VERSED
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VERSED (VERSED).
Benzodiazepine that enhances GABA-A receptor activity, increasing chloride ion conductance and causing neuronal hyperpolarization.
| Metabolism | Hepatic via CYP3A4 isoenzymes; major metabolites include midazolam glucuronide (inactive) and alpha-hydroxymidazolam (active). |
| Excretion | Renal: ~1% unchanged; Hepatic metabolism to glucuronide conjugates and 1-hydroxymidazolam, with subsequent renal elimination of metabolites. Fecal excretion is minimal (<2%). |
| Half-life | Terminal elimination half-life: 1.8–2.5 hours in healthy adults; prolonged in elderly (up to 6 hours), obesity (up to 8 hours), hepatic cirrhosis (up to 20 hours), and critically ill patients. |
| Protein binding | 97% bound primarily to albumin. |
| Volume of Distribution | 1–1.5 L/kg (0.5–1.2 L/kg in adults); increased in obesity and hepatic disease, indicating extensive tissue distribution. |
| Bioavailability | IM: 90%±; Oral: 40–50% (range 30–70%); Intranasal: ~75%; Rectal: ~50%. |
| Onset of Action | IV: 1–2 minutes; IM: 15 minutes; Oral: 15–30 minutes; Intranasal: 10–15 minutes; Rectal: 10–20 minutes. |
| Duration of Action | IV: 20–30 minutes (amnesia persists up to 1–2 hours); IM: 30–60 minutes; Oral: 1–2 hours; effects may be prolonged in elderly and hepatic impairment. |
| Molecular Weight | 325.77 |
IV: Initial 1-2.5 mg; titrate by 0.5-1 mg every 2-3 min; usual total 2.5-5 mg for sedation. IM: 0.07-0.08 mg/kg (max 5 mg) once. Oral: 7.5-15 mg once (preoperative).
| Dosage form | INJECTABLE |
| Renal impairment | eGFR 10-50 mL/min: No dose adjustment needed but monitor for prolonged sedation. eGFR <10 mL/min: Consider 50% dose reduction and monitor closely. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Avoid use or reduce dose by 75%. |
| Pediatric use | Neonates: IV 0.05-0.1 mg/kg; max 0.15 mg/kg. Children: IV 0.025-0.05 mg/kg (max 2 mg); titrate. Oral 0.25-0.5 mg/kg (max 20 mg) for sedation. IM 0.07-0.08 mg/kg. |
| Geriatric use | IV: Initial 0.5-1 mg over 2 minutes; titrate slowly; max total dose 3.5 mg. Oral: 5 mg preoperatively. Reduced clearance necessitates careful titration. |
| 1st trimester | Avoid unless clearly needed. Midazolam crosses placenta; fetal malformations reported in some studies, but risk not definitively established. |
| 2nd trimester | Use only if benefit outweighs risk. May cause fetal respiratory depression and hypotonia with prolonged use. |
| 3rd trimester | Avoid near term and during labor. Neonatal withdrawal and floppy infant syndrome reported. Use in labor may cause respiratory depression in newborn. |
Clinical note
Comprehensive clinical and safety monograph for VERSED (VERSED).
| Placental transfer | Midazolam rapidly crosses the placenta with fetal plasma concentrations reaching 50-80% of maternal levels. |
| Breastfeeding | Midazolam enters breast milk in low concentrations; however, due to potential for sedation in the infant, caution is advised. Monitor infant for drowsiness, poor feeding, and respiratory depression. |
■ FDA Black Box Warning
Intravenous administration may cause respiratory depression and arrest, especially when used with opioids. Resuscitation equipment and skilled personnel must be available. Do not administer by rapid bolus injection.
| Serious Effects |
Acute narrow-angle glaucomaKnown hypersensitivity to midazolam or any benzodiazepineSevere respiratory insufficiencyMyasthenia gravis
| Precautions | Respiratory depression, hypotension, paradoxical reactions, dependence and withdrawal, use in elderly or debilitated patients, hepatic/renal impairment, myasthenia gravis, glaucoma, pregnancy (category D). |
| Food/Dietary | Grapefruit juice inhibits CYP3A4 and can significantly increase midazolam plasma concentrations, prolonging sedation and respiratory depression. Avoid grapefruit products for at least 24 hours before and after administration. High-fat meals may reduce absorption rate but not extent, though clinical significance is minimal. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Midazolam is classified as FDA Pregnancy Category D. There is evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans. First trimester exposure may be associated with an increased risk of congenital malformations (e.g., cleft palate). Second and third trimester exposure may cause fetal CNS depression, respiratory depression, and withdrawal symptoms (floppy infant syndrome). Use during labor may cause neonatal respiratory depression and hypotonia. Maternal hypotension and decreased uterine blood flow may occur. |
| Fetal Monitoring | Continuous maternal monitoring of vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation) is required during administration. Fetal heart rate monitoring is recommended during use near term or during labor. Neonatal monitoring for respiratory depression, hypotonia, and withdrawal symptoms is essential if used near delivery. Assess maternal level of sedation and ability to maintain airway patency. |
| Fertility Effects | Midazolam has no well-documented adverse effects on human fertility. Animal studies have shown no impairment of fertility at clinically relevant doses. However, chronic use may cause menstrual irregularities or hormonal disturbances due to effects on gonadotropin-releasing hormone and cortisol metabolism. |
| Clinical Pearls | Midazolam (Versed) is a short-acting benzodiazepine used for procedural sedation, pre-anesthetic medication, and status epilepticus. It has amnestic properties. Onset is rapid (1-2 min IV, 15-30 min IM). Flumazenil is the reversal agent. Caution in elderly, hepatic impairment, and respiratory compromise. CYP3A4 inhibitors (e.g., macrolides, azole antifungals, grapefruit juice) increase levels. Not recommended for prolonged sedation in ICU due to active metabolites and accumulation. |
| Patient Advice | You may experience drowsiness, dizziness, or amnesia after receiving this medication. · Do not drive or operate heavy machinery for at least 24 hours after the procedure. · Avoid alcohol for at least 24 hours after receiving midazolam. · Grapefruit and grapefruit juice may increase the effects of midazolam; avoid consumption. · Inform your healthcare provider if you are pregnant, breastfeeding, or have a history of glaucoma or breathing problems. |