OVERVIEW

CASE REPORT

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Triazolam – Generic, Halcion®

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
Triazolam	28911-01-5	C17-H12-Cl2-N4

CITED REFERENCES

1.

Cobden I, Record CO, White RWB. Fatal intrahepatic cholestasis associated with triazolam. Postgrad Med J. 1981;57:730–1. [PMC free article: PMC2426204] [PubMed: 6122205]

ANNOTATED BIBLIOGRAPHY

References updated: 24 January 2017

• Zimmerman HJ. Benzodiazepines. 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. 491-3.

  (Expert review of benzodiazepines and liver injury published in 1999; mentions rare instances of cholestatic hepatitis have been reported due to alprazolam, chlordiazepoxide, diazepam, flurazepam, and triazolam, and hepatocellular injury with clorazepate and clotiazepam, but no reports of hepatic injury with lorazepam, oxazepam or temazepam).
• Larrey D, Ripault MP. Anxiolytic agents. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, p. 455.

  (Review of drug induced liver injury mentions that rare instances of acute liver injury [usually cholestatic] have been reported with alprazolam, clonazepam, chlordiazepoxide, diazepam, flurazepam and triazolam).
• Mihic SJ, Mayfield J, Harris RA. Hypnotics and sedatives. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 339-53.

  (Textbook of pharmacology and therapeutics).
• Cobden I, Record CO, White RWB. Fatal intrahepatic cholestasis associated with triazolam. Postgrad Med J. 1981;57:730–1. [PMC free article: PMC2426204] [PubMed: 6122205]

  (44 year old man developed jaundice after 5 months of intermittent triazolam therapy for insomnia [bilirubin 10.6 mg/dL, AST 97 U/L and Alk P 104 U/L]; jaundice deepened and patient died, autopsy showed intrahepatic cholestasis without obstruction or cirrhosis: Case 1).
• Davion T, Capron-Chivrac D, Andrejak M, Capron JP. Gastroenterol Clin Biol. 1985;9:117–26. [Hepatitis due to antiepileptic agents] [PubMed: 3920108]

  (Review of hepatotoxicity of anticonvulsants; among benzodiazepines, cases of cholestatic hepatitis have been linked to chlordiazepoxide and diazepam, but liver injury from this class of drugs is exceptionally rare).
• Hindmarch I, Fairweather DB, Rombaut N. Adverse events after triazolam substitution. Lancet. 1993;341:55. [PubMed: 8093301]

  (Survey of UK physicians, one year after withdrawal of triazolam in the UK, found higher rate of adverse reactions [largely CNS] with replacements such as temazepam, loprazolam, nitrazepam, and lormetazepam, but no mention of hepatotoxicity).
• Lewis JH, Zimmerman HJ. Drug- and chemical-induced cholestasis. Clin Liver Dis. 1999;3:433–64. vii. Erratum in: Clin Liver Dis 1999; 3: 917. [PubMed: 11291233]

  (Review of drug induced cholestatic syndromes, listing many causes including chlordiazepoxide and flurazepam; “Benzodiazepines may cause cholestatic injury, although this is rare”).
• Sabaté M, Ibáñez L, Pérez E, Vidal X, Buti M, Xiol X, Mas A, et al. Risk of acute liver injury associated with the use of drugs: a multicentre population survey. Aliment Pharmacol Ther. 2007;25:1401–9. [PubMed: 17539979]

  (Among 126 cases of drug induced liver injury seen in Spain between 1993-2000, 20 were attributed to benzodiazepines including 5 for clorazepate, 5 alprazolam, 6 lorazepam and 4 diazepam, but compared to controls, relative risk of injury was increased only for clorazepate [8.3: estimated frequency 3.4 per 100,000 person-year exposures]).
• 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 attributed to a benzodiazepine).
• Björnsson E. Hepatotoxicity associated with antiepileptic drugs. Acta Neurol Scand. 2008;118:281–90. [PubMed: 18341684]

  (Review of hepatotoxicity of all anticonvulsants focusing upon phenytoin, valproate, carbamazepine; “furthermore, hepatoxicity has not been convincingly shown to be associated with the use of benzodiazepines”).
• Reuben A, Koch DG, Lee WM., Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52:2065–76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none were linked to a benzodiazepine).
• Drugs for insomnia. Treat Guidel Med Lett. 2012;10(119):57–60. [PubMed: 22777275]

  (Guidelines for therapy of insomnia mentions that benzodiazepines are controlled substances and when used for sleep may impair next day performance).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419–25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none were attributed to triazolam or any other benzodiazepine, despite the fact that millions of prescriptions for them are filled yearly).
• 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]

  (Systematic review of literature on drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, none of which were attributed to a benzodiazepine).
• 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;148:1340–1352.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, no cases were attributed to triazolam or any other benzodiazepine).
• Drugs for chronic insomnia. Med Lett Drugs Ther. 2023;65:1–6. [PubMed: 36630579]

  (Concise review of drugs for chronic insomnia mentions that tolerance and dependence can occur with use of benzodiazepines and their use should be discouraged, and that benzodiazepines are CNS suppressants and can impair next day performance including driving and cause complex behavior disorders, retrograde amnesia, dependence, tolerance, abuse and rebound insomnia; no mention of ALT elevations or hepatotoxicity).