Terbinafine Discontinuation Thresholds for Elevated Liver Enzymes
Discontinue terbinafine immediately if ALT or AST ≥3× ULN with total bilirubin ≥2× ULN or INR >1.5, or if ALT/AST ≥3× ULN with hepatic symptoms (jaundice, right upper quadrant pain, nausea, vomiting, fatigue), or if ALT/AST ≥8× ULN alone. 1
Algorithmic Approach to Discontinuation
For Patients with Normal Baseline Liver Function
The FDA label and regulatory guidelines provide clear stopping rules 2, 1:
Discontinue terbinafine if ANY of the following occur:
- ALT or AST ≥8× ULN (regardless of symptoms) 2
- ALT or AST ≥5× ULN persisting for more than 2 weeks 2
- ALT or AST ≥3× ULN with total bilirubin ≥2× ULN or INR >1.5 (Hy's Law criteria - indicates severe hepatocellular injury with high mortality risk) 2, 1
- ALT or AST ≥3× ULN with hepatic symptoms including fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, jaundice, dark urine, or pale stools 2, 1
For Patients with Pre-existing Elevated Liver Enzymes (Baseline ALT >1.5× ULN)
Discontinue terbinafine if ANY of the following occur:
- ALT ≥5× baseline OR ≥500 U/L (whichever occurs first) 2
- ALT ≥2× baseline OR ≥300 U/L (whichever occurs first) AND total bilirubin ≥2× ULN 2
- ALT ≥2× baseline OR ≥300 U/L (whichever occurs first) AND hepatic symptoms (severe fatigue, fever, right upper quadrant pain, nausea, vomiting) 2
Critical Clinical Context
Why Immediate Discontinuation Matters
Delayed discontinuation can result in irreversible liver failure and death. 2 The FDA label explicitly warns that cases of liver failure leading to liver transplant or death have occurred with terbinafine use 1. The severity of hepatic events may be worse in patients with active or chronic liver disease 1.
Symptom Recognition is Key
Most patients with terbinafine-induced severe liver injury are symptomatic, typically presenting with jaundice, abdominal pain, general malaise, and severe pruritus 3. The mean duration from starting terbinafine to symptom onset is approximately 30 days (range 5-84 days), with most cases occurring between 4-6 weeks 3. No asymptomatic patients were identified through laboratory screening alone in published case series 3.
Important Caveats and Pitfalls
Pre-existing Liver Disease
Terbinafine is not recommended for patients with chronic or active liver disease. 1 The FDA label states that terbinafine should not be used in patients with chronic or active liver disease, and the British Association of Dermatologists advises avoiding use in these patients 4. However, if absolutely necessary after hepatologist consultation, a short course (<6 weeks) with intensive monitoring may be considered 5.
Renal Impairment Considerations
Terbinafine is contraindicated in patients with creatinine clearance ≤50 mL/min, as it is primarily cleared by the kidneys 4. This is an absolute contraindication, not a dose-adjustment scenario 4.
The "Hy's Law" Combination is Most Dangerous
The combination of ALT/AST ≥3× ULN with total bilirubin ≥2× ULN (without significant cholestatic abnormality) carries approximately 10% mortality risk and mandates immediate discontinuation. 2 This pattern indicates severe hepatocellular injury with impaired hepatic function 2.
Monitoring Strategy
Baseline liver function tests should be obtained before starting terbinafine 4, 1. However, routine periodic monitoring during treatment is not universally recommended, as symptomatic presentation typically precedes laboratory detection 3. Patient education about warning symptoms is more critical than routine laboratory monitoring 1, 3.
What to Tell Patients
Instruct patients to discontinue terbinafine immediately and seek medical attention if they develop persistent nausea, anorexia, fatigue, vomiting, right upper quadrant pain, jaundice, dark urine, or pale stools 1. These symptoms should prompt immediate liver function evaluation 1.