ROBAXISAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ROBAXISAL (ROBAXISAL).
Methocarbamol is a centrally acting muscle relaxant whose exact mechanism is not fully understood, but it is believed to involve general central nervous system depression and inhibition of polysynaptic reflexes in the spinal cord. Aspirin inhibits cyclooxygenase enzymes (COX-1 and COX-2), reducing prostaglandin synthesis, which provides analgesic and anti-inflammatory effects, and also irreversibly inhibits platelet aggregation.
| Metabolism | Methocarbamol is metabolized primarily via dealkylation and glucuronidation; unknown cytochrome P450 involvement. Aspirin is hydrolyzed to salicylic acid, which is then conjugated with glycine (forming salicyluric acid) and glucuronic acid, and undergoes oxidative metabolism via CYP2C9 (minor pathway). |
| Excretion | Methocarbamol: renal (primarily as glucuronide and sulfate conjugates, with <2% unchanged); guaifenesin: renal (metabolites, <1% unchanged). No significant biliary/fecal elimination. |
| Half-life | Methocarbamol: 1.0–2.0 hours (prolonged in renal impairment); guaifenesin: approximately 1 hour. |
| Protein binding | Methocarbamol: 46–50% (primarily to albumin); guaifenesin: negligible. |
| Volume of Distribution | Methocarbamol: 0.6–0.8 L/kg; guaifenesin: not well characterized (likely <1 L/kg). |
| Bioavailability | Methocarbamol: ~100% oral (well absorbed, but extensive first-pass metabolism); guaifenesin: ~80–90% oral (undergoes first-pass metabolism). |
| Onset of Action | Oral methocarbamol: approximately 30 minutes; oral guaifenesin: 30–60 minutes. |
| Duration of Action | Methocarbamol: 4–6 hours (relaxant effect); guaifenesin: 4–6 hours (expectorant effect). |
Oral: 2 tablets (methocarbamol 750 mg / aspirin 650 mg) 4 times daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min due to aspirin component. For GFR 30-60 mL/min, reduce dose to 1 tablet 4 times daily; avoid if possible. |
| Liver impairment | Child-Pugh A: No adjustment needed. Child-Pugh B or C: Avoid use due to aspirin component (risk of bleeding) and methocarbamol metabolism concerns. |
| Pediatric use | Not recommended for use in children and adolescents due to risk of Reye's syndrome from aspirin. |
| Geriatric use | Avoid use in elderly due to increased risk of gastrointestinal bleeding, renal impairment, and drug interactions; consider alternative therapy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ROBAXISAL (ROBAXISAL).
| Breastfeeding | Limited data; methocarbamol and aspirin (in Robaxisal) are excreted in breast milk; M/P ratio not established for methocarbamol; aspirin may cause Reye's syndrome in infants; avoid breastfeeding. |
| Teratogenic Risk | First trimester: No well-controlled studies; animal data suggest risk of skeletal anomalies at high doses; avoid unless benefit outweighs risk. Second/third trimester: No known teratogenicity; preterm labor risk with high doses due to skeletal muscle relaxation. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning is present for ROBAXISAL.
| Serious Effects |
["Hypersensitivity to methocarbamol or aspirin","History of aspirin-induced asthma or NSAID-induced urticaria","Active peptic ulcer disease or gastrointestinal bleeding","Hemophilia or other bleeding disorders","Severe renal impairment (eGFR <30 mL/min)","Severe hepatic impairment","Children and teenagers with viral infections due to risk of Reye syndrome","Concurrent use of methotrexate (high dose) or anticoagulants"]
| Precautions | ["Risk of Reye syndrome with aspirin use in children or teenagers with viral illnesses","Methocarbamol may cause CNS depression (drowsiness, dizziness) and impair mental or physical abilities","Aspirin increases risk of bleeding, including gastrointestinal bleeding and intracranial hemorrhage","Methocarbamol may cause seizures in patients with known seizure disorders","Cross-allergenicity with aspirin in patients with NSAID hypersensitivity"] |
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| Monitor fetal heart rate and uterine activity with intravenous high-dose methocarbamol. Assess bleeding time in mother due to aspirin component. Observe neonate for respiratory depression if used near delivery. |
| Fertility Effects | No specific data on human fertility; animal studies show no significant effects. Aspirin may impair ovulation at high doses due to prostaglandin inhibition. |