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Cyclobenzaprine

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: Amrix

Medically reviewed by Drugs.com. Last updated on Feb 24, 2020.

Introduction

Centrally acting skeletal muscle relaxant; structurally and pharmacologically related to tricyclic antidepressants.1 101

Uses for Cyclobenzaprine

Muscular Conditions

Adjunct to rest and physical therapy for the relief of muscular spasm associated with acute, painful musculoskeletal conditions.1 101

If pharmacologic therapy is required for acute low back pain (usually a benign and self-limiting condition105 106 108 ), experts state that an NSAIA or skeletal muscle relaxant may be considered.209 Skeletal muscle relaxants may provide small improvements in pain relief, but are associated with a high incidence of adverse effects (e.g., CNS effects).104 106 107 108 209 Use with caution after weighing risks against benefits.104 106 107 108

Various skeletal muscle relaxants appear to have comparable efficacy for low back pain relief.104 106 108 109

Insufficient evidence to indicate whether cyclobenzaprine enhances the effects of aspirin or other analgesics, or vice versa, in the management of painful musculoskeletal conditions.1

Cyclobenzaprine is ineffective for the treatment of cerebral or spinal disease-associated spasticity or in children with cerebral palsy.1

Cyclobenzaprine Dosage and Administration

Administration

Administer orally (as immediate-release tablets or extended-release capsules).1 101

Swallow extended-release capsules intact.101 Alternatively, may open capsules and sprinkle contents onto a tablespoon of applesauce and consume immediately without chewing; do not administer with any other food.101 Following administration, rinse mouth to ensure that all capsule contents have been swallowed.101 Discard any unused portion of capsules.101

Dosage

Available as cyclobenzaprine hydrochloride; dosage expressed in terms of the salt.1 101

Pediatric Patients

Muscular Conditions
Immediate-release Tablets
Oral

Adolescents ≥15 years of age: 5 mg 3 times daily; may increase dosage to 10 mg 3 times daily depending on response.1

Adults

Muscular Conditions
Immediate-release Tablets
Oral

5 mg 3 times daily; may increase dosage to 10 mg 3 times daily depending on response.1

Extended-release Capsules
Oral

15 mg once daily (at approximately the same time each day); some patients may require up to 30 mg once daily.101

Prescribing Limits

Pediatric Patients

Muscular Conditions
Oral

Do not administer for more than 2–3 weeks.1

Adults

Muscular Conditions
Oral

Do not administer for more than 2–3 weeks.1 101

Special Populations

Hepatic Impairment

When using the immediate-release tablets, consider less frequent dosing in patients with mild hepatic impairment; initiate with 5-mg dose and increase slowly.1 (See Hepatic Impairment under Cautions.) Use not recommended in patients with moderate or severe hepatic impairment.1

Extended-release capsules not recommended for use in patients with hepatic impairment.101

Geriatric Patients

When using the immediate-release tablets, consider less frequent dosing; initiate with 5-mg dose and increase slowly.1

Extended-release capsules not recommended for use in geriatric patients.101

Cautions for Cyclobenzaprine

Contraindications

  • Known hypersensitivity to cyclobenzaprine or any ingredient in the formulation.1 101

  • Concomitant or recent (within 14 days) therapy with MAO inhibitor.1 101

  • Acute recovery phase of MI.1 101

  • Arrhythmias, heart block or conduction disorders, or CHF.1 101

  • Hyperthyroidism.1 101

Warnings/Precautions

Warnings

Serotonin Syndrome

Serotonin syndrome reported in patients receiving concomitant therapy with serotonergic drugs.1 (See Specific Drugs under Interactions.)

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 BP, hyperthermia), and GI symptoms (e.g., nausea, vomiting, diarrhea).1

If serotonin syndrome suspected, discontinue cyclobenzaprine and any concomitant serotonergic agents; initiate supportive treatment.1 (See Advice to Patients.)

Similarity to Tricyclic Antidepressants

Shares the toxic potentials of tricyclic antidepressants; observe the usual precautions associated with tricyclic antidepressant therapy.1 a

Arrhythmias, sinus tachycardia, prolongation of the conduction time leading to MI, and stroke reported with tricyclic antidepressants.1

CNS Effects

May cause serious CNS effects, especially when recommended dosage is exceeded.1

Performance of activities requiring mental alertness or physical coordination may be impaired.1

Concurrent use of other CNS depressants may potentiate CNS depression.1 (See Specific Drugs under Interactions.)

General Precautions

Anticholinergic Effects

Potential for adverse anticholinergic effects.1 Use with caution in patients with history of urinary retention, angle-closure glaucoma, or increased intraocular pressure or in patients receiving anticholinergic drugs.1

Specific Populations

Pregnancy

Category B.1

No evidence of fetal harm or impaired fertility based on animal studies; no adequate and well-controlled studies in pregnant women.1 Use during pregnancy only if clearly needed.1

Lactation

Not known whether cyclobenzaprine is distributed into milk; however, distribution into milk is possible, since other tricyclic drugs distribute into milk.1 Use with caution.1

Pediatric Use

Immediate-release tablets: Safety and efficacy not established in children <15 years of age.1

Extended-release capsules: Safety and efficacy not established.101

Geriatric Use

Increased plasma concentrations.1

Increased frequency and severity of adverse effects (with or without concomitant drug therapy).1 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.1

Because of risk of injury, skeletal muscle relaxants should generally be avoided in geriatric patients.111 Use only if clearly needed and reduce dosage.1 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Increased plasma concentrations and susceptibility to sedation.1

Immediate-release tablets: Use with caution in patients with mild hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration.) Not recommended in patients with moderate or severe hepatic impairment.1

Extended-release capsules: Not recommended in patients with hepatic impairment.101

