Introduction
Cyclobenzaprine hydrochloride is a centrally-acting skeletal muscle relaxant structurally related to tricyclic antidepressants. First approved by the FDA in 1977, it is primarily indicated for short-term management of muscle spasm associated with acute, painful musculoskeletal conditions. While not a direct-acting relaxant, cyclobenzaprine acts primarily through central nervous system pathways to reduce muscle hyperactivity.
Mechanism of Action
Cyclobenzaprine exerts its effects primarily through central action at the brainstem, reducing somatic motor activity. The drug's exact mechanism is not fully understood but is believed to involve:
- Modulation of gamma and alpha motor neuron activity
- Reduction of tonic somatic motor activity
- Inhibition of polysynaptic reflexes
- Possible serotonergic effects similar to tricyclic antidepressants
Notably, cyclobenzaprine does not directly affect skeletal muscle fibers or the neuromuscular junction.
Indications
FDA-approved indications:- Short-term adjunctive therapy (typically 2-3 weeks) for muscle spasm associated with acute, painful musculoskeletal conditions
- Fibromyalgia management (lower doses typically used)
- Chronic pain syndromes with muscle spasm component
Dosage and Administration
Standard dosing:- Adults: 5-10 mg orally three times daily
- Maximum daily dose: 30 mg (in divided doses)
- 15-30 mg once daily
- Geriatric patients: Initiate with 5 mg, consider lower frequency
- Hepatic impairment: Use with caution; consider reduced dosing
- Renal impairment: Use with caution (limited data)
- Pediatric patients: Safety and efficacy not established
Pharmacokinetics
Absorption: Well absorbed orally; bioavailability approximately 55% Distribution: Extensive tissue distribution; protein binding ~93% Metabolism: Extensive hepatic metabolism via CYP3A4, CYP1A2, and others; forms active and inactive metabolites Elimination: Primarily renal excretion (60%) with some fecal elimination; elimination half-life 8-37 hours Onset of action: Typically within 1 hour Peak effect: 3-4 hours post-administrationContraindications
- Hypersensitivity to cyclobenzaprine or any component of the formulation
- Concomitant use of MAO inhibitors or within 14 days of MAOI therapy
- During acute recovery phase of myocardial infarction
- Arrhythmias, heart block, conduction disturbances, or congestive heart failure
- Hyperthyroidism
Warnings and Precautions
Boxed Warning: None Important precautions:- Sedation: May impair mental/physical abilities required for hazardous tasks
- Serotonin syndrome risk: Especially with concomitant serotonergic drugs
- QT prolongation: May occur, particularly in overdose or with predisposing factors
- Anticholinergic effects: Use caution in patients with urinary retention, angle-closure glaucoma, increased intraocular pressure
- Hepatic impairment: Reduced metabolism may increase toxicity risk
- Elderly patients: Increased sensitivity to adverse effects
- Withdrawal: Abrupt discontinuation after prolonged use may cause symptoms
Drug Interactions
Major interactions:- MAO inhibitors: Risk of serotonin syndrome, hypertensive crisis
- Other CNS depressants: Additive sedation (alcohol, benzodiazepines, opioids)
- Serotonergic agents: Increased serotonin syndrome risk (SSRIs, SNRIs, tramadol)
- QT-prolonging agents: Additive QT prolongation risk
- Anticholinergic agents: Additive anticholinergic effects
- CYP3A4 inhibitors/inducers: May significantly affect cyclobenzaprine levels
Adverse Effects
Common (≥1%):- Drowsiness (29-39%)
- Dry mouth (21-32%)
- Dizziness (11-16%)
- Fatigue (6%)
- Nausea (5%)
- Constipation (5%)
- Serotonin syndrome
- QT prolongation/torsades de pointes
- Seizures
- Hepatitis/liver enzyme elevations
- Anaphylaxis
- Neuroleptic malignant syndrome-like reactions
Monitoring Parameters
Baseline:- Liver function tests
- ECG (if risk factors for QT prolongation present)
- Renal function
- Assessment of fall risk in elderly
- Therapeutic response and functional improvement
- Sedation/dizziness effects
- Signs of serotonin syndrome
- Anticholinergic effects
- Fall risk assessment
- Adherence to short-term use recommendation
Patient Education
Key counseling points:- Take only as prescribed, typically for 2-3 weeks maximum
- Avoid alcohol and other CNS depressants during therapy
- May cause drowsiness - avoid driving or operating machinery until effects known
- Rise slowly from sitting/lying position to prevent dizziness
- Report any signs of allergic reaction, chest pain, rapid heartbeat, or severe dizziness
- Do not stop abruptly if taking for more than several weeks
- Use sugar-free products if dry mouth occurs (for diabetic patients)
- Inform all healthcare providers of cyclobenzaprine use before new prescriptions
References
1. FDA Prescribing Information: Cyclobenzaprine Hydrochloride Tablets 2. 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(9):1355-1367. 3. Browning R, Jackson JL, O'Malley PG. Cyclobenzaprine and back pain: a meta-analysis. Arch Intern Med. 2001;161(13):1613-1620. 4. Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage. 2004;28(2):140-175. 5. Lexicomp Online, Cyclobenzaprine Monograph. Wolters Kluwer Clinical Drug Information. 6. Micromedex Solutions, Cyclobenzaprine Drug Summary. IBM Watson Health.