PROSOM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROSOM (PROSOM).
GABAA receptor agonist, potentiates GABAergic inhibition
| Metabolism | Hepatic via CYP3A4 and glucuronidation |
| Excretion | Renal: 80% as metabolites, primarily conjugated; unchanged drug <1%. Fecal: 15%. Biliary: minor. |
| Half-life | Terminal elimination half-life is approximately 20–30 hours (mean 25 h) in adults. Clinically, this supports once-daily dosing with potential for accumulation with repeated administration. |
| Protein binding | 95% bound, primarily to albumin. |
| Volume of Distribution | 0.5–1.0 L/kg, indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral: 80–95% due to minimal first-pass metabolism. No other relevant routes. |
| Onset of Action | Oral: 30–60 minutes for sedation; sleep induction within 15–45 minutes. No parenteral route approved. |
| Duration of Action | 6–8 hours for hypnotic effect; residual sedation may persist for 10–12 hours, particularly in elderly or hepatic impairment. |
| Molecular Weight | 294.7 |
0.5 mg orally once daily at bedtime for insomnia; maximum dose 1 mg.
| Dosage form | TABLET |
| Renal impairment | No specific adjustment recommended; use with caution in severe renal impairment. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 0.25 mg; Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | Initiate at 0.25 mg orally once daily at bedtime; increase cautiously if needed to 0.5 mg. |
| 1st trimester | Estazolam is a benzodiazepine classified as pregnancy category X; teratogenic effects have been observed in animal studies and there is evidence of harm in human fetuses; use contraindicated in first trimester due to risk of congenital malformations. |
| 2nd trimester | Use contraindicated in second trimester; possible risks include low Apgar scores, respiratory depression, and hypotonia in neonates. |
| 3rd trimester | Use contraindicated in third trimester; high risk of neonatal withdrawal syndrome, floppy infant syndrome (hypotonia, sedation), and respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for PROSOM (PROSOM).
| Placental transfer | Crosses the placenta; drug and metabolites detected in cord blood; degree of transfer is moderate to high with lipid solubility facilitating passage. |
| Breastfeeding | Excreted into breast milk; may cause sedation, poor feeding, and weight loss in nursing infants; avoid breastfeeding due to potential accumulation and long half-life. |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancyBreastfeedingSevere hepatic impairmentMyasthenia gravisNarrow-angle glaucomaKnown hypersensitivity to estazolam or other benzodiazepines
| Precautions | Risk of dependence and withdrawal, CNS depression, Respiratory depression, Anterograde amnesia, Complex sleep-related behaviors |
| Food/Dietary | Avoid alcohol consumption while taking PROSOM due to additive CNS depression. Grapefruit juice may inhibit CYP3A4 metabolism and increase drug levels; limit or avoid grapefruit products. High-fat meals may delay absorption, but clinical significance is minimal. No other specific food restrictions. |
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| Lactation Rating | L4 (Hazardous) |
| Teratogenic Risk | Pregnancy Category X. Estazolam is contraindicated in pregnancy due to benzodiazepine class effects. First trimester: increased risk of congenital malformations (cleft lip/palate, cardiac defects). Second/third trimesters: risk of fetal benzodiazepine syndrome, including hypotonia, respiratory depression, withdrawal symptoms. Neonatal effects: floppy infant syndrome, sedation, withdrawal seizures. |
| Fetal Monitoring | Monitor maternal sedation, respiratory rate, and signs of dependence. Fetal monitoring: assess fetal growth and development via ultrasound, monitor for neonatal withdrawal after delivery. No specific routine monitoring required beyond standard prenatal care if accidental exposure occurs. |
| Fertility Effects | No specific data on estazolam effects on fertility. Benzodiazepines may alter menstrual cyclicity or spermatogenesis at high doses based on animal studies. Clinically relevant effects are unlikely at therapeutic doses. |
| Clinical Pearls |
| PROSOM (estazolam) is a triazolobenzodiazepine with an intermediate half-life (10-24 hours). For insomnia, start at 1 mg at bedtime in elderly or debilitated patients due to increased sensitivity; usual adult dose is 2 mg. Avoid in severe hepatic impairment and sleep apnea. Rebound insomnia may occur upon abrupt discontinuation. Monitor for tolerance, dependence, and complex sleep-related behaviors (e.g., sleep-driving). Coadministration with CYP3A4 inhibitors (e.g., ketoconazole) increases levels; use with CNS depressants (e.g., alcohol) increases sedation. |
| Patient Advice | Take PROSOM exactly as prescribed, just before bedtime for sleep initiation. · Do not take if you have consumed alcohol or other CNS depressants; may cause dangerous sedation. · Avoid driving or operating machinery until you know how the drug affects you, especially the next day. · Do not share this medication; it can be habit-forming and has abuse potential. · Inform your doctor of all medications, including OTC and herbal supplements (e.g., St. John's wort). · Do not stop suddenly; tapering is needed to avoid withdrawal symptoms (anxiety, insomnia, seizures). · Report any unusual sleep behaviors (sleepwalking, driving while not fully awake). · Store at room temperature, away from moisture and light. |