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Pronunciation
(sye kloe BEN za preen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of muscle spasm associated with acute, painful musculoskeletal conditions
Use: Dental
Treatment of muscle spasm associated with acute temporomandibular joint pain (TMJ)
Use: Unlabeled
Treatment of muscle spasm associated with acute temporomandibular joint pain (TMJ)
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if clearly needed.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to cyclobenzaprine or any component of the formulation; during or within 14 days of MAO inhibitors; hyperthyroidism; congestive heart failure; arrhythmias; heart block or conduction disturbances; acute recovery phase of MI
Warnings/Precautions
Concerns related to adverse effects:
• Anticholinergic effects: Use with caution in patients with angle-closure glaucoma, increased intraocular pressure, or urinary frequency/hesitancy.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Toxicity: Cyclobenzaprine shares the toxic potentials of the tricyclic antidepressants, including prolongation of conduction time, arrhythmias, and tachycardia; the usual precautions of tricyclic antidepressant therapy should be observed.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with mild hepatic impairment; plasma concentrations increased twofold in presence of mild impairment. Not recommended in moderate-to-severe hepatic impairment. Extended release capsules not recommended in patients with hepatic impairment of any severity (mild, moderate, or severe).
Concurrent drug therapy issues:
• MAO inhibitors: Do not use concomitantly or within 14 days after MAO inhibitors; combination may cause hypertensive crisis and/or severe convulsions.
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Elderly: Muscle relaxants are poorly tolerated by the elderly due to potent anticholinergic effects, sedation, and risk of fracture. Efficacy is questionable at dosages tolerated by elderly patients; avoid use (Beers Criteria). Extended release capsules not recommended for use in elderly.
Adverse Reactions
>10%:
Central nervous system: Drowsiness (29% to 39%), dizziness (1% to 11%)
Gastrointestinal: Xerostomia (21% to 32%)
1% to 10%:
Central nervous system: Fatigue (1% to 6%), headache (1% to 5%), confusion (1% to 3%), irritability (1% to 3%), mental acuity decreased (1% to 3%), nervousness (1% to 3%), somnolence (1% to 2%)
Gastrointestinal: Dyspepsia (≤4%), abdominal pain (1% to 3%), constipation (1% to 3%), diarrhea (1% to 3%), gastric regurgitation (1% to 3%), nausea (1% to 3%), unpleasant taste (1% to 3%)
Neuromuscular & skeletal: Weakness (1% to 3%)
Ocular: Blurred vision (1% to 3%)
Respiratory: Pharyngitis (1% to 3%), upper respiratory infection (1% to 3%)
<1%, postmarketing, and/or case reports: Abnormal dreams, abnormal thoughts, ageusia, agitation, anaphylaxis, angioedema, anorexia, anxiety, arrhythmia, ataxia, cholestasis, depression, diaphoresis, diplopia, disorientation, dysarthria, excitement (paradoxical, children), facial edema, flatulence, gastritis, gastrointestinal pain, hallucinations, hepatitis (rare), hypertonia, hypotension, insomnia, jaundice, liver function tests abnormal, malaise, muscle twitching, palpitation, paresthesia, pruritus, psychosis, rash, seizures, syncope, tachycardia, thirst, tinnitus, tongue edema, tremor, urinary frequency, urinary retention, urticaria, vasodilation, vertigo, vomiting
Metabolism/Transport Effects
Substrate of CYP1A2 (major), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Levocabastine (Nasal); Paliperidone. Risk C: Monitor therapy
Antipsychotics: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MAO Inhibitors: Cyclobenzaprine may enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Risk C: Monitor therapy
Metyrosine: CNS Depressants may enhance the sedative effect of Metyrosine. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Food: Food increases bioavailability (peak plasma concentrations increased by 35% and area under the curve by 20%) of the extended release capsule.
Herb/Nutraceutical: Avoid valerian, kava kava, gotu kola (may increase CNS depression).
Storage
Amrix®, Flexeril®: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Fexmid®: Store at 20°C to 25°C (68°F to 77°F).
