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Trade namesProSom, Eurodin, Nuctalon, others
Other namesDesmethylalprazolam
  • 8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
Clinical data
Drug classBenzodiazepines (BZDs)[1]
Main usesTrouble sleeping[1]
Side effectsDizziness, poor coordination[1]
  • US: X (Contraindicated)[2]
Routes of
By mouth
Onset of action30 min[3]
Duration of actionUp to 8 hr[4]
Typical dose1 to 2 mg HS[5]
External links
License data
Legal status
Elimination half-life10–24 hours
Chemical and physical data
Molar mass294.74 g·mol−1
3D model (JSmol)
  • ClC1=CC2=C(C=C1)N3C=NN=C3CN=C2C4=CC=CC=C4
  • InChI=1S/C16H11ClN4/c17-12-6-7-14-13(8-12)16(11-4-2-1-3-5-11)18-9-15-20-19-10-21(14)15/h1-8,10H,9H2 checkY

Estazolam, sold under the brand name ProSom among others, is a medication used to treat trouble sleeping.[1] It is taken by mouth, before bed.[1] Effects may begin in 30 minutes and last for up to 8 hours.[3][4] Use is only recommended short term.[4]

Common side effects include dizziness, daytime sleepiness, and poor coordination.[1][5] Other side effects may include aggression, anaphylaxis, decreased breathing (respiratory depression), and suicide.[1] Use in pregnancy may harm the baby.[1] It is a benzodiazepines (BZDs) and is believed to work by affecting GABA.[1]

Estazolam was patented in 1968 and came into medical use in 1975.[7] It is not approved for use in the United Kingdom.[8] In the United States 30 tablets of 2 mg costs about 18 USD as of 2021.[9] In the United States it is a Schedule 4 controlled substance due to the concerns of abuse.[1]

Medical uses

Estazolam is prescribed for the short-term treatment of insomnia.[10] It increases the time spent asleep as well as reducing awakenings during the night. Combination with non-pharmacological options for sleep management results in long-term improvements in sleep quality after discontinuation of short-term estazolam therapy.[11][12] Estazolam is also sometimes used as a preoperative sleep aid. It was found to be superior to triazolam in side effect profile in preoperative patients in a trial.[13] Estazolam also has anxiolytic properties and due to its long half life can be an effective short-term treatment for insomnia associated with anxiety.[14]


The typical dose is 1 to 2 mg before bed.[4]

Side effects

A hang-over effect commonly occurs with next day impairments of mental and physical performance.[15] Other side effects of estazolam include somnolence, dizziness, hypokinesia, and abnormal coordination.[16]

In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.[17]

Tolerance and dependence

The main safety concern of benzodiazepines such as estazolam is a benzodiazepine dependence and the subsequent benzodiazepine withdrawal syndrome which can occur upon discontinuation of the estazolam. A review of the literature found that long-term use of benzodiazepines such as estazolam is associated with drug tolerance, drug dependence, rebound insomnia and CNS related adverse effects. Estazolam should only be used short term and at the lowest effective dose to avoid complications related to long-term use. Non-pharmacological treatment options however, were found to have sustained improvements in sleep quality.[18][19] The short-term benefits of benzodiazepines on sleep begin to reduce after a few days due to tolerance to the hypnotic effects of benzodiazepines in the elderly.[20]

Special populations

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders.[21]

Regarding insomnia in the elderly there is considerable evidence of the effectiveness and durability of non-drug treatments and that these interventions are underutilized. Compared with the benzodiazepines including estazolam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, advantages in efficacy or tolerability in elderly persons. It was found agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.[22]


Alcohol enhances the sedative hypnotic properties of estazolam.[23] In package inserts, the manufacturer clearly warns about an interaction with Ritonavir, and although clinical interactions of Ritonavir with estazolam have not yet been described, the lack of clinical descriptions of the interactions does not negate the seriousness of the interaction.[24]


