VA Class:MS200
Cyclobenzaprine is a centrally acting skeletal muscle relaxant.1, 101
Cyclobenzaprine hydrochloride is used as an adjunct to rest and physical therapy for the relief of muscular spasm associated with acute, painful musculoskeletal conditions.1, 101
Evidence supporting the efficacy of skeletal muscle relaxants is generally low to moderate in quality; while these agents appear to be more effective than placebo in providing short-term relief of acute low back pain, they are associated with a high incidence of adverse effects (e.g., sedation).104, 106, 109, 209, 210, 211, 212 Although comparative studies are limited, available data suggest that various skeletal muscle relaxants generally have similar efficacy for such use.104, 106, 108, 109 Acute low back pain usually is a benign and self-limiting condition that improves spontaneously over time;105, 106, 108 therefore, nonpharmacologic treatment strategies (e.g., heat, massage) are recommended.209 If pharmacologic therapy is required, experts state that a nonsteroidal anti-inflammatory agent (NSAIA) or a skeletal muscle relaxant may be used; however, these drugs have been shown to result in only small improvements in pain relief and can increase the risk of adverse effects.104, 106, 107, 108, 209 In general, skeletal muscle relaxants should be used with caution after weighing the potential risks against the benefits in individual patients.104, 106, 107, 108 Although skeletal muscle relaxants are often used in combination with NSAIAs for the treatment of acute low back pain, randomized controlled studies generally have not demonstrated any additional improvement in pain or functional outcomes with such combination therapy compared with use of an NSAIA alone.210, 212, 213
Efficacy of cyclobenzaprine hydrochloride 10 mg immediate-release tablets was established in 8 controlled clinical studies comparing cyclobenzaprine, diazepam, and placebo for their effect on muscle spasm, local pain and tenderness, limitation of motion, and restriction in activities of daily living.1 Improvement in patients receiving cyclobenzaprine was substantially greater than in those receiving diazepam in 3 studies and was comparable to diazepam in the remaining 5 studies.1
Efficacy of cyclobenzaprine hydrochloride 5 mg immediate-release tablets was evaluated in 2 controlled clinical studies; in one study patients received cyclobenzaprine hydrochloride 5 or 10 mg or placebo 3 times daily, and in the second study patients received 2.5 or 5 mg of the drug or placebo 3 times daily.1, 103 In both studies, efficacy of cyclobenzaprine hydrochloride 5 mg was substantially greater than placebo for patient-assessed primary end points (i.e., global impression of change, medication helpfulness, and relief from starting backache) by the seventh day of treatment.1, 103 In addition, cyclobenzaprine 5 mg was substantially more effective than placebo for a physician-assessed secondary end point (reduction in presence and extent of palpable muscle spasm).1, 103 In the study comparing cyclobenzaprine 5 or 10 mg 3 times daily with placebo, both dosages of the drug were substantially more effective than placebo by the third or fourth day (48-72 hours after the first dose of medication) of treatment.1, 103 The only efficacy-related difference between the 2 dosages was in onset of patient-rated relief from starting backache, which occurred after the third or fourth dose in patients receiving 5 mg but after the first 2 doses in patients receiving 10 mg.103 In the second study, the 2.5-mg dosage of cyclobenzaprine hydrochloride was no more effective than placebo.103 A subanalysis of data from patients in both studies who received either cyclobenzaprine hydrochloride (5 mg 3 times daily as tablets) or placebo and did not report somnolence demonstrated a meaningful treatment effect for all primary efficacy variables for the 5-mg dose despite the absence of somnolence in these patients.103
Efficacy of cyclobenzaprine hydrochloride extended-release capsules was evaluated in 2 controlled clinical studies in patients with acute painful musculoskeletal conditions.101 Both dosages of cyclobenzaprine hydrochloride evaluated in these studies (15 and 30 mg once daily) were more effective than placebo for the primary efficacy end point (patient-rated medication helpfulness).101 In one of the studies, patients receiving the 30-mg once-daily dosage also experienced improvements in other patient-rated outcomes (relief from local pain due to muscle spasm, restriction of movement, and global impression of change).101 However, no substantial differences were observed between cyclobenzaprine and placebo for physician-rated global assessment, patient-rated restriction in activities of daily living, and quality of sleep.101
