Class: Centrally Acting Skeletal Muscle Relaxants
VA Class: MS200
Chemical Name: 3-(5H-dibenzo[a,d]cyclohepten-5-ylidine)-N,N-dimethyl-1-propanamine hydrochloride
Molecular Formula: C20H21N·HCl
CAS Number: 6202-23-9
Brands: Flexeril
Introduction
Centrally acting skeletal muscle relaxant; structurally and pharmacologically related to tricyclic antidepressants.101
Uses for Cyclobenzaprine
Muscular Conditions
Adjunct to rest and physical therapy for the relief of muscular spasm associated with acute, painful musculoskeletal conditions.101
For low back pain, generally reserve skeletal muscle relaxants for adjunctive treatment when pain is unresponsive to OTC analgesics (e.g., NSAIAs).104 105 106 107 108 109
Skeletal muscle relaxants less well tolerated than NSAIAs, and clinical superiority to NSAIAs not established for low back pain.104 105 106 107 108 109
Various skeletal muscle relaxants appear to have comparable efficacy for low back pain relief101 104 and are more effective than placebo.104 106 108
Initially, symptomatic control of acute low back pain focuses on providing sufficient comfort to allow maximum possible activity while awaiting spontaneous recovery; later, as aid to overcome specific activity intolerance.108
Because of rapid spontaneous recovery rate, efficacy of various therapies may be difficult to establish;108 improvement of low back pain usually occurs within 2 weeks, substantial improvement within 4 weeks.107
Insufficient evidence to indicate whether cyclobenzaprine enhances the effects of aspirin or other analgesics, or vice versa, in the management of painful musculoskeletal conditions.101
Ineffective for the treatment of cerebral or spinal disease-associated spasticity or in children with cerebral palsy.101
Cyclobenzaprine Dosage and Administration
Administration
Administer orally.101
Dosage
Available as cyclobenzaprine hydrochloride; dosage expressed in terms of the salt.101
Pediatric Patients
Muscular Conditions
Oral
Adolescents ≥15 years of age: 5 mg 3 times daily; may increase dosage to 10 mg 3 times daily depending on response.101
Adults
Muscular Conditions
Oral
5 mg 3 times daily; may increase dosage to 10 mg 3 times daily depending on response.101
Prescribing Limits
Pediatric Patients
Muscular Conditions
Oral
Do not administer for more than 2–3 weeks.101
Adults
Muscular Conditions
Oral
Do not administer for more than 2–3 weeks.101
Special Populations
Hepatic Impairment
Initiate with caution in patients with mild hepatic impairment.101 Consider less frequent dosing; start with 5-mg dose and increase slowly.101
Use not recommended in patients with moderate or severe hepatic impairment.101
Geriatric Patients
Consider less frequent dosing; start with 5-mg dose and increase slowly.101
Cautions for Cyclobenzaprine
Contraindications
Known hypersensitivity to cyclobenzaprine or any ingredient in the formulation.101
Concomitant or recent (within 14 days) therapy with MAO inhibitor.101
Acute recovery phase of MI.101
Arrhythmias, heart block or conduction disorders, or CHF.101
Hyperthyroidism.101
Warnings/Precautions
Warnings
Similarity to Tricyclic Antidepressants
Shares the toxic potentials of tricyclic antidepressants; observe the usual precautions associated with tricyclic antidepressant therapy.101 a
Cardiac Effects
Arrhythmias, sinus tachycardia, prolongation of the conduction time leading to MI, and stroke reported with tricyclic antidepressants.101
CNS Effects
May cause serious CNS effects, especially when recommended dosage is exceeded.101
Performance of activities requiring mental alertness or physical coordination may be impaired.101
Concurrent use of other CNS depressants may potentiate CNS depression.101 (See Interactions: Specific Drugs.)
