What medications can cause transaminitis?

Medications That Can Cause Transaminitis

Numerous medications can cause transaminitis (elevated liver transaminases), with some having higher risk profiles than others. The most common hepatotoxic medications include anti-tuberculosis drugs, statins, tyrosine kinase inhibitors, and certain antibiotics.

High-Risk Medications

Anti-tuberculosis Drugs

• Isoniazid: Causes transaminitis in approximately 10-20% of patients, with age-related risk (highest in those >50 years old at 2.3%) 1
• Rifampin: Can cause hepatotoxicity, especially when combined with isoniazid
• Pyrazinamide: High risk of hepatotoxicity, particularly in combination regimens
• Ethambutol: Lower risk compared to other TB medications but still associated with transaminitis 1

Tyrosine Kinase Inhibitors (TKIs)

• Lapatinib: Extensively metabolized with reactive metabolites that contribute to hepatotoxicity 1
• Pazopanib: Associated with transaminase elevations, especially when combined with statins 1
• Imatinib, Dasatinib, Erlotinib, Gefitinib, Nilotinib, Sorafenib, Sunitinib: All undergo bioactivation to form reactive intermediates that can cause idiosyncratic liver reactions 1

Statins

• Atorvastatin, Simvastatin, etc.: Cause transaminase elevations in approximately 1% of patients 2, 3
• Risk increases with higher doses and when combined with other hepatotoxic medications

Anticonvulsants

• Carbamazepine: Requires baseline and periodic liver function monitoring due to risk of hepatotoxicity 4
• Valproic acid: Can increase carbamazepine-10,11 epoxide plasma concentrations, potentially increasing toxicity 4

Moderate-Risk Medications

NSAIDs

• Diclofenac: Higher potential for hepatic problems compared to other NSAIDs
• Sulindac: Associated with higher risk of hepatotoxicity 1
• Most NSAIDs can cause primary hepatic complications that are usually reversible 1

Antimalarials/COVID-19 Treatments

• Chloroquine/Hydroxychloroquine: Rarely linked to aminotransferase elevations (LiverTox likelihood score D) 1, 2
• Remdesivir: Associated with elevated transaminases in 23% of patients in one case series 1
• Lopinavir/Ritonavir: Moderate-to-severe elevations in serum aminotransferases occur in 3-10% of patients 1

Immunomodulators

• Infliximab: Well-recognized to cause elevation in liver transaminases; rare cases of severe hepatitis and acute liver failure have been reported 1
• Methotrexate: Requires liver biopsy monitoring at high cumulative doses 2
• Acitretin: Elevation in transaminases seen in 13-16% of patients 1

Monitoring and Management

Monitoring Recommendations

• Baseline liver function tests before starting potentially hepatotoxic medications 2
• For mild elevations (<2× ULN): Continue medication and repeat testing in 2-4 weeks
• For moderate elevations (≥2× but <3× ULN): Consider dose reduction and close monitoring
• For significant elevations (≥3× but <5× ULN): Consider temporary discontinuation or dose reduction
• For severe elevations (>5× ULN): Discontinue medication and consider hepatology consultation 2

Risk Factors for Increased Hepatotoxicity

• Age >65 years
• Pre-existing liver disease
• Alcohol consumption
• Obesity
• Diabetes
• Concomitant use of multiple hepatotoxic medications 2

Special Considerations

• High daily dose: Medications with daily doses >50mg have been demonstrated to be a risk factor for adverse drug reactions, including hepatotoxicity 1
• Drug interactions: Concomitant use of drugs metabolized by the same enzymes can increase risk of hepatotoxicity (e.g., pazopanib and statins) 1
• Genetic factors: Some medications (e.g., isoniazid) may have increased risk in certain genetic populations

Remember that transaminitis can range from asymptomatic laboratory abnormalities to severe hepatotoxicity leading to liver failure. Early recognition and discontinuation of the offending agent is crucial for preventing progression to more severe liver injury.