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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 on Feb 24, 2020. Written by ASHP.

Introduction

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

Uses for Cyclobenzaprine

Muscular Conditions

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

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

Various skeletal muscle relaxants appear to have comparable efficacy for low back pain relief.

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

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

Cyclobenzaprine Dosage and Administration

Administration

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

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

Dosage

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

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.

Adults

Muscular Conditions
Immediate-release Tablets
Oral

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

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.

Prescribing Limits

Pediatric Patients

Muscular Conditions
Oral

Do not administer for more than 2–3 weeks.

Adults

Muscular Conditions
Oral

Do not administer for more than 2–3 weeks.

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. (See Hepatic Impairment under Cautions.) Use not recommended in patients with moderate or severe hepatic impairment.

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

Geriatric Patients

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

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

Cautions for Cyclobenzaprine

Contraindications

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

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

  • Acute recovery phase of MI.

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

  • Hyperthyroidism.

Warnings/Precautions

Warnings

Serotonin Syndrome

Serotonin syndrome reported in patients receiving concomitant therapy with serotonergic drugs. (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).

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

Similarity to Tricyclic Antidepressants

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

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

CNS Effects

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

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

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

General Precautions

Anticholinergic Effects

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

Specific Populations

Pregnancy

Category B.

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

Lactation

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

Pediatric Use

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

Extended-release capsules: Safety and efficacy not established.

Geriatric Use

Increased plasma concentrations.

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

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

Hepatic Impairment

Increased plasma concentrations and susceptibility to sedation.

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

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

Common Adverse Effects

Drowsiness, dry mouth, dizziness, fatigue, headache.

Interactions for Cyclobenzaprine

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

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

Specific Drugs

Drug

Interaction

Comments

Aspirin

No substantial change in plasma concentrations or bioavailability of either drug

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

Additive effects

MAO inhibitors

Possible hyperpyretic crisis, seizures, and death

Risk of serotonin syndrome with concomitant use

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

Naproxen

Possible increased risk of drowsiness

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

Serotonin syndrome reported with concomitant use

Observe patient carefully, particularly during treatment initiation or dosage adjustments

Discontinue immediately if serotonin syndrome suspected

Tramadol

Increased risk of seizures

Cyclobenzaprine Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration but appears to undergo first-pass metabolism; mean oral bioavailability following administration of the immediate-release tablet formulation is 33–55%. Undergoes enterohepatic circulation.

Following administration of a single 15- or 30-mg dose (as extended-release capsules), peak plasma concentrations achieved in 7–8 hours. 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.

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.

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. 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,

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.

Distribution

Extent

Widely distributed into most body tissues.

Plasma Protein Binding

About 93%.

Elimination

Metabolism

Extensively metabolized in the liver via oxidation and conjugation. Oxidative N-demethylation mediated by CYP3A4, 1A2, and (to a lesser extent) 2D6.

Elimination Route

Eliminated mainly in urine as inactive glucuronide metabolites; <1% eliminated as unchanged drug.

Half-life

About 18 hours (range: 8–37 hours).

Stability

Storage

Oral

Extended-release Capsules

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

Immediate-release tablets

20–25°C.

Actions

  • CNS depressant with sedative and skeletal muscle relaxant effects.

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

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

Advice to Patients

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

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

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

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

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

  • Importance of informing patients of other important precautionary information. (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 2021, Selected Revisions February 24, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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