What medications can affect the liver or increase liver enzymes?

From the Guidelines

Medications that can affect the liver or increase liver enzymes include antiretroviral agents, statins, certain antibiotics, antiepileptic drugs, and antifungals, among others, as reported in studies such as 1 and 1.

Medications Affecting the Liver

These medications can cause liver damage or increase liver enzymes through various mechanisms, including direct toxicity, immune-mediated reactions, or interference with bile flow.

• Antiretroviral agents, such as nevirapine, can cause severe clinical hepatotoxicity, especially in patients coinfected with hepatitis C virus, as noted in 1.
• Statins, like atorvastatin and simvastatin, can elevate hepatic transaminases in a dose-dependent manner, although progression to liver failure is rare, as stated in 1.
• Certain antibiotics, including amoxicillin-clavulanate, isoniazid, and fluoroquinolones, can also impact liver function.
• Antiepileptic drugs, such as valproic acid, phenytoin, and carbamazepine, and antifungals like ketoconazole and fluconazole, are additional examples of medications that can affect the liver.

Mechanisms and Risks

The liver processes most medications, and during metabolism, reactive compounds may form that can damage liver tissue.

• Liver enzyme elevations may be mild and transient or indicate more serious liver injury.
• Regular liver function monitoring may be necessary, especially during the initial treatment period, for patients taking these medications.
• It is essential to take medications as prescribed, avoid alcohol when taking potentially hepatotoxic drugs, and inform healthcare providers about all medications being taken to minimize liver-related risks.

Key Considerations

Given the potential for liver damage or enzyme elevation, it is crucial to:

• Be aware of the medications that can affect the liver
• Monitor liver function regularly when taking these medications
• Avoid alcohol and other hepatotoxic substances
• Inform healthcare providers about all medications being taken to ensure safe and effective treatment.

From the FDA Drug Label

Hepatic Dysfunction Inform patients that atorvastatin calcium tablets may cause liver enzyme elevations and possibly liver failure. Other associated manifestations may include lymphadenopathy, hepatitis, liver function test abnormalities, hematological abnormalities (e.g., eosinophilia, thrombocytopenia, neutropenia), pruritis, nephritis, oliguria, hepato-renal syndrome, arthralgia, and asthenia.

Medications that can affect the liver or increase liver enzymes:

• Atorvastatin calcium tablets may cause liver enzyme elevations and possibly liver failure 2
• Valproate has been associated with hepatitis, liver function test abnormalities 3 Key points:
• Patients should be advised to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice if they are taking atorvastatin calcium tablets 2
• Valproate should be discontinued if a hepatic reaction is suspected 3

From the Research

Medications that Affect the Liver or Increase Liver Enzymes

• Paracetamol (also known as acetaminophen) is a widely used anti-pyretic that can cause liver toxicity once above therapeutic levels 4.
• Antiepileptic drugs (AEDs) such as phenobarbital, phenytoin, and carbamazepine can stimulate the synthesis of a broad range of monooxygenase and conjugating enzymes, which can lead to increased liver enzyme levels 5.
• Other AEDs such as oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate, and perampanel have weaker inducing properties, but can still cause interactions mediated by enzyme induction 6.
• Enzyme-inducing AEDs can also affect enzymes involved in endogenous metabolic pathways, leading to alterations in bone biochemistry, gonadal steroids, and lipid markers 5.
• Interactions between AEDs and other drugs can also occur, resulting in changes in absorption, distribution, or elimination, and can lead to increased liver enzyme levels or liver damage 6.

Specific Medications that Increase Liver Enzymes

• Paracetamol can increase liver enzymes, especially when taken above therapeutic levels or in combination with other medications 4.
• Phenobarbital, phenytoin, and carbamazepine can increase liver enzymes due to their enzyme-inducing properties 5.
• Other medications such as oral anticoagulants, calcium antagonists, steroids, antimicrobial and antineoplastic drugs can also be affected by enzyme-inducing AEDs, leading to increased liver enzyme levels 5, 6.