MEPROBAMATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEPROBAMATE (MEPROBAMATE).
Meprobamate is a carbamate derivative that acts as a CNS depressant. It potentiates GABAergic inhibition and may inhibit excitatory neurotransmission, producing anxiolytic, sedative, and muscle relaxant effects. It also affects the thalamus and limbic system.
| Metabolism | Primarily hepatic via CYP2C19 and other pathways; metabolites include meprobamate-N-glucuronide and hydroxy-meprobamate. Less than 10% excreted unchanged in urine. |
| Excretion | Renal: ~90% as unchanged drug and metabolites (including glucuronide conjugate and meprobamate hydroxylated metabolite). Fecal: <1%. Biliary: minimal. |
| Half-life | 10-12 hours (terminal half-life); may be prolonged in hepatic impairment. |
| Protein binding | 15-25% bound to albumin. |
| Volume of Distribution | ~0.7 L/kg; distributes into total body water. |
| Bioavailability | Oral: ~100% (well absorbed from gastrointestinal tract). |
| Onset of Action | Oral: 30-60 minutes (anxiolytic effect). |
| Duration of Action | 6-8 hours (sedative effect); anxiolytic effects may persist longer. |
400-800 mg orally 3-4 times daily; maximum 2.4 g/day.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: administer every 9-12 hours; GFR <10 mL/min: administer every 12-18 hours; hemodialysis: dose after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use due to risk of hepatic encephalopathy. |
| Pediatric use | Children 6-12 years: 100-200 mg orally 2-3 times daily; maximum 600 mg/day. Weight-based: 25 mg/kg/day divided 3-4 times daily. |
| Geriatric use | Initiate at lower doses (200 mg 2-3 times daily) due to increased sensitivity and renal clearance decline; maximum 800 mg/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEPROBAMATE (MEPROBAMATE).
| Breastfeeding | Meprobamate is excreted into breast milk with a milk-to-plasma ratio of approximately 2-4. Cases of drowsiness, poor feeding, and weight loss in infants have been reported. The American Academy of Pediatrics considers use with caution; avoid if alternative agents available, especially in neonates or preterm infants. |
| Teratogenic Risk | First trimester: Possible increased risk of congenital malformations, particularly cardiovascular defects, based on limited human data; animal studies show embryotoxicity. Second and third trimesters: Neonatal withdrawal syndrome (tremors, irritability, poor feeding) if used near term; also risk of respiratory depression and hypotonia. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["History of porphyria","Hypersensitivity to meprobamate or other carbamate derivatives","Concurrent use with alcohol or other CNS depressants (relative)","Pregnancy (especially first trimester; use only if clearly needed)","Nursing mothers (relative; excreted in breast milk)"]
| Precautions | ["Risk of dependence, abuse, and withdrawal reactions (including seizures) with prolonged use","May cause drowsiness, dizziness, and impaired motor skills; caution with driving or hazardous activities","Avoid abrupt discontinuation; taper dose","Potential for overdose, especially when combined with other CNS depressants","Use with caution in patients with hepatic or renal impairment","Elderly patients may be more sensitive to side effects"] |
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| Fetal Monitoring | Monitor for maternal CNS depression, respiratory depression, and hypotension. Fetal monitoring (non-stress test or biophysical profile) in third trimester if used near term. Neonatal monitoring for signs of withdrawal or sedation after delivery. |
| Fertility Effects | Limited data in humans. Animal studies suggest no significant effect on fertility. In males, possible reduction in libido or erectile dysfunction at high doses, but no documented impairment of spermatogenesis or female fertility. |