No well-controlled clinical studies have been performed to determine whether cyclobenzaprine will enhance the clinical effects of aspirin or other analgesics or vice versa when such combinations are used to manage acute musculoskeletal conditions.1 Analysis of data from controlled studies indicates that an effective dosage of cyclobenzaprine may produce clinical improvement whether or not sedation occurs.1, 103
Cyclobenzaprine is ineffective in the treatment of spasticity associated with cerebral or spinal disease or in children with cerebral palsy.1
Cyclobenzaprine is administered orally (as immediate-release tablets or extended-release capsules).1, 101
The extended-release capsules should be swallowed intact.101 Alternatively, the capsules may be opened and the contents sprinkled onto a tablespoon of applesauce and consumed immediately without chewing; foods other than applesauce have not been tested and should not be used.101 Following administration, patients should rinse their mouth to ensure that all the capsule contents have been swallowed.101 Any unused portion of the capsules should be discarded.101
Cyclobenzaprine should be used only for short periods (e.g., up to 2-3 weeks) because adequate evidence of effectiveness for more prolonged use is not available and because muscle spasm associated with acute, painful musculoskeletal conditions generally is of short duration and specific therapy for longer periods seldom is warranted.1, 101
The recommended dosage of cyclobenzaprine hydrochloride immediate-release tablets for most adults and adolescents 15 years of age and older is 5 mg 3 times daily.1 Depending on response, dosage may be increased to 10 mg 3 times daily.1
The usual adult dosage of cyclobenzaprine hydrochloride extended-release capsules is 15 mg once daily (administered at approximately the same time each day).101 Some patients may require a dosage of up to 30 mg once daily.101
The manufacturer of cyclobenzaprine hydrochloride tablets states that less frequent dosing should be considered in patients with mild hepatic impairment, beginning with a 5-mg dose and slowly titrating upward.1 Use of the drug is not recommended in patients with moderate or severe hepatic impairment.1
Because of limited dosing flexibility, the manufacturer of the extended-release capsules states that this dosage form is not recommended for use in patients with hepatic impairment.101
The manufacturer of cyclobenzaprine hydrochloride immediate-release tablets states that less frequent dosing should be considered in geriatric patients, initiating cyclobenzaprine hydrochloride with a 5-mg dose and titrating upward slowly.1
Cyclobenzaprine extended-release capsules are not recommended for use in geriatric patients.101
The most common adverse effects reported in patients receiving cyclobenzaprine in clinical studies were drowsiness, dry mouth, dizziness, fatigue, and headache.1 Cyclobenzaprine is closely related to the tricyclic antidepressants, and the possibility that cyclobenzaprine may cause adverse effects similar to those of the tricyclic antidepressants should be considered.1
Drowsiness1 occurred in 29 or 38% of patients receiving cyclobenzaprine 5 or 10 mg, respectively, compared with 10% of those receiving placebo in controlled studies; drowsiness also was reported in 39 or 16% of patients receiving cyclobenzaprine 10 mg in controlled studies or during postmarketing surveillance, respectively.1 Dizziness occurred in 1-3% of patients receiving cyclobenzaprine 5 or 10 mg in controlled studies, and in 11 or 3% of patients receiving cyclobenzaprine 10 mg in clinical studies or during postmarketing surveillance, respectively.1 Fatigue occurred in 6% of patients receiving either 5 or 10 mg of cyclobenzaprine compared with 3% of those receiving placebo in controlled studies; fatigue or tiredness occurred in 1-3% of patients receiving 10 mg of the drug in controlled studies and in postmarketing surveillance.1
