Lorazepam

Benzodiazepine, Anxiolytic, Schedule IV controlled substance

Lorazepam

Ativan (oral, injectable), Loreev XR

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Summary

Classes

Benzodiazepine, Anxiolytic, Schedule IV controlled substance

Pharmacy

Starting dose

Anxiety: 0.5-1 mg PO BID-TID. Insomnia: 1-2 mg PO at bedtime. Status epilepticus: 4 mg IV (adult), repeat after 5-10 minutes if needed. Acute agitation: 1-2 mg IM

Preparations

Tablets 0.5, 1, 2 mg; oral concentrate 2 mg/mL; injection 2 mg/mL and 4 mg/mL; Loreev XR capsules 1, 2, 3 mg

US FDA Max

10 mg/day (anxiety, oral)

Pharmacology

Routes

Oral, intramuscular, intravenous

Onset

30-60 minutes (oral); 5 minutes (IV); 15-30 minutes (IM)

Duration

6-8 hours

Half-life

12-15 hours (intermediate); no active metabolites (key clinical feature)

Bioavailability

~90% (oral)

Pregnancy

Some signal for cleft lip/palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.^{[citation needed]}

Legal status

Schedule IV controlled substance in US. Carries the benzodiazepine class Boxed Warning for risk of fatal respiratory depression, coma, and death when combined with opioids

Purported mechanism

Positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site (α-γ subunit interface), enhancing chloride ion conductance and consequent neuronal inhibition. The intermediate half-life sits between short-acting alprazolam and long-acting diazepam/clonazepam, making lorazepam a clinically versatile choice.▲0▼ Metabolized by glucuronidation rather than CYP, so unlike alprazolam and diazepam, lorazepam has minimal CYP-mediated interactions, and the lack of active metabolites makes it the preferred benzodiazepine in elderly patients and in hepatic impairment. Tolerance, dependence, and significant withdrawal syndrome on abrupt discontinuation; slow taper essential after extended use.