Zolpidem

Non-benzodiazepine hypnotic (Z-drug), imidazopyridine

ATC code: N05CF02

Brand names: Ambien, Ambien CR, Intermezzo, Edluar

Updated 24 Sep 2026 · Methodology

Indications

Insomnia and sleep disorders

Second line

Zolpidem is a non-benzodiazepine Z-hypnotic. AEMPS authorises it for insomnia in short courses up to 4 weeks, including the taper. SEN 2022 and 2021 place cognitive-behavioural therapy for insomnia (CBT-I) first; pharmacotherapy (zolpidem, eszopiclone, prolonged-release melatonin) is second-line when CBT-I fails or is unfeasible. Cochrane 2018 shows Z-drugs shorten sleep onset by 18–22 minutes – clinically modest. Long-term use leads to tolerance and dependence. The marketing position of «a safe alternative to benzodiazepines» does not match the regulatory stance: and added warnings about parasomnias and complex sleep behaviours. If zolpidem was prescribed without discussion of CBT-I, consider seeking a second opinion.

Sources

ICD-10: G47.0 · ICD-11: 7A00

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Jet lag disorder

Not recommended

Zolpidem is sometimes prescribed for jet lag «to help fall asleep in the new time zone». AEMPS does not authorise this indication. Zolpidem has a short half-life and helps sleep onset but does not shift the circadian rhythm – sleep architecture does not normalise the next day. For jet lag, 2020 recommends melatonin 0.5–5 mg 30 minutes before the desired sleep (stronger evidence) and behavioural strategies (morning light in the new time zone, avoiding caffeine and alcohol on the flight). Zolpidem use on planes is associated with complex sleep behaviours (walking, eating without recall). If zolpidem was prescribed solely for jet lag, consider seeking a second opinion.

Sources

ICD-10: G47.25 · ICD-11: 7A65

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Selective agonist of the benzodiazepine site of the GABA-A receptor with preference for the α1 subunit. Enhances GABAergic inhibition and shortens sleep onset latency. The α1 selectivity explains the predominantly hypnotic effect and minimal muscle-relaxant and anticonvulsant effects compared with classical benzodiazepines. Rapid onset (15–30 minutes), short half-life (2–3 hours) – suitable for sleep-onset insomnia, less so for early-morning awakenings. Metabolised via CYP3A4 (75%) and CYP1A2.

Safety

Contraindications

Hypersensitivity to zolpidem
Severe respiratory failure
Sleep apnoea syndrome
Severe hepatic impairment
Myasthenia gravis
Age under 18 years
Acute alcohol or opioid intoxication

Serious adverse effects

Complex sleep behaviours: sleepwalking, sleep-driving, sleep-eating without recall
Anterograde amnesia
Paradoxical reactions (agitation, aggression, hallucinations)
Dependence and withdrawal syndrome on abrupt discontinuation
Falls and fractures in older adults
Respiratory depression when combined with opioids or alcohol

Common adverse effects

Next-day drowsiness
Headache
Dizziness
Confusion and memory impairment
Nausea
Dry mouth

Pregnancy: can you take Zolpidem?

AEMPS summary of product characteristics (section 4.6): zolpidem is not recommended during pregnancy, especially in the first trimester, and treatment is withdrawn if a woman plans a pregnancy or finds out she is pregnant. There are no or limited data on zolpidem in pregnant women; it crosses the placenta, and animal studies do not suggest reproductive toxicity. Cohort data on benzodiazepines and benzodiazepine-like drugs (more than 1,000 pregnancy outcomes) show no malformations after first-trimester exposure, although some case-control studies reported more cleft lip and palate. Reduced fetal movement and changes in fetal heart rate variability have been described after use in the second or third trimester, and use late in pregnancy or during labour has been linked to neonatal hypothermia, hypotonia, feeding difficulties (floppy infant syndrome) and respiratory depression, sometimes severe. Infants of mothers who took such drugs regularly late in pregnancy may develop withdrawal symptoms after birth, so newborns should be monitored.

Breastfeeding: can you take Zolpidem?