Headache occurred in 5% of those receiving 5 or 10 mg of cyclobenzaprine and in 8% of those receiving placebo in controlled studies; headache occurred in 1-3% of patients receiving 10 mg of the drug in controlled studies and postmarketing surveillance.1 Irritability, decreased mental acuity, nervousness, asthenia, and confusion occurred in 1-3% of patients receiving 5 or 10 mg of cyclobenzaprine in controlled studies or during postmarketing surveillance in patients receiving 10 mg of the drug.1
Malaise, seizures, ataxia, vertigo, dysarthria, hypertonia, tremors, disorientation, insomnia, depressed mood, abnormal sensations, anxiety, agitation, psychosis, abnormal thinking, abnormal dreaming, hallucinations, excitement, paresthesia, and diplopia were reported during postmarketing surveillance or in less than 1% of patients receiving 10 mg of the drug in controlled studies.1 Other adverse nervous system effects that have been reported in patients receiving other tricyclic drugs or rarely with cyclobenzaprine but for which a causal relationship with the drug could not be established include decreased or increased libido, abnormal gait, delusions, aggressive behavior, paranoia, peripheral neuropathy, Bell's palsy, alterations in EEG patterns, and extrapyramidal manifestations.1
Dry mouth occurred in 21 or 32% of patients receiving 5 or 10 mg, respectively, of cyclobenzaprine and in 7% of those receiving placebo in controlled studies.1 Dry mouth also occurred in 27 or 7% of patients receiving 10 mg of the drug in clinical studies or during postmarketing surveillance, respectively.1 Abdominal pain, acid regurgitation, dyspepsia, constipation, diarrhea, nausea, and unpleasant taste occurred in 1-3% of patients receiving 5 or 10 mg of cyclobenzaprine in controlled studies or during postmarketing surveillance in patients receiving 10 mg of the drug.1 Vomiting, anorexia, GI pain, gastritis, thirst, edema of the tongue, and flatulence were reported during postmarketing surveillance or in less than 1% of patients receiving 10 mg of the drug in controlled studies.1 Paralytic ileus, tongue discoloration, stomatitis, and parotid swelling were reported in patients receiving other tricyclic drugs or rarely with cyclobenzaprine, but a causal relationship with cyclobenzaprine could not be established.1
Upper respiratory infection and pharyngitis occurred in 1-3% of patients receiving cyclobenzaprine 5 or 10 mg in controlled studies. Dyspnea was reported in patients receiving other tricyclic drugs or rarely with cyclobenzaprine, but a causal relationship with cyclobenzaprine could not be established. 1
Syncope, tachycardia, arrhythmia, vasodilation, palpitation, and hypotension were reported during postmarketing experience or in less than 1% of patients receiving cyclobenzaprine 10 mg in clinical studies; hypertension, myocardial infarction, heart block, and stroke have been reported in patients receiving other tricyclic drugs or rarely with cyclobenzaprine, but a causal relationship with cyclobenzaprine could not be established.1
Dermatologic and Sensitivity Reactions
Anaphylaxis, angioedema, pruritus, facial edema, urticaria, rash, and sweating occurred during postmarketing experience or in less than 1% of patients receiving cyclobenzaprine 10 mg in clinical studies; photosensitivity, and alopecia have been reported in patients receiving other tricyclic drugs or rarely with cyclobenzaprine, but a causal relationship with cyclobenzaprine could not be established.1
Local weakness and muscle twitching were reported during postmarketing experience or in less than 1% of patients receiving cyclobenzaprine 10 mg in clinical studies; myalgia was reported in patients receiving other tricyclic drugs or rarely with cyclobenzaprine, but a causal relationship with cyclobenzaprine could not be established.1
Urinary frequency and/or urinary retention were reported during postmarketing experience or in less than 1% of patients receiving cyclobenzaprine 10 mg in clinical studies; impaired urination, dilatation of the urinary tract, impotence, testicular swelling, gynecomastia, breast enlargement, and galactorrhea have been reported in patients receiving other tricyclic drugs or rarely with cyclobenzaprine, but a causal relationship with cyclobenzaprine could not be established.1
Purpura, bone marrow depression, leukopenia, eosinophilia, and thrombocytopenia have been reported in patients receiving other tricyclic drugs or rarely with cyclobenzaprine, but a causal relationship with cyclobenzaprine could not be established.1
Abnormal liver function and rarely, hepatitis, jaundice, and cholestasis were reported during postmarketing experience or in less than 1% of patients receiving cyclobenzaprine 10 mg in clinical studies.1
