What is the recommended dosing for Ativan (lorazepam) in elderly patients with impaired renal or hepatic function?

Ativan (Lorazepam) Dosing in the Elderly

In elderly patients, start lorazepam at 0.5-1 mg daily (maximum 2 mg in 24 hours), which is half the standard adult dose, and adjust carefully based on response; no dose adjustment is required for renal or hepatic impairment since lorazepam undergoes glucuronidation rather than oxidative metabolism. 1

Initial Dosing Strategy

• Start with 0.5-1 mg orally for anxiety or agitation, with a maximum of 2 mg in 24 hours for elderly or debilitated patients 2
• The FDA label explicitly states that elderly patients should not exceed an initial dose of 2 mg and requires careful monitoring with frequent dosage adjustments 1
• For severe anxiety requiring more frequent dosing, use 0.25-0.5 mg four times daily (maximum 2 mg in 24 hours) in elderly patients, compared to 0.5-1 mg four times daily (maximum 4 mg in 24 hours) in younger adults 2

Advantages in Renal and Hepatic Impairment

Lorazepam is the preferred benzodiazepine in elderly patients with organ dysfunction because it undergoes only glucuronidation, not oxidative metabolism. 3

• Unlike chlordiazepoxide or diazepam, lorazepam metabolism is minimally affected by age and liver disease since it bypasses hepatic oxidation 3
• Renal impairment does not significantly alter lorazepam clearance (approximately 85 ml/min in renal patients vs 71 ml/min in normals), so no dosage adjustment is necessary for renal disease 4
• The elimination half-life is 8-25 hours with clearance of 0.7-1.2 ml/min/kg, and while clearance is somewhat reduced in old age, this is accounted for by using lower starting doses 5
• Lorazepam is extensively metabolized to an inactive, nontoxic glucuronide conjugate that is renally eliminated, with only 2% excreted unchanged 4

Hepatic Considerations

• While lorazepam is safer than oxidatively metabolized benzodiazepines, use with caution in severe hepatic insufficiency and monitor hepatic function regularly 1
• The FDA warns that benzodiazepines may worsen hepatic encephalopathy, so lower doses may be sufficient and careful titration is essential 1
• Patients with liver disease should still be monitored, but lorazepam remains the empirically safest choice among benzodiazepines for this population 3

Route of Administration

• Oral tablets can be used sublingually for faster onset when patients have difficulty swallowing 2
• Lorazepam has predictable intramuscular absorption (>90% bioavailability) unlike chlordiazepoxide or diazepam, making it suitable for parenteral use when needed 3, 5
• For patients unable to swallow, consider switching to subcutaneous midazolam 2.5-5 mg every 2-4 hours (reduced to 5 mg over 24 hours if eGFR <30 mL/min) 2

Critical Safety Monitoring

• Monitor frequently for excessive sedation, respiratory depression, and paradoxical reactions (agitation, confusion), which are more common in elderly patients 1
• Assess for compromised respiratory function (COPD, sleep apnea) before prescribing, as lorazepam should be used with extreme caution in these patients 1
• Never combine with opioids unless absolutely necessary and under close supervision due to risk of fatal respiratory depression 1
• Watch for signs of abuse, misuse, and physical dependence; abrupt discontinuation can precipitate life-threatening withdrawal reactions 1

Common Pitfalls to Avoid

• Do not use standard adult doses (2-6 mg daily) in elderly patients—this is the most common prescribing error 1
• Avoid prolonged use without monitoring for upper GI symptoms, as animal studies showed esophageal dilation with chronic use 1
• Do not assume dose adjustments are needed for renal impairment as with other medications—lorazepam clearance remains stable 4
• Recognize that lorazepam's relatively short half-life (compared to diazepam) makes it preferable for elderly patients to minimize accumulation 6