- Michael Bodmer, MD, MSc
Michael Bodmer, MD, MSc
- Division of General Internal Medicine
- Bern University Hospital, Inselspital, Bern, Switzerland
- Pharmacoepidemiology Unit, Pharmaceutical Sciences
- University Hospital Basel, Switzerland
- Alessandro Ceschi, MD
Alessandro Ceschi, MD
- Head Division of Science
- Swiss Toxicological Information Centre, Associated Institute of the University of Zurich
- Department of Clinical Pharmacology and Toxicology
- University Hospital Zurich, Switzerland
Meprobamate is a sedative and anxiolytic medication that was marketed for decades in the United States and continues to be used in Europe. The first case of meprobamate poisoning was described in 1956 . Due to its substantial abuse potential, meprobamate is no longer recommended for treatment of insomnia and has been replaced by benzodiazepines and other agents. Although use of the drug is declining, significant meprobamate overdose remains a life-threatening emergency.
This topic will review the basic pharmacology, clinical presentation, and management of meprobamate poisoning. Discussions of the general approach to the management of poisoned patients and detailed management of other toxins are found elsewhere. (See "General approach to drug poisoning in adults" and "Initial management of the critically ill adult with an unknown overdose".)
Meprobamate poisoning is rare and most cases involve suicide attempts . In France, meprobamate has been used more widely and the drug was involved in approximately 7 percent of psychotropic poisonings in 2005 . Mortality in cases of overdose has ranged between 1.7 and 5 percent [4-6]. Meprobamate ingestion is associated with an increased risk of intensive care unit (ICU) admission (adjusted odds ratio [OR] = 2.71; 95% CI: 1.27-5.81) .
Meprobamate is a carbamate which acts primarily as a sedative by increasing GABAA-mediated neurotransmission in a manner similar to barbiturates [8,9]. Carisoprodol, prescribed as a centrally acting muscle relaxant, is mainly metabolized to meprobamate by cytochrome P450 2C19, shares properties with meprobamate, and also has significant potential for abuse [10-12].
PHARMACOKINETICS AND TOXICOKINETICS
After oral ingestion of a therapeutic dose, meprobamate is rapidly absorbed from the gastrointestinal tract and peak plasma concentrations are reached within one to three hours [13,14]. Protein binding is negligible (14 to 24 percent). The drug’s volume of distribution is reported to be 0.70 L/kg, and is not significantly altered in overdose. A standard single therapeutic dose for an adult ranges from 200 to 800 mg. Significant toxicity is likely with ingestions of 4 to 5 g or more [3,4].
- SHANE AM, HIRSCH S. Three cases of meprobamate poisoning. Can Med Assoc J 1956; 74:908.
- Lambert WE, De Leenheer AP, Van Bocxlaer JF, Piette M. Meprobamate intoxication: rare and difficult to find. J Toxicol Clin Toxicol 1992; 30:683.
- Charron C, Mekontso-Dessap A, Chergui K, et al. Incidence, causes and prognosis of hypotension related to meprobamate poisoning. Intensive Care Med 2005; 31:1582.
- Buire AC, Vitry F, Hoizey G, et al. Overdose of meprobamate: plasma concentration and Glasgow Coma Scale. Br J Clin Pharmacol 2009; 68:126.
- Gaultier M, Fournier E, Bismuth C, et al. [Acute poisoning by meprobamate. Apropos of 141 cases]. Bull Mem Soc Med Hop Paris 1968; 119:675.
- Mounier B, Pons B, Delavenne X, et al. [Severe meprobamate poisoning: description of 146 cases in a French department]. Therapie 2012; 67:183.
- Maignan M, Pommier P, Clot S, et al. Deliberate drug poisoning with slight symptoms on admission: are there predictive factors for intensive care unit referral? A three-year retrospective study. Basic Clin Pharmacol Toxicol 2014; 114:281.
- Rho JM, Donevan SD, Rogawski MA. Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate. J Pharmacol Exp Ther 1997; 280:1383.
- Roache JD, Griffiths RR. Lorazepam and meprobamate dose effects in humans: behavioral effects and abuse liability. J Pharmacol Exp Ther 1987; 243:978.
- Heacock C, Bauer MS. Tolerance and dependence risk with the use of carisoprodol. Am Fam Physician 2004; 69:1622.
- Reeves RR, Carter OS, Pinkofsky HB, et al. Carisoprodol (soma): abuse potential and physician unawareness. J Addict Dis 1999; 18:51.
- Reeves RR, Pinkofsky HB, Carter OS. Carisoprodol: a drug of continuing abuse. J Am Osteopath Assoc 1997; 97:723.
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- Micromedex Healthcare Series. Thomson Reuters, Greenwood Village, Colorado, 2010.
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- Jacobsen D, Wiik-Larsen E, Saltvedt E, Bredesen JE. Meprobamate kinetics during and after terminated hemoperfusion in acute intoxications. J Toxicol Clin Toxicol 1987; 25:317.
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- Allen MD, Greenblatt DJ, Noel BJ. Meprobamate overdosage: a continuing problem. Clin Toxicol 1977; 11:501.
- Eeckhout E, Huyghens L, Loef B, et al. Meprobamate poisoning, hypotension and the Swan-Ganz catheter. Intensive Care Med 1988; 14:437.
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- Bourry J, Sainty JM, Roux JJ, Ressiot G. [Acute pancreatitis in the course of meprobamate poisoning. Possible role of pressor amine therapy]. Nouv Presse Med 1976; 5:1918.
- Fathallah N, Zamy M, Slim R, et al. Acute pancreatitis in the course of meprobamate poisoning. JOP 2011; 12:404.
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- Delavenne X, Gay-Montchamp JP, Basset T. HPLC MS/MS method for quantification of meprobamate in human plasma: application to 24/7 clinical toxicology. J Chromatogr B Analyt Technol Biomed Life Sci 2011; 879:215.
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- Crome P, Higgenbottom T, Elliott JA. Severe meprobamate poisoning: successful treatment with haemoperfusion. Postgrad Med J 1977; 53:698.
- Hoy WE, Rivero A, Marin MG, Rieders F. Resin hemoperfusion for treatment of a massive meprobamate overdose. Ann Intern Med 1980; 93:455.
- Lin JL, Lim PS, Lai BC, Lin WL. Continuous arteriovenous hemoperfusion in meprobamate poisoning. J Toxicol Clin Toxicol 1993; 31:645.
- Laroche B, Hoang The Dan P, Lapandry C, et al. [Acute meprobamate poisoning. Efficacy of peritoneal dialysis]. Cah Anesthesiol 1984; 32:677.
- PHARMACOKINETICS AND TOXICOKINETICS
- CLINICAL FEATURES OF OVERDOSE
- Clinical symptoms and signs
- - Overview
- - Cardiovascular
- - Neurologic
- - Respiratory
- - Other manifestations
- DIAGNOSTIC IMAGING
- LABORATORY EVALUATION
- Testing for meprobamate
- General evaluation
- DIFFERENTIAL DIAGNOSIS
- Initial stabilization
- Treatment of hypotension
- Gastrointestinal decontamination
- Enhanced elimination
- Ongoing treatment and disposition
- ADDITIONAL RESOURCES
- SUMMARY AND RECOMMENDATIONS