Compatible in short courses. Hale L3. Transfers into milk in small amounts (under 0.02% of maternal dose). Long-term use can cause infant sedation and poor feeding. eLactancia – «low risk» for single doses. Take after the evening feed.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Drug–drug interactions

1 pair found. Sorted from critical to minor.

ModerateDarunavirSecond-generation HIV protease inhibitor

Mechanism

Hepatic enzymes clear zolpidem, mainly CYP3A4 with a contribution from CYP1A2. Darunavir is always given with a booster, ritonavir or cobicistat, and the boosted combination strongly inhibits CYP3A4, so zolpidem concentration rises. The darunavir label lists zolpidem among sedatives/hypnotics that are 'extensively metabolised by CYP3A' and warns that their concentration may rise substantially. The pair itself was not studied. The zolpidem label confirms the direction: ketoconazole, a potent CYP3A4 inhibitor, raised zolpidem exposure 1.83-fold, prolonged its half-life and increased sedation. Zolpidem is not among the hypnotics contraindicated with darunavir; that list contains only triazolam and oral midazolam.

Symptoms

Expect a stronger and longer zolpidem effect: deeper drowsiness, slowed reactions, impaired attention and coordination, including the next morning and while driving. The risk of falls, confusion, amnesia and complex sleep behaviours rises: sleep-walking, sleep-driving, eating or phone calls with no memory of them. Alcohol, opioids and other central nervous system (CNS) depressants add to the sedation, and with opioids the risk of respiratory depression grows.

Management

The combination is not banned. Among hypnotics, only triazolam and oral midazolam are contraindicated with darunavir, and zolpidem is not on that list (darunavir label, , 4.3). The EMA label recommends clinical monitoring and asks to consider a lower zolpidem dose (darunavir label, EMA, 4.5). The label says the same: titration, a lower dose and monitoring for adverse events (darunavir label FDA, 7). The documents name no specific reduced dose. The zolpidem label has two doses: the usual 10 mg, and 5 mg for elderly or debilitated patients and in hepatic impairment, with a ceiling of 10 mg per night (zolpidem label, 4.2). It does not require a systematic dose reduction with potent CYP3A4 inhibitors but asks to warn the patient about stronger sedation (zolpidem label, 4.5); the FDA label suggests considering a lower zolpidem dose (zolpidem label FDA, 7.2). Zolpidem is taken once, right before bedtime, with no repeat dose the same night, and at least 8 hours should pass before driving or other work that needs alertness (zolpidem label, 4.4). Alcohol and other central nervous system (CNS) depressants are avoided; with opioids the dose and duration are limited (zolpidem label, 4.4 and 4.5). Complex sleep behaviours such as sleep-walking, sleep-driving or eating with no memory of it mean zolpidem is stopped at once (zolpidem label, 4.4). The zolpidem course is kept short: a few days to two weeks, four weeks at most including tapering (zolpidem label, 4.2).

