Description

Simple

A sleep medication used for short period of time to help with falling asleep.

Clinical

A sedative hypnotic used for the short-term treatment of insomnia to improve sleep latency.

Overview

Zolpidem, also known as _Ambien_, is a hypnotic drug that was initially approved by the FDA in 1992 [FDA label]. Zolpidem improves sleep in patients with insomnia. It is aimed for use in patients with difficulties initiating sleep. This drug decreases the time to fall asleep (sleep latency), increases the duration of sleep, and decreases the number of awakenings during sleep in patients with temporary (transient) insomnia. It is available in both immediate acting and extended release forms [FDA label], [17].

Its tolerability profile is favorable when administered according to the manufacturer’s instructions, with a low risk of drug withdrawal, drug dependence, and drug tolerance [6]. In addition, zolpidem improves sleep quality in patients suffering from chronic insomnia and can show mild muscle relaxant properties [15]. Research also shows that zolpidem is rapid and effective in restoring brain function for patients in a vegetative state following brain injury. This drug has the propensity to completely or partially reverse the abnormal metabolism of damaged... Read more

Pharmacology

Indication

This drug is indicated for the short-term treatment of insomnia in adults characterized by difficulties with sleep initiation [FDA label].

Pharmacodynamic

**Effects on the central nervous system (CNS)**

This drug has CNS depressant effects, which may include somnolence, decreased alertness, sedation, drowsiness, dizziness, and other changes in psychomotor function [FDA label]. Due to the above effects, the FDA has recommended an initial dose of z... Read more

Mechanism of action


Zolpidem, the active moiety of zolpidem tartrate, is a hypnotic substance with a chemical structure that is not related to the structure benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines or other drugs exerting hypnotic effects. It interacts with a _GABA-BZ_ receptor complex and... Read more

Absorption

Zolpidem is rapidly absorbed from the gastrointestinal tract. In a single-dose crossover study in 45 healthy subjects given 5 and 10 mg zolpidem tartrate tablets, the average peak zolpidem concentrations (Cmax) were 59 and 121 ng/mL, respectively, occurring at a mean time (Tmax) of 1.6 hours for bot... Read more

Protein binding

92.5 ± 0.1% [FDA label]

Volume of distribution

0.54 to 0.68 L/kg (in humans) [7]. In patients with... Read more

Clearance

In a clinical trial, after a 20mg dose, total clearance of zolpidem 0.24 to 0.27 ml/min/kg [ Read more

Half life

The average zolpidem elimination half-life was 2.6 and 2.5 hours, for the 5 and 10 mg tablets, respectively [FDA label].

Route of elimination

Zolpidem tartrate tablets are converted to inactive metabolites that are eliminated mainly by renal excretion [FDA label].

Toxicity

Oral (male rat) LD50 = 695 mg/kg [MSDS].

**Overdose**

Symptoms of overdose include impairment of consciousness ranging from somnolence to light coma, in addition to cardiorespiratory collapse resulting in fatal outcomes have been reported [FDA label].

**Withdrawal effects**

F... Read more

Adverse Effects

Contraindications

  • Regions: US
  • Patient Conditions:
      • Name: Known hypersensitivity to zolpidem
      • Drugbank Id: DBCOND0117988

Food Interactions

  • Avoid alcohol.
  • Should not be administered with or immediately after a meal.

