Is oral terbinafine (antifungal medication) hepatotoxic (toxic to the liver)?

Hepatotoxicity of Oral Terbinafine

Yes, oral terbinafine can cause liver toxicity, with cases of liver failure reported that have led to liver transplant or death in some individuals, particularly those with pre-existing liver disease. 1

Risk of Hepatotoxicity

Terbinafine has been associated with serious hepatotoxicity, though it is relatively rare:

• The FDA label explicitly warns about cases of liver failure, some leading to liver transplant or death 1
• Hepatotoxicity can occur in patients with and without pre-existing liver disease, though the severity may be worse in those with active or chronic liver disease 1
• The British Journal of Dermatology recommends baseline liver function tests for high-risk patients, including those with history of heavy alcohol consumption, hepatitis, or pre-existing liver disease 2
• The estimated risk of symptomatic idiosyncratic hepatobiliary dysfunction is approximately 1:45,000-1:54,000 patients 3

Pattern of Liver Injury

When terbinafine causes liver injury, it typically presents as:

• Mixed hepatocellular and cholestatic injury 3
• Onset typically occurs 4-6 weeks after starting treatment 3
• Symptoms may include persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools 1

Monitoring Recommendations

Due to the risk of hepatotoxicity, the following monitoring is recommended:

• Liver function tests should be performed before prescribing terbinafine 1
• Periodic monitoring of liver function is recommended during treatment 1
• The US terbinafine product monograph suggests assessing hepatic enzymes in individuals receiving terbinafine for more than 6 weeks 3
• Some physicians monitor liver values at baseline and at 4-6 weeks 3

Contraindications and Precautions

Terbinafine is not recommended for:

• Patients with chronic or active liver disease 1
• Patients with a history of allergic reaction to oral terbinafine 1

Clinical Considerations

When considering terbinafine therapy:

• Treatment should be immediately discontinued if biochemical or clinical evidence of liver injury develops 1
• Patients should be warned to report immediately any symptoms suggestive of liver injury 1
• For patients who absolutely require terbinafine despite liver concerns, consider:
  • Consulting with a hepatologist 4
  • Limiting exposure to less than 6 weeks when possible 4
  • Close monitoring of liver function tests 4
  • Patient education about signs and symptoms of liver injury 4

Other Significant Adverse Effects

Besides hepatotoxicity, terbinafine can cause:

• Taste disturbance, including taste loss (can be severe and potentially permanent) 1
• Smell disturbance, including loss of smell (may be prolonged or permanent) 1
• Depressive symptoms 1
• Hematologic effects, including transient decreases in absolute lymphocyte counts 1
• Serious skin reactions (e.g., Stevens-Johnson Syndrome and toxic epidermal necrolysis) 1

While terbinafine is an effective antifungal medication, its potential for hepatotoxicity requires careful consideration of risks versus benefits, particularly in patients with any history of liver disease.