OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Zaleplon	151319-34-5	C17-H15-N5-O

ANNOTATED BIBLIOGRAPHY

References updated: 20 February 2018

• Zimmerman HJ. Anxiolytic 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 hepatotoxicity published in 1999 discusses benzodiazepines and minor tranquilizers, but not the benzodiazepine receptor agonists; "In general, the hepatotoxic potential of this widely used group of compounds seems low").
• 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. 455-6.

  (Review of hepatotoxicity of hypnotics and sedatives discusses benzodiazepines, buspirone and valerian all of which have been linked to rare cases of liver injury; no discussion of zaleplon).
• Mihic SJ, Harris RA. Hypnotics and sedatives. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 457-80.

  (Textbook of pharmacology and therapeutics).
• Israel AG, Kramer JA. Safety of zaleplon in the treatment of insomnia. Ann Pharmacother 2002; 36: 852-9. [PubMed: 11978165]

  (Review of side effects and safety of both short and long term use of zaleplon in treatment of insomnia; no mention of ALT elevations or clinically apparent liver injury).
• Roblin X, Boudemaghe T, Paris F, Pellissier L, Le Gall S. [Unexplained increase in aminotransferases and obstructive sleep apnea syndrome]. Gastroenterol Clin Biol 2002; 26: 416-7. French. [PubMed: 12070418]

  (45 year old woman found to have minor serum ALT elevations [1.5-3 times ULN] without jaundice or symptoms while taking zolpidem, which improved on stopping, but which were subsequently shown to be due to severe sleep apnea).
• Moore KA, Zemrus TL, Ramcharitar V, Levine B, Fowler DR. Mixed drug intoxication involving zaleplon ("Sonata"). Forensic Sci Int 2003; 134: 120-2. [PubMed: 12850405]

  (41 year old woman died of overdose of multiple agents including zaleplon; liver histology not mentioned).
• Drover DR. Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone. Clin Pharmacokinet 2004; 43: 227-38. [PubMed: 15005637]

  (Review of mechanism of action, pharmacology, efficacy and adverse effects of 3 non-benzodiazepine hypnotic agents: zaleplon, zolpidem and zopiclone).
• Drugs for insomnia. Treat Guidel Med Lett 2012; 10 (119): 57-60. [PubMed: 22777275]

  (Guidelines for therapy of insomnia; mentions that benzodiazepine receptor agonists such as zaleplon, benzodiazepines, ramelteon and low doses of doxepin are effective and generally safe; in discussing adverse events, makes no mention of ALT elevations or hepatotoxicity of any of the recommended agents).
• 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 a sleeping aid, despite the fact that zopiclone and zolpidem are among the 25 most commonly prescribed drugs in Iceland).
• 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 of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, but none were attributed to zaleplon or other sedatives or sleeping aids).
• 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, 82 [9%] were attributed to agents active in the central nervous system, but none were due to zaleplon or other sedatives or sleeping aids).
• Drugs for insomnia. Med Lett Drugs Ther 2015; 57 (1472): 95-8. [PubMed: 26147892]

  (Concise review of the mechanism of action, efficacy, safety and costs of drugs for insomnia including benzodiazepine receptor agonists including zaleplon as well as benzodiazepines, melatonin receptor agonists, orexin receptor antagonists and other agents including nonprescription and herbal products; no mention of ALT elevations or hepatotoxicity).