Brand name: Amrix
Drug 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

Medically reviewed by Drugs.com on Feb 14, 2024. Written by ASHP.

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 condition^{105 106 108} ), 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

Drug Interactions

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

Cyclobenzaprine Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration^{110 111} 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

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