Section 09 · Monograph

Cyclobenzaprine

Reviewed Nov 2026FDA label

FlexerilMuscle relaxant (TCA-like)

Indications

Adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions (immediate-release and extended-release [Amrix] formulations); note this is FDA-labeled for musculoskeletal spasm, not for spasticity from upper motor neuron/neurologic disease — it is NOT indicated for spasticity due to CNS disorders such as cerebral palsy, spinal cord injury, or MS.FDA-labeled
Limited to short-term use (up to 2-3 weeks) per FDA labeling, as efficacy beyond that period has not been established.FDA-labeled

Fibromyalgia-associated pain/sleep disturbance, often at low dose (e.g., 5 mg at bedtime) — supported by some clinical trial data, not an FDA-approved indication.Off-label
Temporomandibular joint (TMJ) disorder-associated muscle spasm (off-label, limited evidence).Off-label
Adjunct in myofascial pain syndrome.Off-label

Centrally acting skeletal muscle relaxant, structurally related to the tricyclic antidepressants (shares a tricyclic core similar to amitriptyline).
Believed to act primarily within the CNS at the level of the brainstem, rather than at the spinal cord or neuromuscular junction.
Reduces tonic somatic motor activity, influencing both gamma and alpha motor neuron systems, thought to occur through its effect on the descending serotonergic pathways and locus coeruleus.
Has anticholinergic and antihistaminic activity contributing to sedation and dry mouth; does not act directly on skeletal muscle or the neuromuscular junction.

Immediate-release: 5 mg orally three times daily initially; may increase to 7.5-10 mg three times daily as needed/tolerated. Maximum studied dose 30 mg/day (in divided doses); limit use to 2-3 weeks.
Extended-release (Amrix): 15 mg orally once daily; may increase to 30 mg once daily based on response/tolerability.
Do not use for periods longer than 2-3 weeks per labeling.

Hepatic impairment (mild) and elderly patients: use lower dose — start at 5 mg (IR) and titrate slowly, or 15 mg once daily (ER); use with caution due to increased plasma concentrations and anticholinergic/sedative sensitivity.
Not recommended in patients with moderate-to-severe hepatic impairment.

Concomitant use with monoamine oxidase inhibitors (MAOIs), or use within 14 days of discontinuing an MAOI — risk of hyperpyretic crisis, seizures, and death.
Acute recovery phase of myocardial infarction.
Arrhythmias, heart block or conduction disturbances, congestive heart failure.
Hyperthyroidism.
Known hypersensitivity to cyclobenzaprine or any component of the formulation.

MAOIs — contraindicated; risk of hyperpyretic crisis, seizures, death.
Serotonergic drugs (SSRIs, SNRIs, TCAs, tramadol, triptans, bupropion, meperidine, lithium) — increased risk of serotonin syndrome.
CNS depressants (alcohol, benzodiazepines, opioids, barbiturates) — additive sedation/CNS depression.
Anticholinergic drugs — additive anticholinergic effects (dry mouth, urinary retention, constipation, blurred vision, confusion).
Tramadol — increased seizure risk in combination.
Drugs that prolong QT / affect cardiac conduction — use caution given structural similarity to TCAs and reports of arrhythmia in overdose.

Very common: dry mouth (up to ~27% IR / 14-19% ER), somnolence/drowsiness (up to ~39% IR), dizziness, fatigue.
Common: headache, nausea, constipation, blurred vision, nervousness/anxiety, difficulty concentrating.
Serious (rare): serotonin syndrome (with serotonergic drugs), seizures, cardiac arrhythmias/conduction disturbances, hepatotoxicity, hypersensitivity reactions, hallucinations, and significant CNS/anticholinergic toxicity in overdose (can mimic TCA overdose).

Duration of therapy — reassess need for continued use beyond 2-3 weeks.
Sedation and anticholinergic burden, particularly in elderly patients (fall risk, cognitive impairment).
Signs/symptoms of serotonin syndrome when combined with other serotonergic agents.
Cardiac status (ECG if overdose suspected or in patients with cardiac risk factors) given TCA-like structure.
Liver function periodically with prolonged use, particularly in hepatic impairment.

Pregnancy: Category B (older FDA classification) — animal reproduction studies did not demonstrate harm to the fetus, but there are no adequate and well-controlled studies in pregnant women; use only if clearly needed.
Lactation: not known whether cyclobenzaprine is excreted in human milk; given structural similarity to tricyclic antidepressants (which are excreted in breast milk), caution should be exercised when administered to a nursing mother.