OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Meprobamate – Generic

DRUG CLASS

Sedatives and Hypnotics

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Meprobamate	57-53-4	C9-H18-N2-O4

ANNOTATED BIBLIOGRAPHY

References updated: 21 January 2020

• Zimmerman HJ. Psychotropic and anticonvulsant agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 483-516.

  (Expert review of hepatotoxicity published in 1999; mentions that there have been three reported instances of liver injury attributed to meprobamate, but clinical features are not specifically discussed).
• Kanel GC. Histopathology of drug-induced liver disease. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 2nd ed. New York: Informa Healthcare USA, 2007, p. 284.

  (Meprobamate is listed as causing cholestasis with inflammation, but is not specifically discussed).
• Mihic SJ, Mayfield J, Harris RA. Hypnotics and sedatives. In, Brunton LL, Chabner BA Hillal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 339-54.

  (Textbook of pharmacology and therapeutics).
• Selling LS. Clinical study of a new tranquilizing drug; use of miltown(2-methyl-2-n-propyl-1,3-propanediol dicarbamate). J Am Med Assoc. 1955;157:1594–6. [PubMed: 14367012]

  (Among 187 patients with anxiety treated with meprobamate in a private practice, 64 recovered, 88 were improved, 35 were not improved and 3 patients developed allergic reactions; states that meprobamate "is not habit forming", but does not mention liver complications).
• Friedman HT, Marmelzat WL. Adverse reactions to meprobamate. J Am Med Assoc. 1956;162:628–30. [PubMed: 13366645]

  (Description of 7 cases of severe adverse events due to meprobamate, including rash [n=5], ocular palsy and severe diarrhea; no mention of liver injury).
• Ewing JA, Fullilove RE. Addiction to meprobamate. N Engl J Med. 1957;257:76–7. [PubMed: 13452049]

  (32 year old man taking 4 to 8 g of meprobamate daily developed headaches, muscle twitching, anxiety and somatic complaints during withdrawal).
• Haizlip TM, Ewing JA. Meprobamate habituation: a controlled clinical study. N Engl J Med. 1958;258:1181–6. [PubMed: 13552940]

  (75 residents of a State mental hospital were given meprobamate [3.2 and 6.4 g daily] or placebo for 40 days and then "surreptitiously" switched to placebo; withdrawal symptoms included insomnia, anxiety, tremors, nausea, hallucinations, acute psychosis and convulsions; no hepatic complications mentioned).
• Cowger ML, Labbe RF. Contraindications of biological-oxidation inhibitors in the treatment of porphyria. Lancet. 1965;1(7376):88–9. [PubMed: 14234213]

  (Mentions that clinical relapses of acute intermittent porphyria have occurred with drugs other than barbiturates, including chlordiazepoxide and meprobamate).
• Ayd FJ Jr. Meprobamate: A decade of experience. Psychosomatics. 1964;5:82–7. [PubMed: 14130886]

  (Review of the safety and efficacy of meprobamate after a decade of its wide scale clinical use; states "that meprobamate is free from hepatotoxicity is incontrovertible").
• Maddock RK Jr, Bloomer HA. Meprobamate overdosage. Evaluation of its severity and methods of treatment. JAMA. 1967;201:999–1003. [PubMed: 6072491]

  (10 patients with meprobamate overdose [1.6 to 30 g], ages 16 to 48 years, 7 women, 8 in coma, 1 died; plasma levels correlated with coma state and there was rapid renal clearance; no mention of liver injury).
• Schwartz HS. Acute meprobamate poisoning with gastrotomy and removal of a drug-containing mass. N Engl J Med. 1976;295:1177–8. [PubMed: 980021]

  (56 year old woman developed coma and respiratory failure after overdose of 36 g of meprobamate, with persistent high levels in serum, gastroscopy demonstrating a mass of undigested meprobamate tablets in the stomach, ultimately requiring surgical removal; no mention of liver injury).
• Crome P, Higgenbottom T, Elliott JA. Severe meprobamate poisoning: successful treatment with haemoperfusion. Postgrad Med J. 1977;53:698–9. [PMC free article: PMC2496842] [PubMed: 593997]

  (56 year old woman with meprobamate overdose developed coma and respiratory depression, improved by hemoperfusion with charcoal column; no mention of liver injury).
• Kintz P, Tracqui A, Mangin P, Lugnier AA. Fatal meprobamate self-poisoning. Am J Forensic Med Pathol. 1988;9:139–40. [PubMed: 3381792]

  (35 year old man found dead with lethal levels of meprobamate in blood; no description of liver histology).
• Littrell RA, Sage T, Miller W. Meprobamate dependence secondary to carisoprodol (Soma) use. Am J Drug Alcohol Abuse. 1993;19:133–4. [PubMed: 8438828]

  (37 year old woman was found to have meprobamate on urine screening after a motor vehicle accident, but denied taking meprobamate, but did admit to use of carisoprodol which she was later found to regularly abuse).
• Bailey DN, Briggs JR. Carisoprodol: an unrecognized drug of abuse. Am J Clin Pathol. 2002;117:396–400. [PubMed: 11888078]

  (Over a 6 month period, 19 patients were found to have carisoprodol in urine on comprehensive drug screens, 12 with decrease in level of consciousness; liver injury not mentioned).
• Buire AC, Vitry F, Hoizey G, Lamiable D, Trenque T. Overdose of meprobamate: plasma concentration and Glasgow Coma Scale. Br J Clin Pharmacol. 2009;68:126–7. [PMC free article: PMC2732949] [PubMed: 19660012]

  (Among 59 cases of meprobamate overdose, plasma levels correlated roughly with degree of coma; only one patient died).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected from 2004 to 2008, none were attributed to meprobamate).
• Fathallah N, Zamy M, Slim R, Fain O, Hmouda H, Bouraoui K, Ben Salem C, Biour M. Acute pancreatitis in the course of meprobamate poisoning. JOP. 2011;12:404–6. [PubMed: 21737904]

  (43 year old woman took an overdose of meprobamate [60 g] and was admitted in stupor and found to have pancreatitis [bilirubin 1.0 mg/dL, ALT 65 U/L, Alk P 115 U/L, lipase 21.3 times ULN], resolving with temporary ventilator support and hydration).
• Herzberg D. Blockbusters and controlled substances: Miltown, Quaalude, and consumer demand for drugs in postwar America. Stud Hist Philos Biol Biomed Sci. 2011;42:415–26. [PubMed: 22035715]

  (History of discovery, approval, marketing and subsequent wide scale use and abuse of meprobamate).
• Reeves RR, Burke RS, Kose S. Carisoprodol: update on abuse potential and legal status. South Med J. 2012;105:619–23. [PubMed: 23128807]

  (Review of the clinical features and frequency of carisoprodol abuse which increased between 2001 and 2008 and decreased with the introduction of restrictions on its sale; carisoprodol was classified as a schedule IV controlled substance in the US starting in January 2012).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A, Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America: an analysis of published reports. Ann Hepatol. 2014;13:231–9. [PubMed: 24552865]

  (Among 176 reports of drug induced liver injury from Latin America published between 1996 and 2012, none were attributed to meprobamate).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to sedatives, meprobamate or carisoprodol).