Zolpidem
Zolpidem is a non-benzodiazepine hypnotic used in adults for the short-term treatment of insomnia. It selectively potentiates GABA-A receptors at the alpha-1 subunit, with a rapid onset and short half-life suited to sleep induction.
- Chemical formula
- C19H21N3O
- CAS number
- 82626-48-0
- ATC code
- N05CF02
- Molecular weight
- 307.39 g/mol
- Drug class
- Non-benzodiazepine hypnotic (Z-drug)
- Also known as
- SL 80.0750-23N, Zolpidem
What is it?
Zolpidem is an imidazopyridine compound first introduced in France in 1988 and now one of the most widely prescribed hypnotic medications. It is supplied as immediate-release tablets, controlled-release tablets, sublingual tablets and oral spray in different markets, and is dispensed only on prescription. Zolpidem is intended for short-term management of sleep-onset insomnia and for selected sleep maintenance issues with the controlled-release formulation.
Mechanism of action
Zolpidem is a positive allosteric modulator of the GABA-A receptor with relative selectivity for the alpha-1 subunit, which is associated with sedation and sleep induction. Compared with classic benzodiazepines, this profile theoretically minimises muscle relaxation, anxiolysis and amnesic effects, although in practice these can still occur. Increased chloride conductance hyperpolarises neurons in the central nervous system, particularly in cortical and thalamic regions related to sleep onset.
Pharmacokinetics
Zolpidem is rapidly absorbed after oral administration, with peak plasma concentrations reached within 30 to 90 minutes. Bioavailability is approximately 70%. Plasma protein binding is around 92%. The drug is metabolised in the liver mainly by CYP3A4 and CYP1A2 to inactive metabolites. The terminal half-life is approximately 2.5 hours, supporting use as a sleep-onset hypnotic with limited next-day residue. Hepatic impairment, age and concurrent CYP3A4 inhibitors increase exposure.
Indications
Zolpidem is approved in adults for the short-term treatment of insomnia, typically when difficulty falling asleep or maintaining sleep is associated with daytime impairment. According to international guidelines, prescription should be limited to two to four weeks, with periodic reassessment. Zolpidem is not indicated for chronic insomnia as a first-line approach when cognitive-behavioural therapy is available, nor for paediatric populations.
Safety profile
Common adverse effects include drowsiness, dizziness, headache and gastrointestinal symptoms. Complex sleep behaviours such as sleep-walking, sleep-eating and sleep-driving have been reported and represent a contraindication to continued use. Anterograde amnesia, falls in older adults and next-day impairment, particularly affecting driving, are documented. According to the prescribing information, the lowest effective dose should be used, especially in women and elderly patients, and concomitant alcohol or other CNS depressants should be avoided.
Products containing this ingredient
Frequently asked questions
How quickly does zolpidem work? ▾
Zolpidem typically begins to take effect within 15 to 30 minutes of an immediate-release tablet on an empty stomach, with peak plasma concentration reached at around 30 to 90 minutes. According to the prescribing information, the medication should be taken immediately before going to bed, with at least seven to eight hours of expected sleep time, to limit residual next-day sedation.
Are complex sleep behaviours common with zolpidem? ▾
Complex sleep behaviours such as sleep-walking, sleep-eating, telephoning or driving while not fully awake have been reported, mostly in patients also using alcohol, other CNS depressants or higher than recommended doses. Although uncommon, they can have serious consequences. According to the prescribing information and regulatory communications, any episode of complex sleep behaviour is a contraindication to continued zolpidem use.
Can zolpidem be taken every night long-term? ▾
Most clinical guidelines recommend short-term use of zolpidem, typically two to four weeks, because of the risk of tolerance, dependence, rebound insomnia and complex sleep behaviours. Longer use is sometimes considered in selected cases under specialist supervision and with periodic reassessment. According to the prescribing information, cognitive-behavioural therapy for insomnia is recommended as the first-line approach for chronic insomnia.
Why are zolpidem doses lower in women? ▾
Pharmacokinetic studies have shown that women clear zolpidem more slowly than men on average, leading to higher morning plasma concentrations and a greater risk of next-day driving impairment. For this reason, regulatory agencies recommend a lower starting dose in women than in men, and the prescribing information specifies sex-specific dosing for the immediate-release and controlled-release formulations.
What are the main contraindications for zolpidem? ▾
Zolpidem is contraindicated in known hypersensitivity to the molecule, in severe respiratory insufficiency, in obstructive sleep apnoea, in severe hepatic impairment and in patients with previous complex sleep behaviours. Caution is required in older adults, in patients with substance use disorders and during pregnancy and breastfeeding. According to the prescribing information, the medical history must be reviewed by a clinician before any prescription.
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