General Precautions
Anticholinergic Effects
Potential for adverse anticholinergic effects.101 Use with caution in patients with history of urinary retention, angle-closure glaucoma, or increased intraocular pressure or in patients receiving anticholinergic drugs.101
Specific Populations
Pregnancy
Category B.101 a
Lactation
Not known whether cyclobenzaprine is distributed into milk; however, distribution into milk is likely, since other tricyclic drugs distribute into milk.101 b Use with caution.101 a b
Pediatric Use
Safety and efficacy not established in children <15 years of age.101
Geriatric Use
Increased plasma concentrations.101
Increased frequency and severity of adverse effects (with or without concomitant drug therapy).101 Increased risk of adverse CNS effects (e.g., hallucinations, confusion, sedation), adverse cardiovascular effects resulting in falls or other sequelae, and interactions with other drugs or diseases.101
Use only if clearly needed.101 Cautious dosing recommended.101 (See Geriatric Patients under Dosage and Administration.)
Hepatic Impairment
Increased plasma concentrations and susceptibility to sedation.101
Initiate with caution in patients with mild hepatic impairment.101 (See Hepatic Impairment under Dosage and Administration.)
Use not recommended in patients with moderate or severe hepatic impairment.101
Common Adverse Effects
Drowsiness, dry mouth, dizziness, fatigue, headache.101
Interactions for Cyclobenzaprine
Metabolized by CYP3A4, 1A2, and (to a lesser extent) 2D6.101
Shares the drug interaction potential of tricyclic antidepressants; consider the usual interactions of tricyclic antidepressant therapy.101
Specific Drugs
Drug | Interaction | Comments |
|---|---|---|
Aspirin | No substantial change in plasma concentrations or bioavailability of either drug.101 | |
CNS depressants (e.g., alcohol, barbiturates) | Additive effects.101 | |
Hypotensive agents (e.g., guanethidine) | May block uptake and antihypertensive effects of guanethidine and other similarly acting drugs.101 | |
MAO inhibitors | Possible hyperpyretic crisis, seizures, and death.101 | Cyclobenzaprine contraindicated in patients currently or recently (within 14 days) receiving MAO inhibitor.101 |
Naproxen | Possible increased risk of drowsiness.101 | |
Tramadol | Increased risk of seizures.101 |
Cyclobenzaprine Pharmacokinetics
Absorption
Bioavailability
Well absorbed following oral administration110 111 but appears to undergo first-pass metabolism;112 113 115 mean oral bioavailability is 33–55%.101 110 111 113 114 Undergoes enterohepatic circulation.101 110 113
Special Populations
In patients ≥65 years of age, mean steady-state AUC is about 1.7 times greater than AUC in younger adults.101
In patients with mild to moderate hepatic impairment, peak plasma concentration and AUC are twice the values in healthy individuals.101 110
Distribution
Extent
Widely distributed into most body tissues.110
Plasma Protein Binding
About 93%.101 111
Elimination
Metabolism
Extensively metabolized in the liver via oxidation and conjugation.101 110 112 113 115 Oxidative N-demethylation mediated by CYP3A4, 1A2, and (to a lesser extent) 2D6.101 110
Elimination Route
Eliminated mainly in urine as inactive glucuronide metabolites; <1% eliminated as unchanged drug.101 110 112 113
Half-life
About 18 hours (range: 8–37 hours).101 110
Stability
Storage
Oral
Tablets
25°C (may be exposed to 15–30°C).101
ActionsActions
CNS depressant with sedative and skeletal muscle relaxant effects.101 a
Precise mechanism of action not known.101 a Does not directly relax skeletal muscle and, unlike neuromuscular blocking agents, does not depress neuronal conduction, neuromuscular transmission, or muscle excitability.101 a
Like tricyclic antidepressants, potentiates the effects of norepinephrine and has anticholinergic effects.101 a
Advice to Patients
Potential for drug to impair mental alertness and physical coordination, particularly when used with alcohol or other CNS depressants.101 Use caution when driving or operating machinery.101
Potential for more frequent or severe adverse effects in geriatric patients.101
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.101 a b
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.101 a b
Importance of informing patients of other important precautionary information.101 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 5 mg | Flexeril | McNeil |
10 mg* | Flexeril | McNeil |
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Cyclobenzaprine HCl 10MG Tablets (CADISTA): 30/$13.99 or 60/$16.98
Cyclobenzaprine HCl 5MG Tablets (CADISTA): 30/$13.99 or 60/$16.98
Fexmid 7.5MG Tablets (VICTORY PHARMA): 30/$135.99 or 90/$365.97
Flexeril 10MG Tablets (MCNEIL CONSUMER): 30/$66.48 or 90/$176.6
Flexeril 5MG Tablets (MCNEIL CONSUMER): 30/$60.44 or 90/$168.38
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
Only references cited for selected revisions after 1984 are available electronically.