Estazolam is classed as a "triazolo" benzodiazepine drug.[25] Estazolam exerts its therapeutic effects via its benzodiazepines receptor agonist properties.[26] Estazolam at high doses decreases histamine turnover via its action at the benzodiazepine-GABA receptor complex in mouse brains.[27]


Peak plasma levels are achieved within 1–6 hours. Estazolam is an intermediate acting benzodiazepine. The elimination half life of estazolam is an average of 19 hours, with a range of 8–31 hours.[28][29] The major metabolite of estazolam is 4-hydroxyestazolam.[30] Other identified metabolites include 1-oxo-estazolam, 4'-hydroxy-estazolam, and benzophenone.[6]

Society and culture


A primate study found that estazolam has abuse potential.[31] Estazolam is a drug with the potential for misuse. Two types of drug misuse can occur; recreational misuse, where the drug is taken to achieve a high or when the drug is continued long term against medical advice.[32] Estazolam became notorious in 1998 when a large amount of an 'herbal sleeping mix' called Sleeping Buddha was recalled from the shelves after the FDA discovered that it contained estazolam.[33] In 2007, a Canadian product called Sleepees was recalled after it was found to contain undeclared estazolam.[34][35]


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 "Estazolam Monograph for Professionals". Archived from the original on 22 November 2021. Retrieved 16 December 2021.
  2. "Estazolam (Prosom) Use During Pregnancy". 18 September 2020. Archived from the original on 3 December 2020. Retrieved 25 October 2020.
  3. 3.0 3.1 Cacho, Valerie; Lum, Esther (2 June 2021). Integrative Sleep Medicine. Oxford University Press. p. 376. ISBN 978-0-19-088542-7. Archived from the original on 11 January 2022. Retrieved 16 December 2021.
  4. 4.0 4.1 4.2 4.3 Learning, Jones & Bartlett (11 November 2019). 2020 Nurse's Drug Handbook. Jones & Bartlett Learning. p. 438. ISBN 978-1-284-16790-0. Archived from the original on 11 January 2022. Retrieved 16 December 2021.
  5. 5.0 5.1 "Estazolam". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. Archived from the original on 6 May 2021. Retrieved 16 December 2021.
  6. 6.0 6.1 "Estazolam tablet". DailyMed. 30 September 2020. Archived from the original on 29 October 2020. Retrieved 25 October 2020.
  7. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 538. ISBN 9783527607495. Archived from the original on 2021-11-01. Retrieved 2021-09-30.
  8. Encyclopedia of Analytical Science. Elsevier. 2 April 2019. p. 257. ISBN 978-0-08-101984-9. Archived from the original on 11 January 2022. Retrieved 16 December 2021. In the United Kingdom, Etizolam, licensed only for use in India, Italy, and Japan and appearing in both diverted, but predominantly illicitly manufactured tablets has become one of the most commonly seized benzodiazepines
  9. "Estazolam Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 9 November 2016. Retrieved 16 December 2021.
  10. Cite error: Invalid <ref> tag; no text was provided for refs named NDH2020
  11. Roehrs T, Zorick F, Lord N, Koshorek GL, Roth T (June 1983). "Dose-related effects of estazolam on sleep of patients with insomnia". J Clin Psychopharmacol. 3 (3): 152–6. doi:10.1097/00004714-198306000-00002. PMID 6135720. S2CID 9143614.
  12. Rosen RC, Lewin DS, Goldberg L, Woolfolk RL (October 2000). "Psychophysiological insomnia: combined effects of pharmacotherapy and relaxation-based treatments". Sleep Med. 1 (4): 279–288. doi:10.1016/S1389-9457(00)00042-3. PMID 11040460.
