Lorazepam
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Lorazepam
Ativan (oral, injectable), Loreev XR
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Summary
Common uses
Anxiety disorders (FDA)0, Preoperative sedation (FDA, IV)0, Status epilepticus (FDA, IV; first-line per current guidelines)0, Alcohol withdrawal (off-label, often first-line in hepatic impairment)0, Acute agitation (off-label, IM)0, Chemotherapy-induced nausea (off-label adjunct)0
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)[1]
Bioavailability
~90% (oral)[1]
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[1]
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[1].
References
- ↑ 1.0 1.1 1.2 1.3 FDA Prescribing Information, Ativan (lorazepam), Bausch/Pfizer, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017794s044lbl.pdf