Sources

Pair details →Darunavir →

Label mentions37 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorCiprofloxacin
«Inductores e inhibidores del CYP450: La administración concomitante de ciprofloxacino puede aumentar las concentraciones plasmáticas de zolpidem, por lo que no se recomienda su uso combinado.»
AEMPS, section 4.5 · Open on CIMA
MajorFluvoxamine
«La administración concomitante de fluvoxamina puede aumentar las concentraciones plasmáticas de zolpidem, por lo que no se recomienda su uso combinado.»
AEMPS, section 4.5 · Open on CIMA
MajorKetoconazole
«Drugs that Affect Drug Metabolism via Cytochrome P450: Ketoconazole, a potent CYP3A4 inhibitor, increased the exposure to and pharmacodynamic effects of zolpidem. Consideration should be given to…»
FDA, section 7 · Open on DailyMed
Majoropioidesclass named in the label
«Riegos de la administración concomitante con opioides: Se debe monitorizar cuidadosamente a los pacientes en busca de signos y síntomas de depresión respiratoria y sedación. A este respecto, se…»
AEMPS, section 4.4 · Open on CIMA
Majoropioidsclass named in the label
«CNS-Active Drugs: Opioids The concomitant use of Zolpidem tartrate tablets with opioids may increase the risk of respiratory depression. Limit dosage and duration of concomitant use of Zolpidem…»
FDA, section 7 · Open on DailyMed
ModerateCYP3A4 inducersclass named in the label
«Drugs that Affect Drug Metabolism via Cytochrome P450: Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem. Use of Rifampin in combination…»
FDA, section 7 · Open on DailyMed
ModerateCYP3A4 inhibitorsclass named in the label
«Drugs that Affect Drug Metabolism via Cytochrome P450: Ketoconazole, a potent CYP3A4 inhibitor, increased the exposure to and pharmacodynamic effects of zolpidem. Consideration should be given to…»
FDA, section 7 · Open on DailyMed
ModerateKetoconazole
«Inductores e inhibidores del CYP450: La administración concomitante de zolpidem y ketoconazol, que es un potente inhibidor de la CYP3A4, prolonga la vida media de zolpidem. La exposición total de…»
AEMPS, section 4.5 · Open on CIMA
antiepilépticosclass named in the label
«Depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor central al administrar concomitantemente antipsicóticos (neurolépticos), hipnóticos…»
AEMPS, section 4.5 · Open on CIMA
antihistamínicosclass named in the label
«Depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor central al administrar concomitantemente antipsicóticos (neurolépticos), hipnóticos…»
AEMPS, section 4.5 · Open on CIMA
antipsicóticosclass named in the label
«Depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor central al administrar concomitantemente antipsicóticos (neurolépticos), hipnóticos…»
AEMPS, section 4.5 · Open on CIMA
Bupropion
«Depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor central al administrar concomitantemente antipsicóticos (neurolépticos), hipnóticos…»
AEMPS, section 4.5 · Open on CIMA
Carbamazepine
«Inductores e inhibidores del CYP450: La rifampicina induce el metabolismo de zolpidem, resultando en una reducción de aproximadamente un 60 % de la concentración plasmática máxima y posiblemente una…»
AEMPS, section 4.5 · Open on CIMA
Chlorpromazine
«Otros fármacos: Cuando se administró zolpidem con warfarina, haloperidol, clorpromazina, digoxina o ranitidina, no se observaron interacciones farmacocinéticas significativas.»
AEMPS, section 4.5 · Open on CIMA
Chlorpromazine
«DRUG INTERACTIONS: Chlorpromazine: Impaired alertness and psychomotor performance observed ( 7.1 )»
FDA, section 7 · Open on DailyMed
Digoxin
«Otros fármacos: Cuando se administró zolpidem con warfarina, haloperidol, clorpromazina, digoxina o ranitidina, no se observaron interacciones farmacocinéticas significativas.»
AEMPS, section 4.5 · Open on CIMA
Fluoxetine
«Depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor central al administrar concomitantemente antipsicóticos (neurolépticos), hipnóticos…»
AEMPS, section 4.5 · Open on CIMA
Fluoxetine
«CNS-Active Drugs: Fluoxetine»
FDA, section 7 · Open on DailyMed
Haloperidol
«Otros fármacos: Cuando se administró zolpidem con warfarina, haloperidol, clorpromazina, digoxina o ranitidina, no se observaron interacciones farmacocinéticas significativas.»
AEMPS, section 4.5 · Open on CIMA
Haloperidol
«CNS-Active Drugs: Haloperidol»
FDA, section 7 · Open on DailyMed
Itraconazole
«Inductores e inhibidores del CYP450: Los compuestos que inhiben los enzimas hepáticos (en particular el CYP3A4) pueden aumentar las concentraciones plasmáticas y potenciar la actividad de zolpidem…»
AEMPS, section 4.5 · Open on CIMA
Phenytoin
«Inductores e inhibidores del CYP450: La rifampicina induce el metabolismo de zolpidem, resultando en una reducción de aproximadamente un 60 % de la concentración plasmática máxima y posiblemente una…»
AEMPS, section 4.5 · Open on CIMA
relajantes muscularesclass named in the label
«Depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor central al administrar concomitantemente antipsicóticos (neurolépticos), hipnóticos…»
AEMPS, section 4.5 · Open on CIMA
Rifampicin
«Inductores e inhibidores del CYP450: La rifampicina induce el metabolismo de zolpidem, resultando en una reducción de aproximadamente un 60 % de la concentración plasmática máxima y posiblemente una…»
AEMPS, section 4.5 · Open on CIMA
Sertraline
«Depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor central al administrar concomitantemente antipsicóticos (neurolépticos), hipnóticos…»
AEMPS, section 4.5 · Open on CIMA
Sertraline
«CNS-Active Drugs: Sertraline»
FDA, section 7 · Open on DailyMed
Venlafaxine
«Depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor central al administrar concomitantemente antipsicóticos (neurolépticos), hipnóticos…»
AEMPS, section 4.5 · Open on CIMA
Warfarin
«Otros fármacos: Cuando se administró zolpidem con warfarina, haloperidol, clorpromazina, digoxina o ranitidina, no se observaron interacciones farmacocinéticas significativas.»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

