day; 10 day supply)
$10.20 (Musculoskeletal Pain; Generic tablets; 10 mg; 3 tablets/day; 10 day
supply)
DESCRIPTION
Cyclobenzaprine hydrochloride is a white, crystalline tricyclic amine salt with
the empirical formula C20H21N·HCl and a molecular weight of 311.9. It has a
melting point of 217°C, and a pKa of 8.47 at 25°C. It is freely soluble in water
and alcohol, sparingly soluble in isopropanol, and insoluble in hydrocarbon
solvents. If aqueous solutions are made alkaline, the free base separates.
Cyclobenzaprine hydrochloride is designated chemically as 3-(5H-dibenzo[a,
d]cyclohepten-5-ylidene)-N, N-dimethyl-1-propanamine hydrochloride.
Cyclobenzaprine hydrochloride is supplied as 10 mg tablets for oral
administration. Inactive Ingredients: Hydroxypropyl cellulose, hydroxypropyl
methylcellulose, iron oxide, lactose, magnesium stearate, starch, and titanium
dioxide.
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 (CNS).
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 show that
cyclobenzaprine acts primarily within the CNS 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 1-3 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 2 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 show 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 3 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 postmarketing 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).
INDICATIONS AND USAGE
Cyclobenzaprine HCl is indicated as an adjunct to rest and physical therapy for
relief of muscle spasm associated with acute, painful musculoskeletal
conditions.
Improvement is manifested by relief of muscle spasm and its associated signs and
symptoms, namely, pain, tenderness, limitation of motion, and restriction in
activities of daily living.
Cyclobenzaprine HCl should be used only for short periods (up to 2 or 3 weeks)
because adequate evidence of effectiveness for more prolonged use is not
available and because muscle spasm associated with acute, painful
musculoskeletal conditions is generally of short duration and specific therapy
for longer periods is seldom warranted.
Cyclobenzaprine HCl has not been found effective in the treatment of spasticity
associated with cerebral or spinal cord disease, or in children with cerebral
palsy.
CONTRAINDICATIONS
Hypersensitivity to the drug.
Concomitant use of monoamine oxidase inhibitors or within 14 days after their
discontinuation.
Acute recovery phase of myocardial infarction, and patients with arrhythmias,
heart block or conduction disturbances, or congestive heart failure.
Hyperthyroidism.
WARNINGS
Cyclobenzaprine is closely related to the tricyclic antidepressants, e.g.,
amitriptyline and imipramine. In short-term studies for indications other than
muscle spasm associated with acute musculoskeletal conditions, and usually at
doses somewhat greater than those recommended for skeletal muscle spasm, some of
the more serious CNS reactions noted with the tricyclic antidepressants have
occurred (see ADVERSE REACTIONS).
Cyclobenzaprine HCl may interact with monoamine oxidase (MAO) inhibitors.
Hyperpyretic crisis, severe convulsions, and deaths have occurred in patients
receiving tricyclic antidepressants and MAO inhibitor drugs.
Tricyclic antidepressants have been reported to produce arrhythmias, sinus
tachycardia, prolongation of the conduction time leading to myocardial
infarction, and stroke.
Cyclobenzaprine HCl may enhance the effects of alcohol, barbiturates, and other
CNS depressants.
PRECAUTIONS
General
Because of its atropine-like action, cyclobenzaprine HCl should be used with
caution in patients with a history of urinary retention, angle-closure glaucoma,
increased intraocular pressure, and in patients taking anticholinergic
medication.
Information for the Patient
Cyclobenzaprine HCl may impair mental and/or physical abilities required for
performance of hazardous tasks, such as operating machinery or driving a motor
vehicle.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
In rats treated with cyclobenzaprine HCl for up to 67 weeks at doses of
approximately 5-40 times the maximum recommended human dose, pale, sometimes
enlarged, livers were noted and there was a dose-related hepatocyte vacuolation
with lipidosis. In the higher dose groups this microscopic change was seen after
26 weeks and even earlier in rats which died prior to 26 weeks; at lower doses,
the change was not seen until after 26 weeks.