  13. Mauro C, Sperlongano P (September 1987). "[Controlled clinical evaluation of 2 hypnotic triazole benzodiazepines, estazolam and triazolam, used the night before surgical interventions]". Minerva Med. (in italiano). 78 (18): 1381–4. PMID 2889169.
  14. Post GL; Patrick RO; Crowder JE; et al. (August 1991). "Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study". J Clin Psychopharmacol. 11 (4): 249–53. doi:10.1097/00004714-199108000-00005. PMID 1918423. S2CID 7890993.
  15. Müller KW, Müller-Limmroth W, Strasser H (1982). "[Alterations of sleep stage pattern in human beings and hang-over effects under the influence of estazolam/2nd Comm.: Studies on the hang-over effect in psycho-physiological performance (author's transl)]". Arzneimittelforschung (in Deutsch). 32 (4): 456–60. PMID 6125155.
  16. Pierce MW, Shu VS, Groves LJ (March 1990). "Safety of estazolam. The United States clinical experience". Am. J. Med. 88 (3A): 12S–17S. doi:10.1016/0002-9343(90)90280-Q. PMID 1968713.
  17. "FDA expands Boxed Warning to improve safe use of benzodiazepine drug". U.S. Food and Drug Administration (FDA). 23 September 2020. Archived from the original on 24 September 2020. Retrieved 23 September 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  18. Kirkwood CK (1999). "Management of insomnia". J Am Pharm Assoc (Wash). 39 (5): 688–96, quiz 713–4. doi:10.1016/S1086-5802(15)30354-5. PMID 10533351.
  19. Lee YJ (2004). "Overview of the therapeutic management of insomnia with zolpidem". CNS Drugs. 18 Suppl 1: 17–23, discussion 41, 43–5. doi:10.2165/00023210-200418001-00005. PMID 15291010. S2CID 7936406.
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  21. Authier, N.; Balayssac, D.; Sautereau, M.; Zangarelli, A.; Courty, P.; Somogyi, AA.; Vennat, B.; Llorca, PM.; Eschalier, A. (November 2009). "Benzodiazepine dependence: focus on withdrawal syndrome". Ann Pharm Fr. 67 (6): 408–13. doi:10.1016/j.pharma.2009.07.001. PMID 19900604.
  22. Bain KT (June 2006). "Management of chronic insomnia in elderly persons". Am J Geriatr Pharmacother. 4 (2): 168–92. doi:10.1016/j.amjopharm.2006.06.006. PMID 16860264.
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  24. Miura M, Ohkubo T, Sugawara K, Okuyama N, Otani K (May 2002). "Determination of estazolam in plasma by high-performance liquid chromatography with solid-phase extraction" (PDF). Anal Sci. 18 (5): 525–8. doi:10.2116/analsci.18.525. PMID 12036118.
  25. Braestrup C; Squires RF (1 April 1978). "Pharmacological characterization of benzodiazepine receptors in the brain". Eur J Pharmacol. 48 (3): 263–70. doi:10.1016/0014-2999(78)90085-7. PMID 639854.
  26. Akbarzadeh T, Tabatabai SA, Khoshnoud MJ, Shafaghi B, Shafiee A (March 2003). "Design and synthesis of 4H-3-(2-phenoxy)phenyl-1,2,4-triazole derivatives as benzodiazepine receptor agonists". Bioorg. Med. Chem. 11 (5): 769–73. doi:10.1016/S0968-0896(02)00469-8. PMID 12538007.
  27. Oishi R; Nishibori M; Itoh Y; Saeki K (May 27, 1986). "Diazepam-induced decrease in histamine turnover in mouse brain". Eur J Pharmacol. 124 (3): 337–42. doi:10.1016/0014-2999(86)90236-0. PMID 3089825.
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  29. Mancinelli A, Guiso G, Garattini S, Urso R, Caccia S (March 1985). "Kinetic and pharmacological studies on estazolam in mice and man". Xenobiotica. 15 (3): 257–65. doi:10.3109/00498258509045357. PMID 2862746.
  30. Miura M, Otani K, Ohkubo T (May 2005). "Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam". Xenobiotica. 35 (5): 455–65. doi:10.1080/00498250500111612. PMID 16012077. S2CID 10576075.
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External links

External sites: