CHLORZOXAZONE
Clinical safety rating
cautionComprehensive clinical and safety monograph for CHLORZOXAZONE (CHLORZOXAZONE).
Chlorzoxazone acts centrally on the spinal cord and subcortical areas of the brain to inhibit multisynaptic reflex arcs involved in producing and maintaining muscle spasm. It may also have some sedative effects.
| Metabolism | Hepatic, primarily via CYP2E1, also CYP1A2 and CYP3A4 |
| Excretion | Primarily hepatic metabolism followed by renal excretion of metabolites; <1% excreted unchanged in urine; minor biliary/fecal elimination. |
| Half-life | Terminal elimination half-life approximately 1–2 hours; clinically relevant for muscle relaxant effect duration. |
| Protein binding | Approximately 90–95% bound, primarily to albumin. |
| Volume of Distribution | 0.46–0.64 L/kg; indicates distribution into total body water. |
| Bioavailability | Oral: nearly complete; rapidly absorbed with extensive first-pass metabolism; systemic bioavailability approximately 30–50% due to first-pass effect. |
| Onset of Action | Oral: 30–60 minutes. |
| Duration of Action | 3–6 hours; effects may last up to 6 hours. |
| Molecular Weight | 169.57 |
250-500 mg orally 3-4 times daily, maximum 750 mg 4 times daily.
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation of active metabolite. |
| Liver impairment | Contraindicated in hepatic impairment; avoid use in Child-Pugh class B or C due to risk of hepatotoxicity. |
| Pediatric use | Not established; safety and efficacy not studied in pediatric patients. |
| Geriatric use | Initiate at lower end of dosing range (250 mg 3-4 times daily); monitor for CNS effects (dizziness, drowsiness) and liver function. |
| 1st trimester | Avoid: human studies suggest risk in first trimester, especially neural tube defects. Use only if benefit outweighs risk. |
| 2nd trimester | Use with caution: limited data, but no clear teratogenicity. Consider alternative muscle relaxants. |
| 3rd trimester | Use with caution: potential for neonatal hypotonia if used near term. Avoid prolonged use. |
Clinical note
Comprehensive clinical and safety monograph for CHLORZOXAZONE (CHLORZOXAZONE).
| Placental transfer | Crosses placenta; extent unknown. Likely based on molecular weight and lipophilicity. |
| Breastfeeding | Excreted into breast milk in low amounts; not expected to cause adverse effects in infants. However, monitor for sedation or poor feeding. Use caution with high doses or prolonged therapy. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Teratogenic risk in humans is not well-studied. No major teratogenic effects have been reported in animal studies. However, as with all medications, use during pregnancy only if clearly needed and after weighing risks vs. benefits. Avoid during first trimester unless necessary. |
| Fetal Monitoring | No specific fetal monitoring required. Observe for maternal adverse effects such as hepatotoxicity or hypersensitivity reactions. No routine laboratory monitoring specified. |
| Fertility Effects | No known effect on human fertility from available data. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to chlorzoxazone or any componentSevere hepatic impairmentConcurrent use of alcohol or CNS depressants (relative, but absolute per some sources)
| Precautions | May cause drowsiness, dizziness, or impaired coordination. Caution in patients with hepatic impairment. Discontinue if hypersensitivity reactions occur. Avoid concurrent use with alcohol or other CNS depressants. |
| Food/Dietary | No significant food interactions. Take with or without food. Grapefruit juice may increase drug levels; avoid large quantities. |
| Clinical Pearls | Chlorzoxazone is a centrally acting muscle relaxant used for acute musculoskeletal pain. Onset of action is within 1 hour; peak effect at 1-2 hours. Monitor for hepatotoxicity, especially with prolonged use or high doses. Can cause drowsiness and impair motor skills; avoid concurrent use with alcohol or other CNS depressants. Tablets may be crushed for patients with swallowing difficulties. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency. · May cause drowsiness or dizziness; avoid driving or operating machinery until you know how it affects you. · Avoid alcohol and other CNS depressants while taking this medication. · Report signs of liver problems: dark urine, yellowing of eyes/skin, persistent nausea, abdominal pain. · Do not suddenly stop taking if used long-term; taper under medical supervision to avoid withdrawal. |
Loading safety data…