Cyclobenzaprine did not affect the onset, incidence or distribution of neoplasia
in an 81-week study in the mouse or in a 105 week study in the rat.
At oral doses of up to 10 times the human dose, cyclobenzaprine did not
adversely affect the reproductive performance or fertility of male or female
rats. Cyclobenzaprine did not demonstrate mutagenic activity in the male mouse
at dose levels of up to 20 times the human dose.
Pregnancy Category B
Reproduction studies have been performed in rats, mice, and rabbits at doses up
to 20 times the human dose, and have revealed no evidence of impaired fertility
or harm to the fetus due to cyclobenzaprine HCl. There are, however, no adequate
and well-controlled studies in pregnant women. Because animal reproduction
studies are not always predictive of human response, this drug should be used
during pregnancy only if clearly needed.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because
cyclobenzaprine is closely related to the tricyclic antidepressants, some of
which are known to be excreted in human milk, caution should be exercised when
cyclobenzaprine HCl is administered to a nursing woman.
Pediatric Use
Safety and effectiveness of cyclobenzaprine HCl in pediatric patients below 15
years of age have not been established.
DRUG-INTERACTIONS
Cyclobenzaprine HCl may enhance the effects of alcohol, barbiturates, and other
CNS depressants.
Tricyclic antidepressants may block the antihypertensive action of guanethidine
and similarly acting compounds.
ADVERSE REACTIONS
The following list of adverse reactions is based on the experience in 473
patients treated with cyclobenzaprine HCl in controlled clinical studies, 7607
patients in the postmarketing surveillance program, and reports received since
the drug was marketed. The overall incidence of adverse reactions among patients
in the surveillance program was less than the incidence in the controlled
clinical studies.
The adverse reactions reported most frequently with cyclobenzaprine HCl were
drowsiness, dry mouth, and dizziness. The incidence of these common adverse
reactions was lower in the surveillance program than in the controlled clinical
studies (see TABLE 1).
TABLE 1
Clinical Studies Surveillance Program
Drowsiness 39% 16%
Dry mouth 27% 7%
Dizziness 11% 3%
Among the less frequent adverse reactions, there was no appreciable difference
in incidence in controlled clinical studies or in the surveillance program.
Adverse reactions which were reported in 1-3% of the patients were:
fatigue/tiredness, asthenia, nausea, constipation, dyspepsia, unpleasant taste,
blurred vision, headache, nervousness, and confusion.
The following adverse reactions have been reported at an incidence of less than
1 in 100:
Body as a Whole: Syncope, malaise.
Cardiovascular: Tachycardia, arrhythmia, vasodilatation, palpitation,
hypotension.
Digestive: Vomiting, anorexia, diarrhea, gastrointestinal pain, gastritis,
thirst, flatulence, edema of the tongue, abnormal liver function and rare
reports of hepatitis, jaundice, and cholestasis.
Hypersensitivity: Anaphylaxis, angioedema, pruritus, facial edema, urticaria,
rash.
Musculoskeletal: Local weakness.
Nervous System and Psychiatric: Ataxia, vertigo, dysarthria, tremors, hypertonia,
convulsions, muscle twitching, disorientation, insomnia, depressed mood,
abnormal sensations, anxiety, agitation, abnormal thinking and dreaming,
hallucinations, excitement, paresthesia, diplopia.
Skin: Sweating.
Special Senses: Ageusia, tinnitus.
Urogenital: Urinary frequency and/or retention.
Other reactions, reported rarely for cyclobenzaprine HCl under circumstances
where a causal relationship could not be established or reported for other
tricyclic drugs, are listed to serve as alerting information to physicians:
Body as a Whole: Chest pain, edema.
Cardiovascular: Hypertension, myocardial infarction, heart block, stroke.
Digestive: Paralytic ileus, tongue discoloration, stomatitis, parotid swelling.
Endocrine: Inappropriate ADH syndrome.
