|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Medication Safety Issues
Sound-alike/look-alike issues:
Cyclobenzaprine may be confused with cycloSERINE, cyproheptadine
Flexeril® may be confused with Floxin®
Pronunciation
(sye kloe BEN za preen)
U.S. Brand Names
Index Terms
Generic Available
Yes: Excludes capsule
Canadian Brand Names
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)
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; do not use concomitantly or within 14 days of MAO inhibitors; hyperthyroidism; congestive heart failure, arrhythmias, heart block; acute recovery phase of MI
Warnings/Precautions
Concerns related to adverse effects:
• 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).
• Toxic potential similar to tricyclic antidepressants: 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:
• Glaucoma: Use with caution in patients with angle-closure glaucoma or increased intraocular pressure.
• 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).
• Urinary hesitancy/retention: Use with caution in patients with urinary hesitancy or retention.
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: Use with caution in the elderly; plasma concentrations and incidence of adverse reactions are increased in the elderly compared to younger adults. Extended release capsules not recommended for use in elderly.
• Pediatrics: Safety and efficacy have not been established in patients <15 years of age.
Adverse Reactions
>10%:
Central nervous system: Drowsiness (29% to 39%), dizziness (1% to 11%)
Gastrointestinal: Xerostomia (6% to 32%)
1% to 10%:
Central nervous system: Fatigue (1% to 6%), confusion (1% to 3%), headache (1% to 3%), irritability (1% to 3%), mental acuity decreased (1% to 3%), nervousness (1% to 3%), somnolence (1% to 2%)
Gastrointestinal: Abdominal pain (1% to 3%), constipation (1% to 3%), diarrhea (1% to 3%), dyspepsia (?4%), 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% (Limited to important or life-threatening): Ageusia, agitation, anaphylaxis, angioedema, anorexia, anxiety, arrhythmia, ataxia, cholestasis, depression, diaphoresis, diplopia, disorientation, dysarthria, facial edema, flatulence, gastritis, hallucinations, hepatitis (rare), hypertonia, hypotension, insomnia, jaundice, liver function tests abnormal, malaise, muscle twitching, palpitation, paresthesia, pruritus, psychosis, rash, seizure, syncope, tachycardia, thirst, tinnitus, tongue edema, tremor, urinary retention, urticaria, vasodilation, vertigo, vomiting
Metabolism/Transport Effects
Substrate of CYP1A2 (major), 2D6 (minor), 3A4 (minor)
Drug Interactions
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: Paliperidone. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. 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
MAO Inhibitors: Cyclobenzaprine may enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce dosage of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
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
Ethanol/Nutrition/Herb Interactions
Food: Food increases bioavailability (peak plasma concentrations increased by 35% and area under the curve by 20%) of the extended release capsule.
Ethanol: Avoid ethanol (may increase CNS depression).
Herb/Nutraceutical: Avoid valerian, kava kava, gotu kola (may increase CNS depression).
Storage
Amrix®, Flexeril®: Store at room temperature of 15°C to 30°C (59°F to 86°F).
Fexmid®: Store at room temperature of 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
Onset of action: Immediate release tablet: ?1 hour
Duration: Immediate release tablet: 12-24 hours
Absorption: Complete
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 hours
Time to peak, serum: Immediate release tablet: 3-8 hours; Extended release capsule: 7-8 hours
Excretion: Urine (as inactive metabolites); feces (as unchanged drug)
Dosage
Oral: 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 to 7.5-10 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.
Patient Education
Take exactly as directed. Do not increase dose or discontinue this medication without consulting prescriber. Do not use alcohol, prescriptive or OTC antidepressants, sedatives, or pain medications without consulting prescriber. You may experience drowsiness, dizziness, lightheadedness (avoid driving or engaging in tasks that require alertness until response to drug is known); or urinary retention (void before taking medication). Report excessive drowsiness or mental agitation, chest pain, skin rash, swelling of mouth/face, difficulty speaking, ringing in ears, or blurred vision. Breast-feeding precaution: Breast-feeding is not recommended.
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.
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
Assess effectiveness and interactions of other medications patient may be taking. Monitor effectiveness of therapy (according to rationale for therapy) and adverse reactions at beginning and periodically during therapy. Assess knowledge/teach patient appropriate use, interventions to reduce side effects (postural hypotension precautions), and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release, as hydrochloride:
Amrix®: 15 mg, 30 mg
Tablet, 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): $515.98
Tablets (Cyclobenzaprine HCl)
5 mg (30): $13.99
10 mg (30): $13.99
Tablets (Flexeril)
5 mg (30): $55.99
10 mg (30): $58.99
References
Ambre JJ, “Cyclobenzaprine Overdose,” Ann Intern Med, 1985, 102(4):559-60.
Heckerling PS, Bartow TJ, “Paradoxical Diaphoresis in Cyclobenzaprine Poisoning,” Ann Intern Med, 1984, 101(6):881.
Linden CH, Mitchiner JC, Lindzon RD, et al, “Cyclobenzaprine Overdosage,” J Toxicol Clin Toxicol, 1983, 20(3):281-8.
Spiller HA, Winter ML, Mann KV, et al, “Five Year Multicenter Retrospective Review of Cyclobenzaprine Toxicity,” Vet Hum Toxicol, 1994, 36:370.
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.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
|