Blurred vision was reported in 1-3% of patients receiving cyclobenzaprine 10 mg in controlled studies or in postmarketing surveillance. Tinnitus and ageusia each have been reported during postmarketing surveillance or in less than 1% of patients receiving cyclobenzaprine 10 mg in controlled studies.1
Elevation or reduction of blood glucose, weight gain or loss, syndrome of inappropriate antidiuretic hormone (SIADH), chest pain, and edema have been reported in patients receiving other tricyclic drugs or rarely with cyclobenzaprine, but a causal relationship with cyclobenzaprine could not be established.1
Precautions and Contraindications
Cyclobenzaprine shares the toxic and drug interaction potentials of the tricyclic antidepressants, and the usual precautions of tricyclic antidepressant therapy should be observed. (See Cautions and see Drug Interactions in the Tricyclic Antidepressants General Statement 28:16.04.28.) The possibility that cyclobenzaprine may cause other adverse effects similar to those of the tricyclic antidepressants should be kept in mind, especially when the dosage for musculoskeletal conditions is exceeded.
Cyclobenzaprine immediate-release tablets should be used with caution in patients with mild hepatic impairment, and should not be used in patients with moderate or severe hepatic impairment.1 Use of the extended-release capsule formulation is not recommended in any patient with hepatic impairment.101 Plasma concentrations of cyclobenzaprine are increased in patients with hepatic impairment, and such patients generally are more susceptible to sedation caused by the drug.1 (See Dosage and Administration: Dosage in Hepatic Impairment.)
Because cyclobenzaprine has anticholinergic effects, it should be used with caution in patients with a history of urinary retention, angle-closure glaucoma, or increased intraocular pressure or in patients receiving anticholinergic drugs.1 Patients should be warned that cyclobenzaprine may impair their ability to perform hazardous activities requiring mental alertness or physical coordination such as operating machinery or driving a motor vehicle, particularly when the drug is used with alcohol or other CNS depressants.1
Serotonin syndrome has occurred in patients receiving cyclobenzaprine in combination with serotonergic drugs.1 (See Drug Interactions: Serotonergic Drugs.) Serotonin syndrome is characterized by mental status and behavioral changes (e.g., agitation, confusion, hallucinations), altered muscle tone or neuromuscular activity (e.g., tremor, ataxia, hyperreflexia, clonus, rigidity), autonomic instability (e.g., diaphoresis, tachycardia, labile blood pressure, hyperthermia), and GI symptoms (e.g., nausea, vomiting, diarrhea).1 Patients should be advised of the symptoms of serotonin syndrome and instructed to seek immediate medical care if they develop any such symptoms.1 Cyclobenzaprine and any concomitant serotonergic agents should be discontinued immediately if serotonin syndrome is suspected and supportive treatment should be initiated.1
Cyclobenzaprine is contraindicated in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block or conduction disorders, known hypersensitivity to the drug or any ingredient in the formulation, and in the acute recovery phase following myocardial infarction.1, 101 Cyclobenzaprine also is contraindicated in patients receiving monoamine oxidase inhibitors and should not be used within 14 days following discontinuance of these agents.1, 101
Safety and efficacy of cyclobenzaprine immediate-release tablets in children and adolescents younger than 15 years of age have not been established.1
Safety and efficacy of cyclobenzaprine extended-release capsules have not been established in pediatric patients.101
Plasma concentrations of cyclobenzaprine and the frequency and severity of adverse effects, with or without other concomitantly used drugs, are increased in the elderly.1 Geriatric patients receiving cyclobenzaprine may be at increased risk for adverse CNS effects (e.g., hallucinations, confusion, sedation), adverse cardiovascular effects resulting in falls or other sequelae, and interactions with other drugs or diseases.1 Because of the risk of injury, skeletal muscle relaxants should generally be avoided in geriatric patients.111 If cyclobenzaprine is used in a geriatric patient, reduced dosages should be used.1 (See Dosage and Administration: Dosage in Geriatric Patients.)
