cyclobenzaprine (Rx)

>10%

Drowsiness (up to 39% immediate-release; 100% extended-release)

Dry mouth (21-32%)

Dizziness (3-11%)

1-10%

Pharyngitis (1-3%)

Headache (1-5%)

Fatigue (6%)

Palpitations (6%)

Bad taste in mouth (1-6%)

Indigestion (4%)

Blurred vision (3%)

Constipation (1-3%)

Asthenia (1-3%)

Confusion (1-3%)

Nausea (1-3%)

Nervousness (1-3%)

<1%

Arrhythmia

Hypotension

Palpitation

Syncope

Tachycardia

Vasodilation

Cardiac dysrhythmia (rare)

Cholestasis (rare)

Hepatitis

Jaundice

Anaphylaxis (rare)

Immune hypersensitivity reaction

Postmarketing Reports

Serotonin syndrome

Hypertension

Stroke

Heart block

Myocardial infarction

Contraindications

Hypersensitivity to drug or formulation components

Hyperthyroidism

During the acute recovery phase of myocardial infarction and in patients with arrhythmia, heart block or conduction disturbances, or congestive heart failure

Concomitant use or within 14 days of discontinuing MAO inhibitors

Hyperpyretic crisis seizures and deaths have occurred in patients receiving cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitors

Cautions

Use only for short periods (2-3 wk)

Use caution in urinary retention, narrow-angle glaucoma or IOP, or concomitant use of other anticholinergic drugs

May cause drowsiness/dizziness; do not ingest alcohol or other CNS depressants; may impair ability to operate heavy machinery

May take with food to avoid stomach upset

Serotonin syndrome reported when coadministered with other drugs that increase serotonin (eg, SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors [see also Contraindications])

Not effective for treatment of spasticity associated with cerebral/spinal cord disease or for pediatric cerebral palsy

Elderly patients may be more prone to adverse effects and require dose/frequency reduction

Use immediate release with caution in hepatic impairment; extended-release form not recommended with hepatic impairment

Pregnancy

Available data from case reports with use in pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal data

• In rats, decreased pup body weight and survival was noted at cyclobenzaprine doses ≥10 mg/kg/day (approximately ≥3 times maximum recommended human dose (MRHD) of 30 mg/day), when administered orally during pregnancy and lactation

Lactation

There are no data on presence of drug in either human or animal milk, the effects on a breastfed infant, or effects on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition.

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Relieves local skeletal muscle spasm; clinical response similar to diazepam

Structurally related to cyclic antidepressants, and pharmacologic effects are similar, including reserpine antagonism, norepinephrine potentiation, potent peripheral and central anticholinergic effects, and sedation; reduces tonic somatic motor activity influencing alpha and gamma motor neurons

Absorption

Onset: 1 hr

Duration: 12-24 hr

Bioavailability: 33-55%

Peak plasma time: 7-8 hr

Peak plasma concentration: 15-25 ng/mL

Distribution

Protein bound: 93%

Metabolism

Hepatic via CYP3A4, 1A2, and 2D6; may undergo enterohepatic recirculation

Elimination

Half-life: 8-37 hours (immediate release); 32-33 hr (extended release)

Excretion: Urine, feces