Common Adverse Effects

Drowsiness, dry mouth, dizziness, fatigue, headache.1

Interactions for Cyclobenzaprine

Metabolized by CYP3A4, 1A2, and (to a lesser extent) 2D6.1

Shares the drug interaction potential of tricyclic antidepressants; consider the usual interactions of tricyclic antidepressant therapy.1

Specific Drugs

Drug

Interaction

Comments

Aspirin

No substantial change in plasma concentrations or bioavailability of either drug1

CNS depressants (e.g., alcohol, barbiturates)

Additive effects1

MAO inhibitors

Possible hyperpyretic crisis, seizures, and death1

Risk of serotonin syndrome with concomitant use1 101

Cyclobenzaprine contraindicated in patients currently or recently (within 14 days) receiving an MAO inhibitor1

Naproxen

Possible increased risk of drowsiness1

Serotonergic agents (e.g., SSRIs, SNRIs, tricyclic antidepressants, tramadol, meperidine)

Serotonin syndrome reported with concomitant use1

Observe patient carefully, particularly during treatment initiation or dosage adjustments1

Discontinue immediately if serotonin syndrome suspected1

Tramadol

Increased risk of seizures1

Cyclobenzaprine Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration110 111 but appears to undergo first-pass metabolism;112 113 115 mean oral bioavailability following administration of the immediate-release tablet formulation is 33–55%.1 110 111 113 114 Undergoes enterohepatic circulation.101 110 113

Following administration of a single 15- or 30-mg dose (as extended-release capsules), peak plasma concentrations achieved in 7–8 hours.101 Following multiple-dose administration (30 mg once daily for 7 days as extended-release capsules), 2-5-fold accumulation in steady-state plasma concentrations observed.101

Food

Administration of the extended-release capsule with food increased peak plasma concentrations by 35% and systemic exposure by 20%, but did not affect time to peak plasma concentration.101

Special Populations

In patients ≥65 years of age, mean steady-state AUC following administration of immediate-release tablets is about 1.7 times greater than AUC in younger adults.1 Following administration of extended-release capsules, AUC increased by 40% and half-life is more prolonged in geriatric patients >65 years of age compared with younger adults,101

In patients with mild to moderate hepatic impairment, peak plasma concentration and AUC following administration of immediate-release tablets are twice the values in healthy individuals.1 110

Distribution

Extent

Widely distributed into most body tissues.110

Plasma Protein Binding

About 93%.111

Elimination

Metabolism

Extensively metabolized in the liver via oxidation and conjugation.1 110 112 113 115 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.1 110 112 113

Half-life

About 18 hours (range: 8–37 hours).1 110

Stability

Storage

Oral

Extended-release Capsules

Tight, light-resistant containers at 25°C (may be exposed to 15–30°C).101

Immediate-release tablets

20–25°C.1

Actions

  • CNS depressant with sedative and skeletal muscle relaxant effects.1 a

  • Precise mechanism of action not known.1 a Does not directly relax skeletal muscle and, unlike neuromuscular blocking agents, does not depress neuronal conduction, neuromuscular transmission, or muscle excitability.1 a

  • Like tricyclic antidepressants, potentiates the effects of norepinephrine and has anticholinergic effects.1 a

Advice to Patients

  • Potential for drug to impair mental alertness and physical coordination, particularly when used with alcohol or other CNS depressants.1 Use caution when driving or operating machinery.1

  • Potential for more frequent or severe adverse effects in geriatric patients.1

  • Risk of serotonin syndrome if used concomitantly with serotonergic drugs.1 Advise patients of the symptoms of serotonin syndrome and instruct them to seek immediate medical care if they develop any such symptoms.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Cyclobenzaprine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release

15 mg*

Amrix

Teva

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

AHFS DI Essentials™. © Copyright 2020, Selected Revisions February 24, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

1. Mylan. Cyclobenzaprine hydrochloride film-coated tablets prescribing information. Morgantown, WV: 2015 Sept.

101. Teva. Amrix (Cyclobenzaprine hydrochloride extended-release capsules) prescribing information. North Wales, PA: 2019 Apr.

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. http://www.ncbi.nlm.nih.gov/pubmed/12809957?dopt=AbstractPlus

104. van Tulder MW, Touray T, Furlan AD et al. Muscle relaxants for non-specific low back pain. Cochrane Database Syst Rev. 2003; :CD004252. http://www.ncbi.nlm.nih.gov/pubmed/12804507?dopt=AbstractPlus

105. Roelofs PD, Deyo RA, Koes BW et al. Non-steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev. 2008; :CD000396. http://www.ncbi.nlm.nih.gov/pubmed/18253976?dopt=AbstractPlus

106. Chou R, Qaseem A, Snow V et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007; 147:478-91. http://www.ncbi.nlm.nih.gov/pubmed/17909209?dopt=AbstractPlus

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 http://www.icsi.org/low_back_pain/adult_low_back_pain__8.html

108. Toth PP, Urtis J. Commonly used muscle relaxant therapies for acute low back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and metaxalone. Clin Ther. 2004; 26:1355-67. http://www.ncbi.nlm.nih.gov/pubmed/15530999?dopt=AbstractPlus

109. See S, Ginzburg R. Skeletal muscle relaxants. Pharmacotherapy. 2008; 28:207-13. http://www.ncbi.nlm.nih.gov/pubmed/18225966?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/33029?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7082776?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/978450?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/28192789?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/29089169?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/23821610?dopt=AbstractPlus

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; http://www.ncbi.nlm.nih.gov/pubmed/30955985?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/26501533?dopt=AbstractPlus

a. AHFS Drug Information 2020. Snow EK, ed. Cyclobenzaprine hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2020.

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