Can Biaxin (clarithromycin) and amoxicillin treatment for H. pylori cause elevation of liver enzymes in a patient with a history of hyperglycemia and iron deficiency anemia?

Can Clarithromycin (Biaxin) and Amoxicillin Cause Elevated Liver Enzymes?

Yes, both clarithromycin and amoxicillin can cause elevation of liver enzymes, with clarithromycin carrying a more significant hepatotoxic risk that includes potentially severe and even fatal hepatic dysfunction. 1

Clarithromycin Hepatotoxicity

The FDA drug label explicitly warns that clarithromycin causes hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice. 1 This hepatotoxicity may be severe and is usually reversible, but in some instances, hepatic failure with fatal outcome has been reported. 1

Key Clinical Features of Clarithromycin-Induced Liver Injury:

• Symptoms to monitor: anorexia, jaundice, dark urine, pruritus, or tender abdomen 1
• Action required: Discontinue clarithromycin immediately if signs and symptoms of hepatitis occur 1
• Severity: Generally associated with serious underlying diseases and/or concomitant medications 1

Drug Interaction Concerns:

Clarithromycin is a strong CYP3A4 inhibitor, which can lead to markedly increased transaminases when combined with certain medications like lomitapide. 1 This metabolic interaction pathway may amplify hepatotoxic effects in susceptible patients.

Amoxicillin Hepatotoxicity

Amoxicillin can cause hepatocellular liver injury with bile-duct damage, though this occurs at a very low rate. 2 A documented case demonstrated hepatocellular and bile-duct injury with elevated liver enzymes that resolved upon discontinuation of amoxicillin. 2

Recent prospective data from Iceland identified amoxicillin-clavulanate as one of the major causative agents in drug-induced liver injury (DILI) cases presenting with elevated liver enzymes. 3 While this study specifically examined the amoxicillin-clavulanate combination, it underscores amoxicillin's hepatotoxic potential.

Clinical Context: H. pylori Treatment and Iron Deficiency Anemia

The combination of clarithromycin and amoxicillin for H. pylori eradication has been studied extensively in patients with iron deficiency anemia. 4, 5, 6 These studies demonstrate successful H. pylori eradication and resolution of anemia without reporting significant hepatotoxicity, suggesting the combination is generally well-tolerated in this population. However, this does not eliminate the risk of liver enzyme elevation.

Practical Management Approach

When to Suspect Drug-Induced Liver Injury:

• Timing: Liver enzyme elevation typically occurs during or shortly after antibiotic therapy
• Pattern: Can present as hepatocellular (predominantly ALT/AST elevation) or cholestatic (predominantly ALP elevation with or without bilirubin) 2, 3
• Severity markers: ALT > 500 U/L or ALT > 250 U/L with ALP > 210 U/L warrant immediate evaluation 3

Critical Pitfall to Avoid:

Do not attribute all liver enzyme elevations to the patient's underlying conditions (hyperglycemia, iron deficiency anemia) without considering drug-induced hepatotoxicity. The hemochromatosis guidelines note that normalization of elevated liver enzymes occurs with phlebotomy treatment 7, but this is specific to iron overload-related hepatic injury, not drug-induced injury.

Immediate Actions if Hepatotoxicity Suspected:

1. Discontinue both antibiotics immediately 1, 2
2. Assess for symptoms: jaundice, dark urine, pruritus, abdominal tenderness, anorexia 1
3. Monitor liver enzymes serially to confirm downward trend after drug discontinuation 2
4. Evaluate for alternative causes: choledocholithiasis, ischemic hepatitis, viral hepatitis, or hepatobiliary malignancy 3

Expected Recovery:

Hepatic dysfunction from both clarithromycin and amoxicillin is usually reversible upon discontinuation, with liver enzyme levels reducing to near-normal range. 1, 2