Lorazepam (Ativan) Does Not Require Dose Adjustment in Chronic Kidney Failure
Lorazepam can be safely used at standard doses in patients with chronic kidney disease and end-stage renal disease without dose adjustment, as it is metabolized by the liver to an inactive glucuronide conjugate and does not accumulate in renal failure. 1, 2
Why Lorazepam is Safe in Renal Failure
The parent drug lorazepam undergoes hepatic glucuronidation to an inactive, nontoxic metabolite that does not cause clinical problems even when it accumulates. 1 This distinguishes lorazepam from other benzodiazepines:
- Lorazepam clearance remains unchanged in renal impairment (approximately 85 ml/min in patients vs 71 ml/min in normals, not statistically different) 1
- The plasma half-life of lorazepam in chronic renal failure patients (11.3 hours) is identical to normal subjects (11.1 hours) 2
- Only 2% of lorazepam is excreted unchanged in urine; the remaining 98% undergoes hepatic metabolism 1
- The glucuronide metabolite that accumulates is pharmacologically inactive and nontoxic 1
Contrast with Other Benzodiazepines
Diazepam should be avoided in renal failure because it produces active metabolites that accumulate and cause prolonged sedation. 3, 4 This is a critical distinction:
- Diazepam has active metabolites that can accumulate in renal insufficiency 3
- The elimination half-life and duration of clinical effect of lorazepam are increased in renal failure, but this is due to the inactive glucuronide, not the active drug 3
Practical Dosing Recommendations
Standard lorazepam doses can be used in chronic kidney disease without adjustment. 3, 1 Specific guidance:
- For anxiolysis in dental procedures: 0.5-1 mg lorazepam can be used without dose adjustment 3
- For sedation in ICU: Standard doses apply, though elderly patients require lower doses due to age-related sensitivity, not renal impairment 3
- For crisis management of severe agitation: 0.25-0.5 mg subcutaneous or intravenous every 1 hour as needed in frail patients 3
Important Caveats
While dose adjustment is not required for renal impairment, use lower doses in elderly or frail patients regardless of renal function. 3 Consider:
- Elderly patients are significantly more sensitive to benzodiazepine sedative effects independent of renal function 3
- Combining lorazepam with opioids increases risk of respiratory depression 3
- High-dose olanzapine combined with benzodiazepines has caused fatalities due to oversedation and respiratory depression 3
- Lorazepam can cause respiratory depression and hypotension, especially in patients with baseline cardiopulmonary instability 3
Hemodialysis Considerations
Hemodialysis removes minimal lorazepam (only 8% over 6 hours) but removes 40% of the glucuronide metabolite. 1 This means: