What are examples of hepatotoxic medications?

From the Guidelines

Hepatotoxic medications include carbamazepine, methyldopa, minocycline, macrolide antibiotics, nitrofurantoin, statins, sulfonamides, terbinafine, chlorpromazine, and methotrexate, which can cause liver damage through various mechanisms, including direct damage to hepatocytes, formation of toxic metabolites, immune-mediated reactions, or mitochondrial dysfunction, as reported in a systematic review published in Gut in 2018 1.

Mechanisms of Hepatotoxicity

These medications can cause hepatotoxicity through different mechanisms, including:

• Direct damage to hepatocytes
• Formation of toxic metabolites
• Immune-mediated reactions
• Mitochondrial dysfunction

Examples of Hepatotoxic Medications

Some examples of hepatotoxic medications include:

• Antiepileptic drugs: carbamazepine
• Antibiotics: minocycline, macrolide antibiotics
• Antifungals: terbinafine
• Psychiatric medications: chlorpromazine
• Chemotherapy agents: methotrexate
• Statins: although rare, can cause liver injury, as demonstrated in studies published in Gut in 2018 1

Risk Factors for Hepatotoxicity

Patients with pre-existing liver disease, advanced age, alcohol use, or taking multiple hepatotoxic medications are at higher risk of developing hepatotoxicity, as noted in a study published in the American Journal of Respiratory and Critical Care Medicine in 2003 1.

Monitoring and Management

Regular liver function monitoring is essential when using these medications, and any signs of liver injury (jaundice, abdominal pain, fatigue) warrant immediate medical attention and possible medication discontinuation, as recommended in a guideline published in Thorax in 1998 1.

From the FDA Drug Label

BOXED WARNING HEPATOTOXICITY HEPATIC FAILURE RESULTING IN FATALITIES HAS OCCURRED IN PATIENTS RECEIVING VALPROIC ACID When Rifampin is given concomitantly with other hepatotoxic medications such as halothane or isoniazid, the potential for hepatotoxicity is increased.

Examples of hepatotoxic medications include:

• Valproic acid
• Halothane
• Isoniazid 2 3

From the Research

Hepatotoxic Medications

The following are examples of hepatotoxic medications:

• Antibiotics, such as isoniazid, rifampicin, and ethambutol 4, 5
• Antiretroviral drugs 6, 7
• Antituberculosis drugs, including isoniazid, rifampicin, and ethambutol 6, 4, 5
• Lipid-lowering agents, such as statins 6, 7
• Oral hypoglycemics, including thiazolidinediones (rosiglitazone, pioglitazone) 6, 7
• Psychotropics, such as nefazodone, pemoline, tacrine, carbamazepine, and valproate products (e.g., divalproex) 7, 8
• Acetaminophen 6, 7
• Complementary and alternative medications 7
• Methotrexate and niacin 6
• Tamoxifen 6

Mechanisms and Risks

These medications can cause various types of liver injury, including hepatitis, cholestasis, and chronic liver disease 4, 5. The risk of hepatotoxicity can be increased in patients with underlying liver disease 6, 4, 5. Clinical and biochemical monitoring is often recommended to minimize the risk of liver damage 6, 8.