Can azithromycin (a macrolide antibiotic) cause transaminitis (elevated liver enzymes)?

Azithromycin and Transaminitis

Yes, azithromycin can cause transaminitis (elevated liver enzymes), with hepatotoxicity being a recognized adverse effect that ranges from mild transaminase elevations to severe cholestatic hepatitis. 1, 2

Mechanism and Presentation

• Azithromycin-induced liver injury typically occurs within 1-3 weeks after starting the medication, with most cases presenting 9-20 days after initiation 3
• The pattern of liver injury can be:
  • Hepatocellular (most common, ~55% of cases) 3
  • Cholestatic (33% of cases) 3
  • Mixed pattern (11% of cases) 3
• Clinical presentations include jaundice, abdominal pain, nausea, pruritus, and elevated liver enzymes 4, 3

Risk Factors and Monitoring

• Patients with pre-existing liver disease are at higher risk for azithromycin-induced hepatotoxicity 2
• Baseline liver function tests should be obtained before starting azithromycin in patients with known liver disease 2
• More frequent liver function monitoring is recommended for patients with underlying liver disease who require azithromycin 2
• The typical duration of azithromycin treatment associated with hepatotoxicity is relatively short (median 4 days, range 2-7 days) 3

Clinical Course and Outcomes

• Most patients with azithromycin-induced liver injury recover fully after discontinuation of the medication 3
• However, serious complications can occur, including:
  • Chronic liver injury (22% of cases) 3
  • Severe hypersensitivity cutaneous reactions 3
  • Rare cases of death or need for liver transplantation, particularly in patients with underlying chronic liver disease 3

Management

• Prompt discontinuation of azithromycin if signs of liver injury develop 4, 5
• Monitor liver function tests until normalization 2
• For patients with severe or unstable liver disease, consider alternative antibiotics with minimal hepatic metabolism 2
• Azithromycin is contraindicated in patients with a history of cholestatic jaundice or hepatic dysfunction associated with previous use of the drug 2

Clinical Pearls

• Liver injury may not be immediately apparent during the course of azithromycin treatment, as abnormal liver tests are often first detected approximately 2 weeks after azithromycin cessation 3
• The mean peak levels in documented cases include ALT of 2127 IU/L, alkaline phosphatase of 481 IU/L, and total bilirubin of 9.2 mg/dL 3
• Azithromycin-induced liver injury can occur even in pregnant women, potentially mimicking intrahepatic cholestasis of pregnancy 6
• Histologic features may include ductopenia and veno-occlusive changes in some patients 3

While azithromycin is generally considered safer than other macrolides regarding hepatotoxicity, clinicians should remain vigilant about the potential for liver injury, particularly in patients with pre-existing liver disease or those taking other hepatotoxic medications.