What medications are contraindicated in patients with hepatitis and elevated liver enzymes (transaminases)?

From the Guidelines

Patients with hepatitis and elevated liver enzymes should avoid medications such as carbamazepine, methyldopa, minocycline, macrolide antibiotics, nitrofurantoin, sulfonamides, terbinafine, chlorpromazine, and methotrexate, as they are associated with liver disease and may worsen liver damage. According to the guidelines on the management of abnormal liver blood tests 1, these drugs can cause liver injury and should be used with caution or avoided in patients with pre-existing liver disease. Additionally, medications like statins, which can lead to drug-induced liver injury, although rare, should be monitored closely 1.

In general, medications that undergo hepatic metabolism and can cause direct hepatotoxicity should be avoided or used with caution in patients with hepatitis and elevated liver enzymes. This includes medications like isoniazid, which can cause hepatitis and should be used with caution in patients with pre-existing liver disease 1. Alternative medications with less hepatic metabolism should be considered when possible, and liver function tests should be regularly monitored when any medication is necessary.

Some key points to consider when prescribing medications to patients with hepatitis and elevated liver enzymes include:

• Avoiding medications that are known to cause liver injury or worsen liver disease
• Monitoring liver function tests regularly when medications are necessary
• Considering alternative medications with less hepatic metabolism
• Using caution when prescribing medications that undergo hepatic metabolism and can cause direct hepatotoxicity
• Avoiding alcohol and medications that can exacerbate liver damage, such as acetaminophen at high doses and certain antifungals like ketoconazole.

It is essential to exercise clinical judgment when determining the relative contribution of a drug or drugs to liver blood abnormalities and to consider the pattern of liver blood tests, the timing of medication use, and the clinical setting 1. By taking a cautious approach and carefully considering the potential risks and benefits of medications, healthcare providers can help minimize the risk of worsening liver damage in patients with hepatitis and elevated liver enzymes.

From the Research

Contraindicated Drugs in Hepatitis with Elevated Liver Enzymes

• The following drugs are contraindicated in hepatitis with elevated liver enzymes:
  • Acetaminophen 2
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) 2
  • Statins are contraindicated in advanced end-stage liver disease, but can be used in patients with chronic, stable hepatitis C with elevated cardiac risk or a previous cardiac event 3
• Other drugs that may cause liver enzyme elevations include:
  • Checkpoint inhibitor immunotherapy 4
  • Certain medications that can cause drug-induced liver disease 5

Patterns of Liver Enzyme Elevations

• There are three different patterns of increased liver enzymes:
  • Predominant increase in transaminase activities, which reflects a disturbance of hepatocellular integrity 5
  • High serum alkaline phosphatase and γ-glutamyltranspeptidase activities, indicating cholestatic liver diseases 5
  • Predominant rise in γ-glutamyl transpeptidase, which is observed in alcoholic or non-alcoholic fatty liver disease and infiltrating liver diseases 5

Evaluation and Management of Elevated Liver Enzymes

• Evaluation should be guided by both the clinical presentation and the pattern of injury 6
• A biochemical signature with higher ALT and ALT/AST ratio, a history of prior ICI exposure, and other organ immunotoxicities may help to identify patients at a higher likelihood of immunotoxicity 4
• Liver biopsy can be safely deferred in most patients with liver enzyme elevations following ICI exposure 4