Hematic and Lymphatic: Purpura, bone marrow depression, leukopenia, eosinophilia,
thrombocytopenia.
Metabolic, Nutritional, and Immune: Elevation and lowering of blood sugar
levels, weight gain or loss.
Musculoskeletal: Myalgia.
Nervous System and Psychiatric: Decreased or increased libido, abnormal gait,
delusions, peripheral neuropathy, Bell's palsy, alteration in EEG patterns,
extrapyramidal symptoms.
Respiratory: Dyspnea.
Skin: Photosensitization, alopecia.
Urogenital: Impaired urination, dilatation of urinary tract, impotence,
testicular swelling, gynecomastia, breast enlargement, galactorrhea.
DRUG ABUSE AND DEPENDENCE
Pharmacologic similarities among the tricyclic drugs require that certain
withdrawal symptoms be considered when cyclobenzaprine HCl is administered, even
though they have not been reported to occur with this drug. Abrupt cessation of
treatment after prolonged administration may produce nausea, headache, and
malaise. These are not indicative of addiction.
OVERDOSAGE
Manifestations
High doses may cause temporary confusion, disturbed concentration, transient
visual hallucinations, agitation, hyperactive reflexes, muscle rigidity,
vomiting, or hyperpyrexia, in addition to anything listed under ADVERSE
REACTIONS. Based on the known pharmacologic actions of the drug, overdosage may
cause drowsiness, hypothermia, tachycardia and other cardiac rhythm
abnormalities such as bundle branch block, ECG evidence of impaired conduction,
and congestive heart failure. Other manifestations may be dilated pupils,
convulsions, severe hypotension, stupor, and coma.
The acute oral LD50 of cyclobenzaprine HCl is approximately 338 and 425 mg/kg in
mice and rats, respectively.
Treatment
Treatment is symptomatic and supportive. Empty the stomach as quickly as
possible by emesis, followed by gastric lavage. After gastric lavage, activated
charcoal may be administered. Twenty (20) to 30 g of activated charcoal may be
given every 4-6 hours during the first 24-48 hours after ingestion. An ECG
should be taken and close monitoring of cardiac function must be instituted if
there is any evidence of dysrhythmia. Maintenance of an open airway, adequate
fluid intake, and regulation of body temperature are necessary.
The intravenous administration of 1-3 mg of physostigmine salicylate is reported
to reverse symptoms of poisoning by atropine and other drugs with
anticholinergic activity. Physostigmine may be helpful in the treatment of
cyclobenzaprine overdose. Because physostigmine is rapidly metabolized, the
dosage of physostigmine should be repeated as required, particularly if
life-threatening signs such as arrhythmias, convulsions, and deep coma recur or
persist after the initial dosage of physostigmine. Because physostigmine itself
may be toxic, it is not recommended for routine use.
Standard medical measures should be used to manage circulatory shock and
metabolic acidosis. Cardiac arrhythmias may be treated with neostigmine,
pyridostigmine, or propranolol. When signs of cardiac failure occur, the use of
a short-acting digitalis preparation should be considered. Close monitoring of
cardiac function for not less than 5 days is advisable.
Anticonvulsants may be given to control seizures.
Dialysis is probably of no value because of low plasma concentrations of the
drug.
Since overdosage is often deliberate, patients may attempt suicide by other
means during the recovery phase. Deaths by deliberate or accidental overdosage
have occurred with this class of drugs.
DOSAGE AND ADMINISTRATION
The usual dosage of cyclobenzaprine HCl is 10 mg 3 times a day, with a range of
20-40 mg a day in divided doses. Dosage should not exceed 60 mg a day. Use of
cyclobenzaprine HCl for periods longer than 2 or 3 weeks is not recommended (see
INDICATIONS AND USAGE).
HOW SUPPLIED
Cyclobenzaprine HCl tablets are D-shaped, film coated tablets. 10 mg Tablets:
Butterscotch yellow colored, with code "156" one side and "WPPh" on the other.