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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INTERMEZZO (INTERMEZZO).
| Breastfeeding | Enters breast milk. M/P ratio approximately 0.66. Relative infant dose ~2-3% of weight-adjusted maternal dose. Monitor infant for sedation, poor feeding. Use with caution; consider alternative if infant has respiratory compromise. |
| 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. |
■ 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 GHB or any component","Treatment with alcohol or other CNS depressants","Succinic semialdehyde dehydrogenase deficiency"]
| Precautions | ["CNS depression","Respiratory depression","Abuse and dependence","Sleepwalking","Confusion","Depression and suicidality","Seizures","Use with other CNS depressants"] |
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| 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. |