Is Ativan (Lorazepam) Safe in Elevated AST and ALT?
Lorazepam is actually one of the safest benzodiazepines for patients with elevated liver enzymes and is specifically preferred over other benzodiazepines in liver disease because it undergoes only glucuronidation, which is minimally affected by hepatic impairment. 1
Why Lorazepam is Preferred in Liver Dysfunction
Lorazepam metabolism is minimally affected by liver disease because it undergoes only hepatic glucuronidation, unlike chlordiazepoxide and diazepam which require hepatic oxidation first—a process that is significantly impaired in liver disease 1
Lorazepam appears to be the safest empiric choice among benzodiazepines for patients with liver disease, as oxidative metabolism (required by other benzodiazepines) is decreased in persons with liver disease, leading to accumulation with resultant excessive sedation and respiratory depression 1
In a direct comparison study, lorazepam showed similar efficacy to chlordiazepoxide with no clinically significant withdrawal complications, and the authors specifically noted that lorazepam "could be used with confidence when liver disease or the inability to determine liver function status renders chlordiazepoxide therapy problematic" 2
Important FDA Warnings and Precautions
Despite its relative safety, the FDA label includes specific cautions:
"Lorazepam should be used with caution in patients with severe hepatic insufficiency and/or encephalopathy" because all benzodiazepines may worsen hepatic encephalopathy 3
Dosage should be adjusted carefully according to patient response; lower doses may be sufficient in patients with severe hepatic insufficiency 3
Periodic liver-function tests are recommended for patients on long-term therapy, as some patients on lorazepam have developed elevations of LDH 3
Clinical Decision Algorithm
For mild to moderate liver enzyme elevations (ALT/AST <5× ULN):
- Lorazepam can be prescribed at standard dosing without specific monitoring requirements 4
- Monitor liver enzymes as part of the workup for the underlying cause of elevation 4
For severe liver enzyme elevations (ALT/AST ≥5× ULN):
- Exercise caution with all medications, including lorazepam 4
- Consider starting at lower doses and titrating based on response 3
- Monitor liver function within 1-2 weeks of starting lorazepam 4
- If AST/ALT levels increase significantly after starting lorazepam (>2× baseline), consider discontinuation 4
For patients with hepatic encephalopathy:
- Use with extreme caution as lorazepam may worsen encephalopathy 3
- Consider alternative non-benzodiazepine options if possible
Critical Caveats
Rare hepatotoxicity has been reported: One case report documented drug-induced liver injury from lorazepam after 5 months of use, which resolved 59 days after cessation 5. This serves as a reminder that even "safe" drugs can rarely cause liver injury.
The elevation pattern matters: If your patient has elevated ALT/AST, first determine the underlying cause (NAFLD, viral hepatitis, alcohol, medications) before attributing any changes to lorazepam 6, 7
Drug interactions are critical: Lorazepam produces increased CNS-depressant effects when combined with alcohol, opioids, or other CNS depressants, which is particularly dangerous in patients with compromised liver function 3
Avoid in advanced cirrhosis with synthetic dysfunction: If the patient has evidence of hepatic decompensation (elevated bilirubin >2× ULN, low albumin, prolonged PT/INR), extreme caution is warranted as tissue responsiveness to psychoactive agents is increased 8