REVONTO
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 410.5 |
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 | Avoid due to risk of fetal harm; animal studies show adverse effects and no adequate human data. |
| 2nd trimester | Avoid; potential for fetal hypotension and intrauterine growth restriction. |
| 3rd trimester | Avoid; may cause premature closure of ductus arteriosus and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for REVONTO (REVONTO).
| Placental transfer | Crosses placenta; detected in fetal plasma at concentrations similar to maternal. |
| Breastfeeding | Excreted in human milk in small amounts; no reports of adverse effects in infants. Caution with premature infants or renal impairment. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to endothelin receptor antagonistsSevere hepatic impairment (Child-Pugh class C)Pregnancy
| 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 |
| Food/Dietary | Avoid high-fat meals as they can significantly increase drug absorption and risk of adverse effects. Grapefruit and grapefruit juice should be avoided due to potential CYP3A4 inhibition affecting metabolism. Limit caffeine intake as combination may exacerbate side effects like anxiety and palpitations. |
| Clinical Pearls | REVONTO is a proprietary formulation not recognized in standard medical literature. Verify with pharmacist for active ingredient(s) and dosing. If it contains naltrexone-bupropion combination (brand name Contrave), use with caution in patients with seizure history or eating disorders. Monitor blood pressure regularly due to possible hypertensive effects. Contraindicated with concomitant MAOIs or during abrupt opioid withdrawal. |
| Patient Advice | Take with a low-fat meal to reduce gastrointestinal side effects and improve tolerability. · Avoid alcoholic beverages as they may increase the risk of seizures and hepatotoxicity. · Report any signs of allergic reaction (rash, itching, swelling) or mood changes immediately. · Do not discontinue abruptly; taper under medical supervision to avoid withdrawal symptoms. · Store at room temperature away from moisture and heat. |
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