Therapeutic Classification: antianxiety agents, anticonvulsants, sedative/hypnotics
Pharmacologic Classification: benzodiazepines
Absorption: Rapidly absorbed following oral and nasal administration; undergoes substantial intestinal and first-pass hepatic metabolism. Well absorbed following IM administration; IV administration results in complete bioavailability.
Distribution: Crosses the blood-brain barrier and placenta; excreted in breast milk.
Protein Binding: 97%.
Metabolism/Excretion: Almost exclusively metabolized by the liver by the CYP3A4 isoenzyme, resulting in conversion to hydroxymidazolam, an active metabolite, and 2 other inactive metabolites; metabolites are excreted in urine.
Half-Life: Preterm neonates: 2.6–17.7 hr; Neonates: 4–12 hr; Children: 3–7 hr; Adults: 2–6 hr (↑ in renal impairment, HF, or cirrhosis).
Preoperative Sedation/Anxiolysis/Amnesia
- PO (Children 6 mo–16 yr): 0.25–0.5 mg/kg; may require up to 1 mg/kg (dose should not exceed 20 mg); Patients with cardiac/respiratory compromise or concurrent CNS depressants: 0.25 mg/kg.
- IM (Adults <60 yr, otherwise healthy ): 0.07–0.08 mg/kg 1 hr before surgery (usual dose 5 mg).
- IM (Adults ≥60 yr, debilitated or chronically ill): 0.02–0.03 mg/kg 1 hr before surgery (usual dose 1–3 mg).
- IM (Children ): 0.1–0.15 mg/kg up to 0.5 mg/kg 30–60 min prior to procedure; not to exceed 10 mg/dose.
Conscious Sedation for Short Procedures
- IV (Adults and Children >12 yr and <60 yr, otherwise healthy): 1–2.5 mg initially; dosage may be ↑ further as needed. Total doses >5 mg are rarely needed (↓ dose by 50% if other CNS depressants are used). Maintenance doses of 25% of the dose required for initial sedation may be given as necessary.
- IV (Children 6–12 yr): 0.025–0.05 mg/kg initially; then titrate dose carefully; may need up to 0.4 mg/kg total; maximum dose 10 mg.
- IV (Children 6 mo–5 yr): 0.05 mg/kg initially; then titrate dose carefully; may need up to 0.6 mg/kg total; maximum dose 6 mg.
- IV Geriatric Patients ≥60 yr, debilitated or chronically ill): 1–1.5 mg initially; dose may be ↑ further as needed. Total doses >3.5 mg are rarely needed (↓ dose by 30% if other CNS depressants are used). Maintenance doses of 25% of the dose required for initial sedation may be given as necessary.
- (Children ): 0.2–0.3 mg/kg, may repeat in 5–15 min.
Status Epilepticus
- IM (Adults ): 10 mg single dose.
- IV (Children >2 mo): 0.15 mg/kg load followed by a continuous infusion of 1 mcg/kg/min. Titrate dose upward every 5 min until seizure controlled, range: 1–18 mcg/kg/min.
Seizure Clusters
- (Adults and Children ≥12 yr): One spray (5 mg) into one nostril initially; if inadequate response after 10 min, administer one spray (5 mg) into other nostril. Not to exceed 2 doses for a single seizure episode. Should not be used to treat more than one episode every 3 days and no more than 5 episodes per mo.
Induction of Anesthesia (Adjunct)
- IV (Adults <55 yr, otherwise healthy): 300–350 mcg/kg initially (up to 600 mcg/kg total). May give additional dose of 25% of initial dose if needed. If patient is premedicated, initial dose should be further ↓.
- IV Geriatric Patients >55 yr): 150–300 mcg/kg as initial dose. May give additional dose of 25% of initial dose if needed. If patient is premedicated, initial dose should be further ↓.
- IV (Adults , debilitated): 150–250 mcg/kg initial dose. May give additional dose of 25% of initial dose if needed. If patient is premedicated, initial dose should be further ↓.
Sedation in Critical Care Settings
- IV (Adults ): 0.01–0.05 mg/kg (0.5–4 mg in most adults) initially if a loading dose is required; may repeat every 10–15 min until desired effect is obtained; may be followed by infusion at 0.02–0.1 mg/kg/hr (1–7 mg/hr in most adults).
- IV (Children ): Intubated patients only: 0.05–0.2 mg/kg initially as a loading dose; follow with infusion at 0.06–0.12 mg/kg/hr (1–2 mcg/kg/min); titrate to effect, range: 0.4–6 mcg/kg/min.
- IV (Neonates >32 wk): Intubated patients only: 0.06 mg/kg/hr (1 mcg/kg/min).
- IV (Neonates <32 wk): Intubated patients only: 0.03 mg/kg/hr (0.5 mcg/kg/min).