100. Gatter RA. Pharmacotherapeutics in fibrositis. Am J Med. 1986; 81(Suppl 3A):63-6. [IDIS 222657] [PubMed 3464210]
101. McNeil. Cyclobenzaprine hydrochloride (Flexeril) tablets prescribing information. Fort Washington, PA: 2003 Feb.
102. Liebelt EL, Francis PD. Cyclic Antidepressants. In: Goldfrank’s Toxicologic Emergencies. 7th Ed. 2002. McGraw-Hill New York, NY.
103. Borenstein DG, Korn S. Efficacy of a low-dose regimen of cyclobenzaprine acute skeletal muscle spasm: results of two placebo-controlled trials. Clin Ther. 2003; 25:1056-73. [IDIS 497263] [PubMed 12809957]
104. van Tulder MW, Touray T, Furlan AD et al. Muscle relaxants for non-specific low back pain. The Cochrane Library. From their web site (). Accessed 11/10/2003.
105. van Tulder MW, Scholten RJPM, Kowes BW, et al. Non-steroidal anti-inflammatory drugs for low back pain. The Cochrane Library. From their web site (). Accessed 11/10/2003.
106. Department of Veterans Affairs Veterans Health Administration Office of Quality & Performance. Management of Person with Low Back Pain/Sciatica in Primary Care. From the web site (). Accessed 8/25/2003.
107. Agency for Healthcare Research and Quality. Adult low back pain. From the National Guideline Clearinghouse website. (). Accessed 8/25/2003.
108. U.S. Department of Health and Human Services. Public Health Service. Agency for Halath Care Policy and Research. Acute low back problems in adults. Clinical Practice Guideline.1994; No. 14
109. U.S. Department of Health and Human Services. Public Health Service. Agency for Health Care Policy and Research. Acute low back problems in adults: Assessment and treatment. Clinical Practice Guideline. Quick Reference Guide for Clinicians.1994; No. 14
110. Winchell GA, King JD, Chavez-Eng CM et al. Cyclobenzaprine pharmacokinetics, including the effects of age, gender, and hepatic insufficiency. J Clin Pharmacol. 2002;42:61-9. IDIS 475544
111. Hucker HB, Stauffer SC, Balletto AJ et al. Physiological disposition and metabolism of cyclobenzaprine in the rat, dog, rhesus monkey, and man. Drug Metab Dispos. 1978; 6:659-72. [IDIS 118762] [PubMed 33029]
112. Hucker HB, Stauffer SC, Albert KS et al. Plasma levels and bioavailability of cyclobenzaprine in human subjects. J Clin Pharmacol. 1977; Nov-Dec:719-27.
113. Till AE, Constanzer ML, Demetriades J et al. Evidence for route dependent biotransformation of cyclobenzaprine hydrochloride. Biopharm Drug Dispos. 1982; 3:19-28. [IDIS 147637] [PubMed 7082776]
114. Nugent LW, Irvin JD, Till AE et al. Cyclobenzaprine hydrochloride: Pharmacokinetics and bioavailability following oral and intramuscular administration. J Clin Pharmacol. 1982; 22(Suppl): 12A.
115. Hucker HB, Stauffer SC. GLC determination of cyclobenzaprine in plasma and urine. J Pharm Sci. 1976; 65:1253-5. [IDIS 70381] [PubMed 978450]
a. AHFS Drug Information 2003. McEvoy GK, ed. Cyclobenzaprine hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2004:1330-2.
b. AHFS Drug Information 2003. McEvoy GK, ed. Tricyclic antidepressants general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2004:2234-41.
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