Half-Life of Ativan (Lorazepam)
The elimination half-life of lorazepam is approximately 12 hours in adults, with a range of 8-25 hours depending on individual patient factors. 1
Standard Adult Half-Life
- The mean half-life of unconjugated lorazepam in human plasma is about 12 hours, as stated in the FDA drug label 1
- Research studies consistently confirm this 12-hour half-life across multiple investigations 2, 3
- The major metabolite, lorazepam glucuronide (which is inactive), has a slightly longer half-life of approximately 18 hours 1
Half-Life Variations by Route of Administration
- Oral lorazepam: elimination half-life averages 12 hours (range 9.68-18.42 hours) 3, 4
- Intravenous lorazepam: terminal half-life of 14.10 hours (±2.94 SD) 4
- Intramuscular lorazepam: half-life of 13.6 hours, with rapid absorption reaching peak concentrations within 3 hours 5
The route of administration does not significantly alter the elimination half-life, though absorption kinetics differ 4, 5.
Pediatric Population Half-Life
- Infants: elimination half-life is markedly prolonged at approximately 40 hours 6
- Children: elimination half-life is approximately 10.5 hours 6
This age-dependent variation is clinically significant when converting from midazolam to lorazepam in pediatric patients, as lorazepam has a sixfold longer half-life than midazolam 7.
Special Population Considerations
Elderly Patients
- Advancing age does not significantly affect lorazepam pharmacokinetics in most studies 1
- However, one study showed mean total body clearance decreased by 20% in elderly subjects (60-84 years) compared to younger subjects (19-38 years) 1
- Complete clearance time may be extended in elderly patients 6
Renal Impairment
- The elimination half-life may be increased in patients with renal failure 6
- Renal disease is associated with prolonged half-life and increased volume of distribution 8
Hepatic Impairment
- Benzodiazepine clearance is reduced in patients with hepatic dysfunction 6
- However, liver disease has minimal effect on lorazepam clearance compared to other benzodiazepines, since lorazepam undergoes direct glucuronidation rather than oxidative metabolism 8
Clinical Implications
- Steady-state blood levels occur within 2-3 days of multiple dosing and are directly proportional to the daily dose 2
- The active drug and glucuronide conjugate are completely eliminated from the blood within 1 week following the last dose 2
- For procedural sedation, patients require monitoring for up to 2 hours post-administration of IV lorazepam 9
- When weaning from continuous IV benzodiazepines, the required time is proportional to the duration of treatment, and lorazepam's longer half-life must be factored into clinical decision-making 7, 6