Does metronidazole increase liver enzymes, specifically causing hypertransaminasemia?

From the Guidelines

Metronidazole can increase liver enzymes, as evidenced by studies showing transient elevations in liver enzymes such as ALT, AST, and alkaline phosphatase in some patients, with the largest and longest clinical trial on the use of antibiotics in PSC demonstrating a 23% reduction in ALP with metronidazole treatment 1.

Key Points to Consider

• Metronidazole is metabolized in the liver, which explains its potential hepatic effects.
• Patients with pre-existing liver disease may be at higher risk for this side effect and might require dose adjustments or closer monitoring.
• The liver enzyme increases usually resolve after discontinuation of the drug.
• While taking metronidazole, it's essential to avoid alcohol completely as the combination can cause severe reactions including further liver stress.
• If a patient develops symptoms like jaundice, dark urine, right upper quadrant pain, or unusual fatigue while taking metronidazole, they should contact their healthcare provider immediately as these could indicate more serious liver issues.

Monitoring and Management

• Liver enzymes and function should be assessed periodically during treatment with metronidazole.
• Treatment should be interrupted if transaminases are confirmed to be >5 times the ULN and discontinued in the event of liver injury.
• Post hoc analyses of clinical trial data demonstrated that elevations of liver enzymes and bilirubin did occur but were asymptomatic, transient, and generally resolved within 3 months without treatment discontinuation in patients treated with metronidazole 1.

From the FDA Drug Label

Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. At very high dose levels (approx 500 mg/kg/day which is approximately 33 times the most frequently recommended human dose for a 50 kg adult based on mg/kg body weight) there was a statistically significant increase in the incidence of malignant liver tumors in males

The drug label does indicate that metronidazole may interfere with liver enzyme tests, such as AST and ALT. However, it does not directly state that metronidazole increases liver enzymes.

• The label mentions that high doses of metronidazole were associated with an increased incidence of malignant liver tumors in animal studies 2.
• But this is not the same as an increase in liver enzymes. Therefore, based on the information provided, it cannot be concluded that metronidazole increases liver enzymes.

From the Research

Metronidazole and Liver Enzymes

• The effect of metronidazole on liver enzymes is not directly addressed in the study 3, which focuses on vancomycin-induced elevation of liver enzyme levels.
• However, studies 4 and 5 suggest that metronidazole may have a beneficial effect on reducing liver enzyme abnormalities, particularly in the context of total parenteral nutrition (TPN).
• In the study 4, metronidazole administration decreased hepatic lipid content in rats receiving TPN, but did not significantly affect liver enzyme levels.
• The study 5 found that metronidazole prevention was associated with the prevention of the expected rise of serum alkaline phosphatase, gamma glutamyl transpeptidase, and aspartate amino-transferase in patients receiving TPN.
• In contrast, the study 6 suggests that metronidazole may induce liver injury, as evidenced by increased liver enzymes (ALT and AST) and histopathological examination, although this effect was mitigated by turmeric supplementation.
• The study 7 found that metronidazole disposition was altered in patients with liver failure, with decreased systemic clearance and prolonged elimination half-life, but did not directly address the effect of metronidazole on liver enzymes 7.