INTERMEZZO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INTERMEZZO (INTERMEZZO).
Gamma-hydroxybutyrate (GHB) is a CNS depressant that binds to GHB and GABA-B receptors, modulating dopamine and serotonin neurotransmission, and inducing slow-wave sleep.
| Metabolism | Primarily via GHB dehydrogenase to succinic semialdehyde; minor CYP450 involvement (not major). |
| Excretion | Renal excretion of conjugated metabolites accounts for approximately 80% of elimination, with fecal excretion of about 10% and minor biliary elimination. |
| Half-life | Terminal elimination half-life is approximately 1.5–3 hours; prolonged in elderly and patients with hepatic impairment, requiring dose adjustment. |
| Protein binding | Approximately 95–99% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.7–1.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Sublingual: approximately 75%; oral: approximately 85%. |
| Onset of Action | Sublingual: 10–20 minutes; oral: 30–45 minutes. |
| Duration of Action | Sublingual: 2–4 hours; oral: 3–6 hours, with residual sedation lasting up to 8 hours. |
| Molecular Weight | 356.4 |
1.75 mg or 3.5 mg sublingual tablet once nightly at bedtime. Do not take more than once per night and only if at least 7-8 hours of sleep time remain.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended; however, use with caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), reduce dose to 1.75 mg and use with caution. |
| Pediatric use | Not approved for use in pediatric patients (<18 years). Safety and efficacy not established. |
| Geriatric use | Elderly patients may be more sensitive to sedative effects. Recommended initial dose is 1.75 mg; avoid doses above 1.75 mg due to increased risk of falls and cognitive impairment. |
| 1st trimester | Insufficient human data; animal studies show risk. Avoid use during first trimester unless benefits outweigh risks. |
| 2nd trimester | Potential for fetal respiratory depression with prolonged use or high doses near term. Use only if clearly needed. |
| 3rd trimester | Prolonged use may lead to neonatal withdrawal syndrome. Avoid use, especially during late third trimester. |
Clinical note
Comprehensive clinical and safety monograph for INTERMEZZO (INTERMEZZO).
| Placental transfer | Crosses placenta rapidly; fetal concentrations similar to maternal. |
| Breastfeeding | Enters breast milk in low concentrations; monitor infant for excessive sedation and poor feeding. Use caution with repeated dosing. |
| Lactation Rating |
■ FDA Black Box Warning
WARNING: Central nervous system (CNS) depression and abuse potential. INTERMEZZO is a CNS depressant with abuse potential similar to alcohol. Concomitant use with alcohol or other CNS depressants may cause respiratory depression, hypotension, profound sedation, coma, or death.
| Serious Effects |
Hypersensitivity to zolpidem or any componentHistory of complex sleep behaviors (e.g., sleep-driving) with zolpidem
| Precautions | CNS depression, Respiratory depression, Abuse and dependence, Sleepwalking, Confusion, Depression and suicidality, Seizures, Use with other CNS depressants |
| Food/Dietary | Intermezzo may be taken with or without food. However, taking with a high-fat meal delays the absorption and reduces the peak concentration, potentially decreasing the hypnotic effect. Grapefruit juice may increase zolpidem levels; avoid concurrent consumption. Alcohol must be avoided as it potentiates CNS depression and increases risk of complex sleep behaviors. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: increased risk of oral clefts (case-control studies suggest OR 1.8-2.0). Second/third trimester: risk of fetal respiratory depression, hypotonia, withdrawal syndrome if used chronically or in high doses near term. Avoid use in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Maternal: vital signs, sedation level, respiratory rate. Fetal: nonstress test and biophysical profile if chronic use; ultrasound for growth if used in second/third trimester. Neonatal: observe for withdrawal symptoms (irritability, hypertonia, tremors) for 24-48 hours post-delivery. |
| Fertility Effects | No known direct effects on fertility. May affect menstrual cyclicity in chronic users due to hormonal alterations. Animal studies show no impairment of fertility at clinically relevant doses. |
| Clinical Pearls | Intermezzo (zolpidem tartrate) sublingual tablet is indicated for as-needed treatment of middle-of-the-night awakening with difficulty returning to sleep. Use only if there are at least 4 hours remaining before planned awakening. Due to rapid onset, patient must be in bed immediately after taking. Maximum dose is 1.75 mg for women and 3.5 mg for men per night. Do not exceed one dose per night. Concomitant use with alcohol or other CNS depressants increases risk of respiratory depression and severe sedation. Avoid in patients with history of complex sleep behaviors (e.g., sleep-driving). Use lowest effective dose; taper to discontinue if dependence suspected. |
| Patient Advice | Take Intermezzo only when you wake up in the middle of the night and have at least 4 hours of bedtime left. · Place the tablet under your tongue and allow it to dissolve completely; do not swallow or take with water. · Do not take more than one dose per night; do not use Intermezzo if you have already taken any other sleep medication. · Avoid alcohol and other sedatives while using Intermezzo, as this can cause dangerous drowsiness, slowed breathing, or unusual behaviors. · You may experience amnesia, confusion, hallucinations, or sleep-related activities like driving, eating, or making phone calls while not fully awake; stop use and contact your doctor if these occur. · Do not drive or operate machinery the morning after use, even if you feel alert. · Tell your doctor about all medications you take, especially opioids, other sedatives, antidepressants, or drugs for mental health conditions. |