Interactions

Type in a drug name to check for interaction with Zolpidem
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be decreased when combined with Zolpidem.
(S)-Warfarin
The metabolism of (S)-Warfarin can be decreased when combined with Zolpidem.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Zolpidem can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
2,5-Dimethoxy-4-ethylthioamphetamine
2,5-Dimethoxy-4-ethylthioamphetamine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
4-Bromo-2,5-dimethoxyamphetamine
4-Bromo-2,5-dimethoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
4-Methoxyamphetamine
4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
5-methoxy-N,N-dimethyltryptamine
5-methoxy-N,N-dimethyltryptamine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
6-Deoxyerythronolide B
The metabolism of Zolpidem can be decreased when combined with 6-Deoxyerythronolide B.
7-ethyl-10-hydroxycamptothecin
The metabolism of Zolpidem can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
7-Nitroindazole
7-Nitroindazole may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
8-azaguanine
The metabolism of 8-azaguanine can be decreased when combined with Zolpidem.
8-chlorotheophylline
The metabolism of 8-chlorotheophylline can be decreased when combined with Zolpidem.
9-aminocamptothecin
The metabolism of Zolpidem can be decreased when combined with 9-aminocamptothecin.
9-Deazaguanine
The metabolism of 9-Deazaguanine can be decreased when combined with Zolpidem.
9-Methylguanine
The metabolism of 9-Methylguanine can be decreased when combined with Zolpidem.
Abatacept
The metabolism of Zolpidem can be increased when combined with Abatacept.
Abiraterone
The serum concentration of Zolpidem can be increased when it is combined with Abiraterone.
Acalabrutinib
The metabolism of Zolpidem can be decreased when combined with Acalabrutinib.
Acebutolol
The metabolism of Zolpidem can be decreased when combined with Acebutolol.
17 References
  1. 1 . Lemmer B: The sleep-wake cycle and sleeping pills. Physiol Behav. 2007 Feb 28;90(2-3):285-93. Epub 2006 Oct 16.PubMed: 17049955
  2. 2 . Depoortere H, Zivkovic B, Lloyd KG, Sanger DJ, Perrault G, Langer SZ, Bartholini G: Zolpidem, a novel nonbenzodiazepine hypnotic. I. Neuropharmacological and behavioral effects. J Pharmacol Exp Ther. 1986 May;237(2):649-58.PubMed: 2871178
  3. 3 . Clauss RP, Guldenpfennig WM, Nel HW, Sathekge MM, Venkannagari RR: Extraordinary arousal from semi-comatose state on zolpidem. A case report. S Afr Med J. 2000 Jan;90(1):68-72.PubMed: 10721397
  4. 4 . Schlich D, L'Heritier C, Coquelin JP, Attali P, Kryrein HJ: Long-term treatment of insomnia with zolpidem: a multicentre general practitioner study of 107 patients. J Int Med Res. 1991 May-Jun;19(3):271-9.PubMed: 1670039
  5. 5 . Maarek L, Cramer P, Attali P, Coquelin JP, Morselli PL: The safety and efficacy of zolpidem in insomniac patients: a long-term open study in general practice. J Int Med Res. 1992 Apr;20(2):162-70.PubMed: 1521672
  6. 6 . Swainston Harrison T, Keating GM: Zolpidem: a review of its use in the management of insomnia. CNS Drugs. 2005;19(1):65-89. doi: 10.2165/00023210-200519010-00008.PubMed: 15651908
  7. 7 . Salva P, Costa J: Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clin Pharmacokinet. 1995 Sep;29(3):142-53. doi: 10.2165/00003088-199529030-00002.PubMed: 8521677
  8. 8 . Fitzgerald AC, Wright BT, Heldt SA: The behavioral pharmacology of zolpidem: evidence for the functional significance of alpha1-containing GABA(A) receptors. Psychopharmacology (Berl). 2014 May;231(9):1865-96. doi: 10.1007/s00213-014-3457-x. Epub 2014 Feb 22.PubMed: 24563183
  9. 9 . Du B, Shan A, Zhang Y, Zhong X, Chen D, Cai K: Zolpidem arouses patients in vegetative state after brain injury: quantitative evaluation and indications. Am J Med Sci. 2014 Mar;347(3):178-82. doi: 10.1097/MAJ.0b013e318287c79c.PubMed: 23462249
  10. 10 . Guo T, Mao G, Zhao L, Xia D, Yang L: Comparative pharmacokinetics of zolpidem tartrate in five ethnic populations of China. Acta Pharm Sin B. 2014 Apr;4(2):146-50. doi: 10.1016/j.apsb.2014.02.001. Epub 2014 Mar 15.PubMed: 26579377
  11. 11 . Tan KR, Rudolph U, Luscher C: Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends Neurosci. 2011 Apr;34(4):188-97. doi: 10.1016/j.tins.2011.01.004. Epub 2011 Feb 25.PubMed: 21353710
  12. 12 . Vlainic J, Pericic D: Effects of acute and repeated zolpidem treatment on pentylenetetrazole-induced seizure threshold and on locomotor activity: comparison with diazepam. Neuropharmacology. 2009 Jun;56(8):1124-30. doi: 10.1016/j.neuropharm.2009.03.010. Epub 2009 Apr 1.PubMed: 19345234
  13. 13 . Crestani F, Martin JR, Mohler H, Rudolph U: Mechanism of action of the hypnotic zolpidem in vivo. Br J Pharmacol. 2000 Dec;131(7):1251-4. doi: 10.1038/sj.bjp.0703717.PubMed: 11090095
  14. 14 . FDA Drug Safety Communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR Link
  15. 15 . NIH Stat Pearls, Internet: Zolpidem Link
  16. 16 . Questions and Answers: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist) Link
  17. 17 . Ambien CR (extended release) label File