Pregnancy, Fertility, and Lactation
Reproduction studies in animals using cyclobenzaprine doses up to 20 times the human dose have not revealed evidence of harm to the fetus. There are no adequate and controlled studies to date using cyclobenzaprine in pregnant women, and the drug should be used during pregnancy only when clearly needed.1
Reproduction studies in animals receiving cyclobenzaprine have not revealed evidence of impaired fertility.
It is not known whether cyclobenzaprine is distributed into milk;1 however, the drug is distributed into milk in rats.111 Because some related tricyclic antidepressants are distributed into milk, cyclobenzaprine should be used with caution in nursing women.1
Cyclobenzaprine is structurally and pharmacologically related to tricyclic antidepressants and shares the drug interaction potentials of these drugs.1 For additional information on potential drug interactions of tricyclic antidepressants, see Drug Interactions in the Tricyclic Antidepressants General Statement 28:16.04.28.
Concomitant use of cyclobenzaprine and monoamine oxidase (MAO) inhibitors has resulted in hyperpyretic crisis, seizures, and death.1 Cyclobenzaprine is contraindicated in patients receiving MAO inhibitors and should not be used within 14 days following discontinuance of these drugs.1 (See Drug Interactions: Serotonergic Drugs.)
Cyclobenzaprine may be additive with or may potentiate the action of other CNS depressants (e.g., alcohol, barbiturates).1 Cyclobenzaprine, especially when used concomitantly with alcohol or other CNS depressants, may impair the patient's ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).1
Concomitant use of cyclobenzaprine with serotonergic agents has been reported to cause serotonin syndrome.1 (See Cautions: Precautions and Contraindications.) Examples of serotonergic agents include selective serotonin-reuptake inhibitors (SSRIs), serotonin- and norepinephrine-reuptake inhibitors (SNRIs), tricyclic antidepressants, tramadol, meperidine, and MAO inhibitors.1
If concomitant use of cyclobenzaprine with a serotonergic agent is necessary, the patient should be carefully monitored, particularly during treatment initiation and dosage adjustments.1 Cyclobenzaprine and any concomitant serotonergic agents should be discontinued if serotonin syndrome is suspected.1
Cyclobenzaprine may enhance the risk of seizures in patients receiving tramadol.1
Nonsteroidal Anti-inflammatory Agents
Concomitant use of cyclobenzaprine with diflunisal or naproxen reportedly was well tolerated and did not appear to result in any unexpected adverse effects.1 However, concomitant use of cyclobenzaprine with naproxen has been associated with an increased incidence of drowsiness.1 Plasma concentrations of aspirin or cyclobenzaprine were unaffected when the drugs were administered concomitantly.1
Because the management of overdose is complex and changing, clinicians should consult a poison control center for additional information on the management of cyclobenzaprine overdosage.1 Cyclobenzaprine is structurally related to and shares the toxic potentials of the tricyclic antidepressants.1 For additional information about pathogenesis, manifestations, and treatment of toxic doses of structurally similar tricyclic antidepressants, see Acute Toxicity in the Tricyclic Antidepressants General Statement 28:16.04.28.
