Skeletal Muscle Relaxant
Action And Clinical Pharmacology: Cyclobenzaprine relieves skeletal muscle spasm of local origin without interfering with muscle function. It is ineffective in muscle spasm due to CNS disease.
Controlled clinical studies show that cyclobenzaprine improves the signs and the symptoms of skeletal muscle spasm.
Pharmacokinetics: Cyclobenzaprine is well absorbed in man. After oral or i.v. doses (10 mg) of 4-labeled cyclobenzaprine to human subjects, plasma levels of radioactivity were comparable. In addition, the excretion of radioactivity was similar after both routes (38 to 51% in the urine; 14 to 15% in the feces), suggesting that oral absorption is almost complete. The half-life varies from 1 to 3 days. No effect on plasma levels or bioavailability was noted in 14 human subjects, when cyclobenzaprine and multiple doses of ASA was coadministered.
Cyclobenzaprine is extensively metabolized in man. In the study with 4-labeled drug, about 4% of the dose was excreted in the urine as unchanged cyclobenzaprine. The metabolites (probably glucuronides) were excreted as water-soluble conjugates. After oral or i.v. administration of 40 mg of unlabeled cyclobenzaprine to 2 subjects, only 0.2 to 1.5% of the dose was excreted as unchanged drug in the urine within 24 hours.
Indications And Clinical Uses: An adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions.
Cyclobenzaprine 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 has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy.
Contra-Indications: Hypersensitivity to cyclobenzaprine. Concomitant use of MAO 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.
Manufacturers’ Warnings In Clinical States: Use of cyclobenzaprine for periods longer than 2 or 3 weeks is not recommended (see Indications).
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 tricyclic antidepressants have occurred (see Warnings below and Adverse Effects).
Cyclobenzaprine may interact with MAO inhibitors. Hyperpyretic crises, severe convulsions and deaths have occurred in patients receiving tricyclic antidepressants and MAO inhibitors.
Tricyclic antidepressants have been reported to produce arrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke.
Cyclobenzaprine may enhance the effects of alcohol, barbiturates, and other CNS depressants.
Precautions: Occupational Hazards: Cyclobenzaprine may impair the mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle.
Because of its atropine-like action, cyclobenzaprine 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.
Tricyclic antidepressants may block the antihypertensive action of guanethidine and similarly acting compounds.
Pregnancy: The safe use of cyclobenzaprine in pregnant women has not been established. Therefore, it should not be administered to women of childbearing potential unless, in the opinion of the treating physician, the anticipated benefits outweigh the possible hazards to the fetus.
Lactation: Because it is likely that cyclobenzaprine is excreted in milk, it should not be given to nursing mothers.
Children: Safety and effectiveness of cyclobenzaprine in children below the age of 15 have not been established.
Adverse Reactions: The following adverse reactions have been reported with cyclobenzaprine.
Most frequent: drowsiness (40%), dry mouth (28%), dizziness (11%).
Less frequent: increased heart rate (and several cases of tachycardia), weakness, fatigue, dyspepsia, nausea, paresthesia, unpleasant taste, blurred vision, insomnia, convulsions and abnormal liver function: hepatitis, jaundice and cholestasis.
Rare: sweating, myalgia, dyspnea, abdominal pain, constipation, coated tongue, tremors, dysarthria, euphoria, nervousness, disorientation, confusion, headache, urinary retention, decreased bladder tonus, ataxia, depressed mood, hallucinations and allergic reactions including rash, urticaria and edema of the face and tongue.
The listing which follows includes other adverse reactions which have been reported with tricyclic compounds, but not with cyclobenzaprine when used in short term studies in muscle spasm of peripheral origin. Some of these reactions were noted, however, when cyclobenzaprine was studied for other indications, usually in higher dosage. Pharmacologic similarities among the tricyclic drugs require that each of the reactions be considered when cyclobenzaprine is administered.
Cardiovascular: hypotension, hypertension, palpitation, myocardial infarction, arrhythmias, heart block, stroke.
CNS and Neuromuscular: confusional states, disturbed concentration, delusions, excitement, anxiety, restlessness, nightmares, numbness and tingling of the extremities, peripheral neuropathy, incoordination, seizures, alteration in EEG patterns, extrapyramidal symptoms, tinnitus, syndrome of inappropriate ADH (antidiuretic hormone) secretion.
Anticholinergic: disturbance of accommodation, paralytic ileus, dilatation of urinary tract.
Hematologic: bone marrow depression including agranulocytosis, leukopenia, eosinophilia, purpura, thrombocytopenia.
Gastrointestinal: epigastric distress, vomiting, anorexia, stomatitis, diarrhea, parotid swelling, black tongue.
Endocrine: testicular swelling and gynecomastia in the male, breast enlargement and galactorrhea in the female. Increased or decreased libido, elevation and lowering of blood sugar levels.
Other: weight gain or loss, urinary frequency, mydriasis, alopecia.
Withdrawal Symptoms: Abrupt cessation of treatment after prolonged administration may produce nausea, headache and malaise. These are not indicative of addiction.
Symptoms And Treatment Of Overdose: Symptoms: 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 Effects. Based on 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.
Treatment: 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 to 30 g of the activated charcoal may be given every 4 to 6 hours during the first 24 to 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 slow i.v. administration of 1 to 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, its dosage should be repeated as often as required when life-threatening signs such as arrhythmias, convulsions, and deep coma recur or persist.
Use standard medical measures 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: 10 mg 3 times/day, with a range of 20 to 40 mg/day in divided doses. Dosage should not exceed 60 mg/day. Use of cyclobenzaprine is not indicated or recommended for periods longer than 2 or 3 weeks.
Availability And Storage: Each butterscotch yellow, film-coated, D-shaped tablet, coded 931, contains: cyclobenzaprine HCl 10 mg. Also contains lactose. Gluten- and tartrazine-free. Bottles of 100 and 500. (Shown in Product Recognition Section)
FLEXERIL® Frosst Cyclobenzaprine HCl Skeletal Muscle Relaxant
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