CYCLOBENZAPRINE HYDROCHLORIDE
Clinical safety rating
safeAnimal studies have demonstrated safety
Cyclobenzaprine is a centrally acting muscle relaxant that reduces tonic somatic motor activity at the supraspinal level, primarily at the brainstem reticular formation and descending pathways. It is structurally related to tricyclic antidepressants and inhibits reuptake of norepinephrine and serotonin, but the direct relationship to its muscle relaxant effects is not fully established.
| Metabolism | Hepatic metabolism primarily via CYP3A4, CYP1A2, and CYP2D6; also undergoes N-demethylation and glucuronidation. Active metabolites include norcyclobenzaprine. |
| Excretion | Renal: ~50% as unchanged drug and metabolites; Fecal: ~40% primarily as metabolites; Biliary: minimal. |
| Half-life | Terminal half-life: 18–24 hours (range 8–37 hours). Clinical context: requires multiple doses to achieve steady state (5–6 days); active metabolite norcyclobenzaprine has half-life ~30 hours. |
| Protein binding | ~93% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | ~5 L/kg (range 3–7 L/kg). Clinical meaning: extensive tissue distribution, including central nervous system. |
| Bioavailability | Oral: 33–55% due to first-pass metabolism; lower for immediate-release compared to extended-release (same extent but slower absorption). |
| Onset of Action | Oral: 1–2 hours for muscle relaxant effect. |
| Duration of Action | 10–24 hours; clinical effect may persist beyond plasma levels due to central penetration. Extended-release forms provide 24-hour duration. |
| Molecular Weight | 311.85 |
Adults: 5 mg orally three times daily; may increase to 10 mg three times daily based on response. Maximum 30 mg per day.
| Dosage form | TABLET |
| Renal impairment | No specific dosing adjustment recommended; use caution in severe renal impairment due to potential accumulation. |
| Liver impairment | Child-Pugh Class A or B: No adjustment. Child-Pugh Class C: Contraindicated due to risk of toxicity (minimal data). Use with caution in mild to moderate impairment; consider lower starting dose. |
| Pediatric use | Not recommended for children under 15 years; safety and efficacy not established. For adolescents ≥15 years: same as adult dosing. |
| Geriatric use | Start with 5 mg once daily; increase slowly to a maximum of 10 mg three times daily over 2 weeks. Increased sensitivity; monitor for anticholinergic effects and sedation. |
| 1st trimester | Cyclobenzaprine hydrochloride crosses the placenta. Limited human data; animal studies show no teratogenicity at clinically relevant doses. Use only if clearly needed. |
| 2nd trimester | Same as T1. Consider risk-benefit, especially as uterine blood flow increases in second trimester. |
| 3rd trimester | Avoid use near term due to potential for neonatal sedation, hypotonia, and respiratory depression from anticholinergic effects. |
Clinical note
MAOIs are contraindicated due to risk of serotonin syndrome and hyperpyrexia May impair mental and physical abilities required for driving.
| Placental transfer | Cyclobenzaprine crosses the placenta; degree of transfer is moderate based on molecular weight and lipophilicity. No quantitative data on fetal concentrations. |
| Breastfeeding | Cyclobenzaprine is excreted into breast milk in small amounts (estimated infant dose <1% maternal weight-adjusted dose). Monitor infant for drowsiness, hypotonia, and feeding difficulties. Use with caution, especially in neonates or preterm infants. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Cyclobenzaprine is classified as FDA Pregnancy Category B. Animal reproduction studies have not shown fetal risk, and there are no adequate and well-controlled studies in pregnant women. Risk cannot be ruled out. First trimester: Limited human data, but no structural anomalies reported. Second trimester: No specific adverse effects documented. Third trimester: Potential for neonatal withdrawal symptoms (e.g., jitteriness, respiratory depression) if used near term. |
| Fetal Monitoring | Monitor maternal heart rate and blood pressure due to potential anticholinergic effects (tachycardia, hypertension). For fetus, no specific monitoring required unless maternal toxicity occurs. Assess neonatal status if used near delivery. |
| Fertility Effects | No specific human studies on fertility. Animal studies have not reported impaired fertility. Theoretical impact due to anticholinergic effects on libido or menstrual cycles is possible but not documented. |
■ FDA Black Box Warning
None
| Common Effects | Drowsiness |
| Serious Effects |
Concomitant use with MAO inhibitors (MAOIs) or within 14 days of MAOI therapyAcute recovery phase of myocardial infarctionArrhythmias, especially heart block or QT prolongationHyperthyroidismUncontrolled narrow-angle glaucomaUrinary retention
| Precautions | Serotonin syndrome risk, especially with concomitant serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs), Sedation and impairment of motor skills; caution with driving or operating machinery, Anticholinergic effects (e.g., urinary retention, angle-closure glaucoma, constipation), Cardiovascular effects: tachycardia, QT prolongation, arrhythmias (especially in elderly or with pre-existing heart disease), Hepatic impairment: use with caution; reduced clearance in mild impairment, avoid in severe impairment, Withdrawal symptoms after abrupt discontinuation: dysphoria, anxiety, insomnia, Elderly patients: increased risk of falls, confusion, anticholinergic toxicity |
| Food/Dietary | Alcohol should be avoided due to additive CNS depression. Grapefruit juice may increase cyclobenzaprine levels (though data is limited, caution is advised). High-fat meals may delay absorption but not clinically significant. No specific dietary restrictions are required. |
| Clinical Pearls | Cyclobenzaprine is structurally related to tricyclic antidepressants and shares similar anticholinergic and sedative properties. Onset of action for muscle relaxation is typically 1 hour, but maximal effect may take several days. Avoid use in patients with hyperthyroidism, cardiac disease, or those on MAOIs. Not recommended for use longer than 2-3 weeks due to lack of evidence for chronic use. Caution in elderly due to anticholinergic effects and fall risk. |
| Patient Advice | This medication may cause drowsiness, dizziness, or blurred vision; avoid driving or operating machinery until you know how it affects you. · Do not drink alcohol or use other CNS depressants (e.g., benzodiazepines, opioids) while taking this medication, as it may increase sedation. · Take this medication exactly as prescribed, usually 3 times a day. Do not take more or less than directed. · This medication is intended for short-term use (up to 2-3 weeks) for muscle spasm. Do not use it for longer without consulting your doctor. · If you experience dry mouth, try sucking on sugar-free candy or ice chips. If you have difficulty urinating or vision changes, contact your doctor. · Do not stop taking this medication abruptly without consulting your doctor, although withdrawal is uncommon with short-term use. |
Loading safety data…