The manufacturer states that the acute oral LD50 of cyclobenzaprine is about 338 and 425 mg/kg in mice and rats, respectively.1
Manifestations of toxicity may develop rapidly after a cyclobenzaprine overdose, and rarely, death may occur.1 The most common toxic effects associated with cyclobenzaprine overdose are drowsiness and tachycardia; less frequent manifestations include tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations.1 Rarely, potentially serious effects may include cardiac arrest, chest pain, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome.1
Treatment of cyclobenzaprine overdosage, as in that of structurally similar tricyclic antidepressants, generally involves symptomatic and supportive care.1 Because of the potential for rapid clinical deterioration, cardiac function should be monitored, and IV access should be established; early endotracheal intubation and maintenance of an adequate airway are advised in patients with CNS depression and/or substantial ECG changes (e.g., wide-complex tachycardia).1
The manufacturer states that all patients suspected of an overdose with cyclobenzaprine should receive GI decontamination, including gastric lavage followed by activated charcoal; induction of emesis is contraindicated if consciousness is impaired.1, 102 However, the management of overdose is complex and changing, and clinicians should consult a poison control center for additional information on the management of cyclobenzaprine overdosage, particularly in pediatric patients.1 For additional information about specific treatment of cardiovascular and CNS disturbances associated with toxic doses of tricyclic compounds, including cyclobenzaprine, see Acute Toxicity: Treatment, in the Tricyclic Antidepressants General Statement 28:16.04.28.
Cyclobenzaprine is a CNS depressant that has sedative and skeletal muscle relaxant effects. The precise mechanism of action of the drug is not known. Cyclobenzaprine does not directly relax skeletal muscle and, unlike neuromuscular blocking agents, does not depress neuronal conduction, neuromuscular transmission, or muscle excitability.
Like the tricyclic antidepressants, cyclobenzaprine potentiates the effects of norepinephrine and has anticholinergic effects.
Orally administered cyclobenzaprine is well absorbed.110, 111 Cyclobenzaprine undergoes enterohepatic circulation,1, 110, 113 and appears to be metabolized during its first pass through the GI tract and/or liver.112, 113, 115 Mean oral bioavailability of the drug following administration of the immediate-release tablet formulation is estimated to range from 33-55%.1, 110, 113, 114 Following oral administration of a single 5- or 10-mg dose of cyclobenzaprine hydrochloride (as immediate-release tablets), peak plasma concentrations of 4.3 or 8.5 ng/mL, respectively, are attained in about 4 hours.110, 113, 114 When cyclobenzaprine is administered 3 times daily (as immediate-release tablets), steady-state plasma concentrations are attained within 3-4 days that are about fourfold greater than those after a single dose.1, 110 In healthy individuals receiving the drug 3 times daily (as immediate-release tablets), mean steady-state peak plasma cyclobenzaprine concentrations of 14.9 or 25.9 ng/mL were achieved at 4 or 3.9 hours after administration of a 5 or 10 mg dose, respectively.1, 110
Following administration of a single 15- or 30-mg dose of cyclobenzaprine hydrochloride (as the extended-release capsule formulation) in healthy adults, peak plasma concentrations of the drug were achieved in 7-8 hours.101 Administration of a single 30-mg capsule with food increased peak plasma concentrations by 35% and systemic exposure of the drug by 20%, but did not affect time to peak plasma concentration.101 Following multiple-dose administration (30 mg once daily for 7 days as extended-release capsules), accumulation of cyclobenzaprine was observed (2.5-fold increase in steady-state plasma concentrations).101
In a study evaluating the pharmacokinetics of cyclobenzaprine hydrochloride immediate-release tablets in geriatric individuals, values for steady-state mean area under the cyclobenzaprine concentration time curve (AUC) were about 1.7 times greater in individuals 65 years of age and older than in younger adults; mean AUCs in geriatric males were about 2.4 times greater than in younger males, and those in elderly females were about 1.2 times greater than in younger females.1 In geriatric patients older than 65 years of age receiving the extended-release capsules, AUC was increased by 40% and half-life of the drug was prolonged compared with younger adults.101 (See Cautions: Geriatric Precautions.)
Peak plasma concentrations and AUC of cyclobenzaprine (administered as immediate-release tablets) in 15 patients with mild hepatic impairment (and one with moderate hepatic impairment) were twice those observed in healthy individuals.1, 110 Insufficient data exist to establish the safety of cyclobenzaprine use in patients with moderate or severe hepatic impairment.1 (See Cautions: Precautions and Contraindications.)
