Oxazepam and Lorazepam Are Intermediate-Acting Benzodiazepines
Both oxazepam and lorazepam are classified as intermediate-acting benzodiazepines with half-lives between 10-24 hours, not short-acting benzodiazepines. 1
Pharmacokinetic Properties
Lorazepam
- Elimination half-life: 8 to 25 hours 2
- Volume of distribution: 1.0 to 1.3 L/kg
- Clearance: 0.7 to 1.2 ml/min/kg
- High systemic availability (≥90%) when administered orally or intramuscularly
- Free fraction in plasma: 8-12%
Oxazepam
- Elimination half-life: 5 to 15 hours 2
- Volume of distribution: 0.6 to 2.0 L/kg
- Clearance: 0.9 to 2.0 ml/min/kg
- Free fraction in plasma: 2-4%
Clinical Significance in Special Populations
Hepatic Dysfunction
- Both lorazepam and oxazepam are preferred in patients with hepatic dysfunction 3
- Unlike long-acting benzodiazepines, they have minimal accumulation of active metabolites and more predictable metabolism 1
- Lorazepam is specifically recommended for patients with liver failure at dosages of 1-4 mg every 4-8 hours 1
- For patients with severe hepatic insufficiency, lower initial doses (0.25-0.5 mg) are recommended 1
Elderly Patients
- Both are safer in elderly patients compared to long-acting benzodiazepines 3
- However, elderly patients still have heightened sensitivity to all benzodiazepine side effects 1
- Lorazepam clearance is somewhat reduced in old age 2
- In psychogeriatric patients, both drugs have shown efficacy as sleeping aids, though with some muscle relaxant side effects after awakening 4
Accumulation and Chronic Use
- In theory, accumulation does not occur with once-daily dosing of benzodiazepines that have elimination half-lives markedly shorter than 24 hours, such as oxazepam and lorazepam 5
- This is an advantage over long-acting benzodiazepines like diazepam, which has a half-life >24 hours and tends to accumulate with repeated dosing 1
Clinical Applications
- For alcohol withdrawal syndrome, short and intermediate-acting benzodiazepines (including lorazepam and oxazepam) are safer in elderly patients and those with hepatic dysfunction 3
- For episodic anxiety, shorter-acting drugs like oxazepam or lorazepam are usually preferred, while sustained levels of anxiety normally respond better to longer-acting benzodiazepines 6
Important Considerations and Cautions
- Despite their intermediate half-life, both drugs can still cause dependence with prolonged use 1
- Duration of use should ideally be limited to 4 weeks maximum to prevent tolerance and dependence
- Concomitant use with opioids increases the risk of severe respiratory depression and death 1
- Patients should avoid alcohol consumption and driving or operating machinery while taking these medications 1
Bottom Line
While oxazepam and lorazepam are sometimes referred to as "shorter-acting" in comparison to very long-acting benzodiazepines like diazepam, they are properly classified as intermediate-acting benzodiazepines based on their half-lives of 10-24 hours. This intermediate action profile makes them particularly useful in patients with hepatic dysfunction or elderly patients where long-acting benzodiazepines would pose greater risks.