What is the onset time of lorazepam (Ativan) after oral, intramuscular, and intravenous administration, and how do older age or hepatic impairment affect it?

Lorazepam Onset Time by Route of Administration

Lorazepam's onset varies dramatically by route: IV begins working in 1-2 minutes, IM in 15-20 minutes, and oral in 20-30 minutes, with elderly patients and those with hepatic impairment experiencing similar onset times but prolonged duration of effect. 1, 2

Route-Specific Onset and Peak Times

Intravenous Administration

• Initial clinical effects begin within 1-2 minutes, though this represents the very beginning of drug action rather than peak sedation 1, 3
• Peak effects are not immediate despite rapid onset 3
• Administer over approximately 2 minutes (not rapid IV push) to avoid pain at the IV site 3

Intramuscular Administration

• Onset occurs at 15-20 minutes after injection 4, 1, 2
• Peak effects at approximately 60-90 minutes post-injection 1, 2
• Duration of effect is 6-8 hours 4, 2
• Absorption is rapid and nearly complete (80-100% bioavailability) 5, 6

Oral Administration

• Onset time is 20-30 minutes after ingestion 4, 1, 2
• Peak effects at approximately 2 hours after administration 1, 2, 7
• Effective concentrations are obtained within 30-60 minutes and maintained for 4-6 hours 7
• Absorption is rapid and nearly complete (approximately 100% bioavailability) 6

Impact of Age and Hepatic Impairment

Elderly Patients

• Onset time itself is NOT significantly prolonged in elderly patients 5
• However, elderly patients have 22% reduced total clearance (0.77 ml/min/kg vs 0.99 ml/min/kg in young subjects), which prolongs duration rather than onset 5
• Elimination half-life in elderly (15.9 hours) does not differ significantly from young subjects (14.1 hours) 5
• Elderly patients are significantly more sensitive to sedative effects, requiring dose reductions of 20% or more 4, 1
• Smaller volume of distribution (0.99 L/kg vs 1.11 L/kg in young) suggests less extensive drug distribution 5

Hepatic Impairment

• Benzodiazepine clearance is reduced in hepatic dysfunction, affecting duration but not necessarily onset time 1
• Dose reduction is required in patients with hepatic impairment 4
• Midazolam clearance (a related benzodiazepine) is specifically noted to be reduced in hepatic impairment, and similar considerations apply to lorazepam 4

Critical Safety Monitoring During Onset Period

Respiratory Depression

• Respiratory depression is the major adverse effect and may occur even at therapeutic doses, particularly when combined with opioids 1, 2, 3
• The synergistic effect with opioids requires dose reduction and heightened vigilance 1, 3
• Continuous monitoring for respiratory depression is essential during the onset period and throughout duration of effect 2, 3
• Respiratory support must be immediately available when administering IV lorazepam 3

Cardiovascular Effects

• Hypotension may occur, especially in hemodynamically unstable patients or when combined with other CNS depressants 1
• Elderly patients and those with baseline cardiovascular instability are at higher risk 1

Paradoxical Reactions

• Approximately 10% of patients may experience paradoxical reactions (agitation rather than sedation) 3
• Younger patients and those with developmental disabilities are particularly susceptible to behavioral disinhibition 2, 3

Extended Monitoring Requirements

Extended monitoring is essential even after apparent recovery due to the elimination half-life of approximately 12 hours 1, 2, 3. Sufficient drug remains after 24 hours to suggest that residual CNS effects may still be present 7.