Cyclobenzaprine is widely distributed into body tissues.110 It is not known if cyclobenzaprine is distributed into milk in humans;1 however, the drug is distributed into milk in rats.111 The drug is extensively (about 93%) bound to plasma protein.111
Cyclobenzaprine is extensively metabolized by both oxidative and conjugative pathways.1, 110, 113, 115 Hepatic cytochrome P-450 (CYP) 3A4, 1A2, and (to a lesser extent) 2D6 isoenzymes are responsible for oxidative N -demethylation of the drug.1 Orally administered cyclobenzaprine is excreted in urine principally as inactive glucuronide metabolites; less than 1% of the drug is excreted renally as unchanged drug.1, 111, 112, 113, 114 Elimination of the drug is slow; plasma clearance is 700 mL/minute per 1.73 m2 and the effective elimination half-life is about 18 hours (range: 8-37 hours).1, 110 Decreased clearance and increased plasma concentrations of the drug occur in the elderly and those with hepatic impairment.1 (See Cautions: Precautions and Contraindications and see Cautions: Geriatric Precautions.)
Cyclobenzaprine is a centrally acting skeletal muscle relaxant that is structurally and pharmacologically related to the tricyclic antidepressants.1, 101 Cyclobenzaprine hydrochloride occurs as a white crystalline powder and is freely soluble in water and in alcohol. The drug has a pKa of 8.47.1, 101
Commercially available cyclobenzaprine hydrochloride immediate-release tablets should be stored at a controlled room temperature of 20-25°C; the extended-release capsules should be stored in tight, light-resistant containers at 25°C, but may be exposed to temperatures ranging from 15-30°C.1, 101
Additional Information
For further information on cautions, acute toxicity, and drug interactions of cyclobenzaprine hydrochloride, see the Tricyclic Antidepressants General Statement 28:16.04.28.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules, extended-release | 15 mg* | ||
Cyclobenzaprine Hydrochloride Extended-release Capsules | ||||
30 mg* | Amrix® | Teva | ||
Cyclobenzaprine Hydrochloride Extended-release Capsules | ||||
Tablets, film-coated, immediate-release | 5 mg* | Cyclobenzaprine Hydrochloride Tablets | ||
7.5 mg* | Cyclobenzaprine Hydrochloride Tablets | |||
10 mg* | Cyclobenzaprine Hydrochloride Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions February 24, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Mylan. Cyclobenzaprine hydrochloride film-coated tablets prescribing information. Morgantown, WV: 2015 Sept.
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102. Liebelt EL, Francis PD. Cyclic Antidepressants. In: Goldfrank's Toxological Emergencies. 7th Ed. 2002. McGraw-Hill New York, NY.
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107. Institute for Clinical Systems Improvement. Health care guideline: adult acute and subacute low back pain. 15th ed. Bloomington, MN; 2012 Jan. From the ICSI website [Web]
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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. [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. [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. [PubMed 978450]
209. Qaseem A, Wilt TJ, McLean RM et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med . 2017; 166:514-530. [PubMed 28192789]
210. Friedman BW, Cisewski D, Irizarry E et al. A Randomized, Double-Blind, Placebo-Controlled Trial of Naproxen With or Without Orphenadrine or Methocarbamol for Acute Low Back Pain. Ann Emerg Med . 2018; 71:348-356.e5. [PubMed 29089169]
211. Spence MM, Shin PJ, Lee EA et al. Risk of injury associated with skeletal muscle relaxant use in older adults. Ann Pharmacother . 2013 Jul-Aug; 47:993-8. [PubMed 23821610]
212. Friedman BW, Irizarry E, Solorzano C et al. A Randomized, Placebo-Controlled Trial of Ibuprofen Plus Metaxalone, Tizanidine, or Baclofen for Acute Low Back Pain. Ann Emerg Med . 2019; [PubMed 30955985]
213. Friedman BW, Dym AA, Davitt M et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA . 2015; 314:1572-80. [PubMed 26501533]