Zolpidem

Zolpidem
Clinical data
Trade namesAmbien, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa693025
License data
Pregnancy
category
Dependence
liability		Physical: High Psychological: Moderate[3]
Addiction
liability		High[4]
Routes of
administration		By mouth, sublingual, oromucosal (spray), rectal
Drug classNonbenzodiazepine, sedative-hypnotic
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability70% (by mouth)
Protein binding92%[9]
MetabolismLiver through CYP3A4 (~60%), CYP2C9 (~20%), and CYP1A2 (~14%)[15]
Metabolites(ZCA) zolpidem 6-carboxylic acid; (ZPCA) zolpidem phenyl-4-carboxylic acid
Onset of action≤ 30 Minutes [10]
Elimination half-life2–3 hours[11][9][12]
Duration of action3 hours [13][14]
ExcretionKidney (56%)
fecal (34%)
Identifiers
  • N,N-Dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide hemitartrate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.115.604 Edit this at Wikidata
Chemical and physical data
FormulaC19H21N3O
Molar mass307.397 g·mol−1
3D model (JSmol)
Melting point193–197 °C (379–387 °F) [9]
  • CN(C)C(=O)Cc1c(nc2ccc(C)cn12)c3ccc(C)cc3
  • InChI=1S/C19H21N3O/c1-13-5-8-15(9-6-13)19-16(11-18(23)21(3)4)22-12-14(2)7-10-17(22)20-19/h5-10,12H,11H2,1-4H3 checkY
  • Key:ZAFYATHCZYHLPB-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Zolpidem, sold under the brand name Ambien among others, is a medication primarily used for the short-term treatment of sleeping problems.[11][16] Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and after behavioral changes, such as sleep hygiene, have been tried.[17][18][19] It decreases the time to sleep onset by about fifteen minutes and at larger doses helps people stay asleep longer.[7] It is taken by mouth and is available in conventional tablets, sublingual tablets, or oral spray.[11]

Common side effects include daytime sleepiness, headache, nausea, and diarrhea.[11] More severe side effects include memory problems and hallucinations.[7] While flumazenil, a GABAA–receptor antagonist, can reverse zolpidem's effects, usually supportive care is all that is recommended in overdose.[20]

Zolpidem is a nonbenzodiazepine, or Z-drug, which acts as a sedative and hypnotic.[11][20] Zolpidem is a GABAA receptor agonist of the imidazopyridine class.[11] It works by increasing GABA effects in the central nervous system by binding to GABAA receptors at the same location as benzodiazepines.[11] It generally has a half-life of two to three hours.[11] This, however, is increased in those with liver problems.[11]

Zolpidem was approved for medical use in the United States in 1992.[11][21] It became available as a generic medication in 2007.[22] Zolpidem is a schedule IV controlled substance under the Controlled Substances Act of 1970 (CSA).[7][8] More than ten million prescriptions are filled each year in the United States, making it one of the most commonly used treatments for sleeping problems.[23][24] In 2022, it was the 66th most commonly prescribed medication in the United States, with more than 9 million prescriptions.[25][26]

  1. ^ Cite error: The named reference genericnames was invoked but never defined (see the help page).
  2. ^ "Zolpidem Use During Pregnancy". Drugs.com. 30 June 2020. Archived from the original on 20 June 2020. Retrieved 14 August 2020.
  3. ^ Ries RK (2009). Principles of addiction medicine (4 ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. p. 106. ISBN 978-0-7817-7477-2. Archived from the original on 8 September 2017.
  4. ^ Victorri-Vigneau C, Gérardin M, Rousselet M, Guerlais M, Grall-Bronnec M, Jolliet P (January 2014). "An update on zolpidem abuse and dependence". Journal of Addictive Diseases. 33 (1): 15–23. doi:10.1080/10550887.2014.882725. ISSN 1055-0887. PMID 24467433.
  5. ^ "Scheduling of zolpidem (Stilnox)". Therapeutic Goods Administration (TGA). 21 February 2008. Archived from the original on 5 August 2020. Retrieved 15 August 2020.
  6. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 3 August 2023.
  7. ^ a b c d Matheson E, Hainer BL (July 2017). "Insomnia: Pharmacologic Therapy". American Family Physician. 96 (1): 29–35. PMID 28671376. Archived from the original on 19 August 2018. Retrieved 18 August 2018.
  8. ^ a b "Ambien- zolpidem tartrate tablet, film coated". DailyMed. 29 August 2019. Archived from the original on 12 August 2020. Retrieved 15 August 2020.
  9. ^ a b c Salvà P, Costa J (September 1995). "Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications". Clinical Pharmacokinetics. 29 (3): 142–153. doi:10.2165/00003088-199529030-00002. PMID 8521677. S2CID 23391285.
  10. ^ Super ER, Johnson KP (2012). "Sleep Pharmacotherapeutics for Pediatric Insomnia". Therapy in Sleep Medicine. Elsevier. pp. 457–464. doi:10.1016/b978-1-4377-1703-7.10036-2. ISBN 978-1-4377-1703-7.
  11. ^ a b c d e f g h i j "Zolpidem (Monograph)". The American Society of Health-System Pharmacists. 27 April 2023. Archived from the original on 16 March 2018. Retrieved 10 March 2024.
  12. ^ Cite error: The named reference Mendelson_2011 was invoked but never defined (see the help page).
  13. ^ Sabe M, Kashef H, Gironi C, Sentissi O (August 2019). "Zolpidem stimulant effect: Induced mania case report and systematic review of cases". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 94: 109643. doi:10.1016/j.pnpbp.2019.109643. PMID 31071363.
  14. ^ "AMBIEN- zolpidem tartrate tablet, film coated". DailyMed. 19 August 2024. Archived from the original on 6 October 2024. Retrieved 1 September 2024.
  15. ^ Von Moltke LL, Greenblatt DJ, Granda BW, Duan SX, Grassi JM, Venkatakrishnan K, et al. (July 1999). "Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations". British Journal of Clinical Pharmacology. 48 (1): 89–97. doi:10.1046/j.1365-2125.1999.00953.x. PMC 2014868. PMID 10383565.
  16. ^ Cite error: The named reference UKlabel was invoked but never defined (see the help page).
  17. ^ Cite error: The named reference NICE2014 was invoked but never defined (see the help page).
  18. ^ Cite error: The named reference EUsleep2017 was invoked but never defined (see the help page).
  19. ^ Cite error: The named reference ACP2016 was invoked but never defined (see the help page).
  20. ^ a b Gunja N (June 2013). "The clinical and forensic toxicology of Z-drugs". Journal of Medical Toxicology. 9 (2): 155–62. doi:10.1007/s13181-013-0292-0. PMC 3657020. PMID 23404347.
  21. ^ "Drug Approval Package: Ambien (Zolpidem Tartrate) NDA 19908". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 15 August 2020.
  22. ^ "FDA Approves First Generic Versions of Ambien (Zolpidem Tartrate) for the Treatment of Insomnia". U.S. Food and Drug Administration (FDA) (Press release). Archived from the original on 6 March 2010. Retrieved 24 January 2010.
  23. ^ "Zolpidem". LiverTox. Archived from the original on 16 March 2018. Retrieved 15 March 2018.
  24. ^ "Some Sleep Drugs Can Impair Driving". U.S. Food and Drug Administration (FDA). 13 June 2013. Archived from the original on 27 July 2019. Retrieved 15 March 2018.
  25. ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  26. ^ "Zolpidem Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Archived from the original on 1 September 2024. Retrieved 30 August 2024.