CYCLOBENZAPRINE HYDROCHLORIDE
Clinical safety rating: safe
Animal 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs are contraindicated due to risk of serotonin syndrome and hyperpyrexia May impair mental and physical abilities required for driving.
| Breastfeeding | Cyclobenzaprine is excreted into breast milk in low amounts; the M/P ratio is unknown. Due to its anticholinergic effects, there is potential for adverse effects in the nursing infant (e.g., sedation, constipation). The American Academy of Pediatrics considers it compatible with breastfeeding, but caution is advised; alternatives may be preferred. |
| 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. |
■ FDA Black Box Warning
None
| Common Effects | Drowsiness |
| Serious Effects |
["Hypersensitivity to cyclobenzaprine or any component of the formulation","Concomitant use or within 14 days of MAO inhibitors (hypertensive crisis risk)","Acute recovery phase after myocardial infarction","Arrhythmias, heart block, or conduction disturbances","Hyperthyroidism","Severe hepatic impairment"]
| 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"] |
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| 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. |