MajorCiprofloxacin
«Zolpidem: La administración concomitante con ciprofloxacino puede aumentar los niveles sanguíneos de zolpidem, no se recomienda el uso concomitante.»
AEMPS, section 4.5 · Open on CIMA
MajorCiprofloxacin
«DRUG INTERACTIONS: Zolpidem Avoid Use Co-administration with ciprofloxacin may increase blood levels of zolpidem, concurrent use is not recommended»
FDA, section 7 · Open on DailyMed
MajorCobicistat
«Established and Other Potentially Significant Interactions: buspirone zolpidem With other sedatives/hypnotics that are CYP3A metabolized, dose reduction may be necessary and clinical monitoring is…»
FDA, section 7 · Open on DailyMed
ModerateDarunavir
«SEDANTES/HIPNÓTICOS: Buspirona Clorazepato Diazepam Estazolam Flurazepam Midazolam (parenteral) Zolpidem Midazolam (oral) Triazolam»
AEMPS, section 4.5 · Open on CIMA
ModerateDarunavir
«Established and Other Potentially Significant Drug Interactions: Sedatives/hypnotics: orally administered midazolam, triazolam metabolized by CYP3A e.g. buspirone, diazepam, estazolam, zolpidem…»
FDA, section 7 · Open on DailyMed
ModerateRitonavir
«Inductores del sueño: Zolpidem y ritonavir pueden co-administrarse con una monitorización cuidadosa, de un excesivo efecto sedante.»
AEMPS, section 4.5 · Open on CIMA
ModerateRitonavir
«Established and Other Potentially Significant Drug Interactions: Sedative/Hypnotics: buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem ↑ sedative/hypnotics A dose decrease may be…»
FDA, section 7 · Open on DailyMed
Melatonin
«Melatonina puede potenciar las propiedades sedantes de las benzodiacepinas y de los hipnóticos no benzodiacepínicos, tales como el zaleplón, el zolpidem y la zopiclona. En un ensayo clínico se…»
AEMPS, section 4.5 · Open on CIMA
Rifampicin
«ansiolíticos e hipnóticos (p. ej., diazepam, benzodiazepinas, zolpicolona, zolpidem),»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Zolpidem used for?

Zolpidem is evaluated for the following indications with varying evidence strength: Insomnia and sleep disorders (evidence tier B), Jet lag disorder (evidence tier D). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Zolpidem?

Common side effects of Zolpidem (≥ 1 in 100): Next-day drowsiness, Headache, Dizziness, Confusion and memory impairment, Nausea, Dry mouth. See the Safety section for uncommon and serious reactions.

Is Zolpidem safe during pregnancy?

Is Zolpidem compatible with breastfeeding?

Who should not take Zolpidem?

Zolpidem is contraindicated in: Hypersensitivity to zolpidem; Severe respiratory failure; Sleep apnoea syndrome; Severe hepatic impairment; Myasthenia gravis. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 10/21/2024
FDA / DailyMedLabel dated 09/01/2026

Other drugs in this group

Alprazolam, Amisulpride, Apigenin, Aripiprazole, Chamomile (Matricaria chamomilla / recutita, flowers), Fabomotizole, Melatonin, Pimavanserin