Mechanism of Action
Centrally-acting skeletal muscle relaxant pharmacologically related to tricyclic antidepressants; reduces tonic somatic motor activity influencing both alpha and gamma motor neurons
Pharmacodynamics/Kinetics
Metabolism: Hepatic via CYP3A4, 1A2, and 2D6; may undergo enterohepatic recirculation
Bioavailability: 33% to 55%
Half-life elimination: Range: 8-37 hours; Immediate release tablet: 18 hours; Extended release capsule: 32-33 hours
Time to peak, serum: Extended release capsule: 7-8 hours
Excretion: Urine (as inactive metabolites); feces (as unchanged drug)
Dosage
Oral: Muscle spasm: Note: Do not use longer than 2-3 weeks
Capsule, extended release:
Adults: Usual: 15 mg once daily; some patients may require up to 30 mg once daily
Elderly: Use not recommended
Tablet, immediate release:
Children ≥15 years and Adults: Initial: 5 mg 3 times/day; may increase up to 10 mg 3 times/day if needed
Elderly: Initial: 5 mg; titrate dose slowly and consider less frequent dosing
Dosage adjustment in hepatic impairment:
Capsule, extended release: Mild-to-severe impairment: Use not recommended.
Tablet, immediate release:
Mild impairment: Initial: 5 mg; use with caution; titrate slowly and consider less frequent dosing
Moderate-to-severe impairment: Use not recommended
Dental Usual Dosing
Treatment of muscle spasm associated with acute TMJ pain (Note: Do not use longer than 2-3 weeks): Oral:
Adults: Initial: 5 mg 3 times/day; may increase to 7.5-10 mg 3 times/day if needed
Elderly: 5 mg 3 times/day; plasma concentration and incidence of adverse effects are increased in the elderly; dose should be titrated slowly
Administration: Oral
Extended release capsules: Administer at the same time each day. Do not crush or chew.
Test Interactions
May cause false-positive serum TCA screen.
Patient Education
Do not use alcohol. You may experience drowsiness, dizziness, lightheadedness, or urinary retention. Report excessive drowsiness or skin rash.
Geriatric Considerations
High doses in the elderly caused drowsiness and dizziness; therefore, use the lowest dose possible. Because cyclobenzaprine causes anticholinergic effects, it may not be the skeletal muscle relaxant of choice in the elderly.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria: Quality of evidence - moderate; Strength of recommendation - strong).
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness and dizziness are common; may cause nervousness or confusion
Mental Health: Effects on Psychiatric Treatment
Contraindicated with MAO inhibitors or within 14 days of MAO inhibitor; concurrent use with psychotropics may exacerbate the dry mouth and sedation commonly seen with cyclobenzaprine
Nursing: Physical Assessment/Monitoring
May cause significant CNS depression. Caution patients about sedation.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release, oral, as hydrochloride: 15 mg, 30 mg
Amrix®: 15 mg, 30 mg
Tablet, oral, as hydrochloride: 5 mg, 10 mg
Fexmid®: 7.5 mg
Flexeril®: 5 mg, 10 mg
Pricing: U.S. (www.drugstore.com)
Capsule, 24-hour (Amrix)
15 mg (60): $649.99
Capsule, 24-hour (Cyclobenzaprine HCl)
15 mg (30): $286.00
30 mg (30): $345.99
Tablets (Cyclobenzaprine HCl)
5 mg (30): $13.99
10 mg (30): $13.99
Tablets (Flexeril)
5 mg (30): $60.44
10 mg (30): $66.48
References
"American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults," J Am Geriatr Soc, 2012 [epub ahead of print].
Heckerling PS and Bartow TJ, “Paradoxical Diaphoresis in Cyclobenzaprine Poisoning,” Ann Intern Med, 1984, 101(6):881.
Theoharides TC, Harris RS, and Weckstein D, “Neuroleptic Malignant-Like Syndrome Due to Cyclobenzaprine?” J Clin Psychopharmacol, 1995, 15(1):79-81.
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(1):61-9.
Wong EC, Koenig J, and Turk J, “Potential Interference of Cyclobenzaprine and Norcyclobenzaprine With HPLC Measurement of Amitriptyline and Nortriptyline: Resolution by GC-MS Analysis,” J Anal Toxicol, 1995, 19(4):218-24.
International Brand Names
Lexi-Comp.com
Last full review/revision April 2012
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