ZOLPIDEM TARTRATE
Clinical safety rating: safe
Animal studies have demonstrated safety
Zolpidem is a non-benzodiazepine hypnotic that binds selectively to the benzodiazepine-1 (BZ1) receptor subtype of the GABA-A receptor complex, potentiating GABAergic inhibition. This results in sedative, hypnotic, and anxiolytic effects.
| Metabolism | Hepatic metabolism primarily via CYP3A4, with minor contributions from CYP1A2 and CYP2C9. Metabolites are inactive. Clearance reduced in hepatic impairment. |
| Excretion | Renal (approximately 80% as metabolites, <1% unchanged), fecal (approximately 16%), biliary (minor). |
| Half-life | Terminal elimination half-life is approximately 2.5 hours (range 1.4–4.5 hours) in healthy adults; prolonged to about 2.9–4.5 hours in elderly and up to 9.9 hours in hepatic impairment. Clinical context: short half-life minimizes next-day sedation; accumulation unlikely with once-daily dosing. |
| Protein binding | Approximately 92–95% bound to serum albumin (primarily), with minor binding to α1-acid glycoprotein. |
| Volume of Distribution | 0.54 L/kg (range 0.4–0.8 L/kg) in adults. Clinical meaning: moderate distribution, consistent with lipophilic drug that readily crosses blood-brain barrier. |
| Bioavailability | Oral immediate-release: approximately 70% (range 67–72%) due to first-pass metabolism; sublingual: approximately 75% (higher relative to oral due to avoidance of first-pass); oral spray: approximately 70%; intravenous: 100%. |
| Onset of Action | Oral immediate-release: 15–30 minutes; sublingual: 10–20 minutes; oral spray: 10–20 minutes; intravenous: 1–3 minutes. |
| Duration of Action | Oral immediate-release: 3–4 hours (sleep maintenance variable); extended-release: longer sleep maintenance due to biphasic release; sublingual: ~3 hours; intravenous: ~2 hours. Clinical notes: duration sufficient for sleep initiation; extended-release may improve sleep maintenance; next-day effects possible if <7–8 hours sleep. |
10 mg orally once daily immediately before bedtime for adults; maximum dose 10 mg per day.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl <30 mL/min), consider reducing dose to 5 mg due to increased risk of sedation. |
| Liver impairment | For Child-Pugh class A or B: start with 5 mg. For Child-Pugh class C: not recommended due to lack of data and risk of encephalopathy. |
| Pediatric use | Not approved for use in pediatric patients (<18 years). Safety and efficacy not established. |
| Geriatric use | Initiate with 5 mg orally once daily immediately before bedtime; maximum 5 mg per day due to increased sensitivity and risk of falls and cognitive impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol increase sedation risk Can cause complex sleep behaviors like sleep-driving.
| Breastfeeding | Zolpidem is excreted into breast milk in low levels (M/P ratio estimated 0.13–0.33). Limited infant exposure; however, potential for sedation and impaired feeding in neonates. Caution advised; monitor infant for drowsiness and feeding difficulties. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: Use associated with fetal respiratory depression, hypotonia, and withdrawal symptoms in neonates; risk of floppy infant syndrome. Avoid in third trimester unless essential. |
■ FDA Black Box Warning
Complex sleep behaviors such as sleep-driving, making phone calls, preparing and eating food, or other activities while not fully awake, with amnesia for the event. Discontinue immediately if such behaviors occur.
| Common Effects | Dizziness |
| Serious Effects |
Hypersensitivity to zolpidem or any component; history of complex sleep behaviors; severe hepatic impairment (Child-Pugh C); concurrent use with alcohol or other CNS depressants.
| Precautions | CNS depression effects (impairs driving and hazardous activities); risk of dependence, abuse, and withdrawal; severe anaphylactic/anaphylactoid reactions; respiratory depression (caution in COPD or sleep apnea); worsening of depression or suicidal ideation; elderly patients at higher risk for falls and cognitive impairment. |
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| Fetal Monitoring | Monitor maternal vital signs and sedation level. In neonates exposed near term, observe for respiratory depression, hypotonia, and withdrawal symptoms for at least 48 hours postpartum. Consider umbilical cord blood levels if overdose suspected. |
| Fertility Effects | No specific human data on fertility impairment. Animal studies have not demonstrated significant reproductive toxicity at therapeutic doses. Theoretical risk of menstrual irregularities due to CNS effects. |