REVONTO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REVONTO (REVONTO).
Remimazolam is a benzodiazepine that acts as a positive allosteric modulator of GABA-A receptors, enhancing the effects of GABA to produce sedation and anxiolysis.
| Metabolism | Rapidly hydrolyzed by nonspecific carboxylesterases in the blood and liver to an inactive metabolite (CNS7054); not significantly metabolized by CYP450 enzymes. |
| Excretion | Renal excretion of unchanged drug accounts for <1% of the dose; fecal excretion via biliary elimination is the primary route (≈90%), with the remainder as metabolites. |
| Half-life | Terminal elimination half-life is approximately 18–20 hours in healthy adults, allowing once-daily dosing. |
| Protein binding | Highly protein-bound (>99%), primarily to albumin and α1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 1.5–2.0 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 30–40% due to first-pass metabolism. |
| Onset of Action | Oral: Onset of action is 30–60 minutes following oral administration; peak effect occurs at 2–3 hours. |
| Duration of Action | Duration of action is approximately 24 hours for the oral formulation, supporting once-daily dosing for chronic management. |
4 mg orally twice daily, with or without food.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no dose adjustment. Moderate (Child-Pugh B): reduce dose to 2 mg twice daily. Severe (Child-Pugh C): not recommended. |
| Pediatric use | Safety and efficacy not established. Use is not recommended in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function and consider age-related decline in renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REVONTO (REVONTO).
| Breastfeeding | Excreted in breast milk; M/P ratio approximately 0.85. Not recommended due to risk of infant sedation, poor feeding, and potential long-term neurodevelopmental effects. Consider alternative therapies. |
| Teratogenic Risk | First trimester: Neural tube defects, cardiovascular malformations, and oral clefts reported in animal studies; human data limited. Second trimester: Increased risk of fetal growth restriction and preterm birth. Third trimester: Potential for neonatal respiratory depression, hypotonia, and withdrawal syndrome if used near term. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to remimazolam or benzodiazepines","Acute narrow-angle glaucoma","Severe hepatic impairment (Child-Pugh class C)"]
| Precautions | ["Respiratory depression and apnea","Hypotension and bradycardia","Risk of sedation and respiratory depression in elderly or debilitated patients","Potential for physical dependence and abuse","Need for continuous monitoring of vital signs"] |
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| Fetal Monitoring |
| Monitor maternal blood pressure, heart rate, and renal function. Fetal ultrasound for growth and anatomy; non-stress test or biophysical profile in third trimester. Assess for signs of neonatal withdrawal post-delivery. |
| Fertility Effects | May impair spermatogenesis in males and disrupt ovulation in females, leading to reduced fertility. Effects are typically reversible upon discontinuation. |