cyclobenzaprine hydrochloride
Flexeril

Available forms
Available by prescription only
Tablets: 10 mg

Indications and dosages
 Adjunct in acute, painful musculoskeletal conditions. Adults: 20 to 40 mg P.O. divided b.i.d. to q.i.d.; maximum dose is 60 mg daily. Drug shouldn’t be administered for longer than 2 to 3 weeks.
 Fibrositis. Adults: 10 to 40 mg P.O. daily.

Pharmacodynamics
Skeletal muscle relaxant action: Cyclobenzaprine relaxes skeletal muscles through an unknown mechanism of action. Cyclobenzaprine is a CNS depressant.
 Drug also potentiates the effects of norepinephrine and exhibits anticholinergic effects similar to those of tricyclic antidepressants, including central and peripheral antimuscarinic actions, sedation, and an increase in heart rate.

Pharmacokinetics
Absorption: Almost completely absorbed during first pass through GI tract.
Distribution: About 93% is plasma protein-bound.
Metabolism: During first pass through GI tract and liver, drug and metabolites undergo enterohepatic recycling. The half-life of cyclobenzaprine is 1 to 3 days.
Excretion: Excreted primarily in urine as conjugated metabolites; also excreted in feces via bile as unchanged drug.

Contraindications and precautions
Contraindicated in patients who have received MAO inhibitors within 14 days; patients in acute recovery phase of MI; and patients with hyperthyroidism, hypersensitivity to drug, heart block, arrhythmias, conduction disturbances, or heart failure. Use cautiously in geriatric or debilitated patients and in those with increased intraocular pressure, glaucoma, or urine retention.

Interactions
Drug-drug. Antidyskinetics, antimuscarinics: Potentiates antimuscarinic effects. Use together cautiously.
CNS depressants: May potentiate CNS depression. Avoid use together.
Guanadrel, guanethidine: Decreases or blocks antihypertensive effects. Avoid use together.
MAO inhibitors: Hyperpyretic crisis, seizures, and death have occurred with concomitant administration of MAO inhibitors and tricyclics; potential for this interaction with cyclobenzaprine also exists. Allow 14 days to elapse after stopping MAO inhibitor therapy before starting cyclobenzaprine, and allow 5 to 7 days after stopping cyclobenzaprine therapy before starting MAO inhibitor.
Drug-lifestyle. Alcohol use: May potentiate CNS-depressant effects. Discourage alcohol use.

Adverse reactions
CNS: drowsiness, headache, insomnia, fatigue, asthenia, nervousness, confusion, dizziness.
EENT: blurred vision.
GI: dyspepsia, abnormal taste, constipation, nausea, dry mouth.

Effects on lab test results
None reported.

Overdose and treatment
Signs and symptoms of overdose include severe drowsiness, troubled breathing, syncope, seizures, tachycardia, arrhythmias, hallucinations, changes in body temperature, and vomiting.
 To treat overdose, induce emesis or perform gastric lavage. Give 20 to 30 g activated charcoal every 4 to 6 hours for 24 to 48 hours. Take ECG and monitor cardiac functions for arrhythmias. Monitor vital signs, especially body temperature and ECG. Maintain adequate airway and fluid intake. If needed, 1 to 3 mg I.V. physostigmine may be given to combat severe life-threatening antimuscarinic effects. Provide supportive therapy for arrhythmias, cardiac failure, circulatory shock, seizures, and metabolic acidosis as needed.

Special considerations
• Drug may cause effects and adverse reactions similar to those of other tricyclic antidepressants.
• Antimuscarinic effect of drug may inhibit salivary flow, resulting in development of dental caries, periodontal disease, oral candidiasis, and mouth discomfort.
• Drug is intended for short-term (2 or 3 weeks) treatment because risks and potential benefits with prolonged use aren’t known. Additionally, muscle spasm accompanying acute musculoskeletal conditions is usually transient.
• Spasmolytic effect usually begins within 1 or 2 days and may be manifested by lessening of pain and tenderness and an increase in range of motion and ability to perform activities of daily living.
Pediatric patients
• Drug isn’t recommended for children younger than age 15.
Geriatric patients
• Elderly patients are more sensitive to the effects of drug.

Patient education
• Warn patient about possible drowsiness and dizziness. Tell him to avoid hazardous activities that require alertness until reaction to drug is known.
• Advise patient to relieve dry mouth (anticholinergic effect) with frequent clear water rinses, extra fluid intake, or with sugarless gum or candy.
• Tell patient to report discomfort immediately.
• Advise patient to use cough and cold preparations cautiously because some products contain alcohol.
• Instruct patient to check with dentist to minimize risk of dental disease (tooth decay, fungal infections, or gum disease) if treatment lasts longer than 2 weeks.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use