What is the effect of erythromycin (a macrolide antibiotic) on the liver?

From the Guidelines

Erythromycin should be used with caution in patients with liver disease, as it can cause elevated liver enzymes and rarely lead to cholestatic hepatitis, and the estolate form carries a higher risk of liver problems compared to other formulations 1. When considering the use of erythromycin in patients with liver disease, it is essential to weigh the potential benefits against the risks of liver toxicity.

• Erythromycin is metabolized primarily by the liver, which means patients with hepatic impairment may experience higher blood levels of the drug and increased risk of side effects.
• The estolate form of erythromycin carries a higher risk of liver problems compared to other formulations like erythromycin base, ethylsuccinate, or stearate 1.
• Patients with pre-existing liver disease should receive lower doses of erythromycin, and liver function should be monitored during treatment.
• If a patient develops signs of liver dysfunction while taking erythromycin, they should contact their healthcare provider immediately and the medication should be discontinued. It is also important to consider potential drug interactions when using erythromycin, as it can inhibit the cytochrome P450 enzyme system and increase the risk of adverse effects with certain medications 1.
• Erythromycin can interact with a variety of drugs, including alfentanil, bromocriptine, cyclosporine, and others, which can increase the risk of adverse effects.
• Patients taking erythromycin should be closely monitored for signs of liver toxicity and other adverse effects, and the medication should be discontinued if necessary.

From the FDA Drug Label

WARNINGS Hepatotoxicity There have been reports of hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, occurring in patients receiving oral erythromycin products. ADVERSE REACTIONS The most frequent side effects of oral erythromycin preparations are gastrointestinal and are dose-related. They include nausea, vomiting, abdominal pain, diarrhea and anorexia. Symptoms of hepatitis, hepatic dysfunction and/or abnormal liver function test results may occur (see WARNINGS) CLINICAL PHARMACOLOGY ...In the presence of normal hepatic function, erythromycin is concentrated in the liver and is excreted in the bile; the effect of hepatic dysfunction on biliary excretion of erythromycin is not known.

Erythromycin and Liver: Erythromycin has been associated with hepatotoxicity, including hepatic dysfunction, increased liver enzymes, and hepatocellular and/or cholestatic hepatitis.

• Key Points:
  • Hepatotoxicity has been reported in patients receiving oral erythromycin products.
  • Symptoms of hepatitis, hepatic dysfunction, and/or abnormal liver function test results may occur.
  • Erythromycin is concentrated in the liver and excreted in the bile in the presence of normal hepatic function.
  • The effect of hepatic dysfunction on biliary excretion of erythromycin is not known. 2 2 2

From the Research

Erythromycin and Liver Injury

• Erythromycin, a macrolide antibiotic, has been associated with liver injury, although the evidence is limited compared to other macrolides like azithromycin and clarithromycin 3, 4.
• A study on the pharmacokinetics of erythromycin in patients with severe cirrhosis found that the drug's metabolism is impaired in these patients, leading to increased serum concentrations of unbound erythromycin 5.
• Antibiotics, including erythromycin, are a common cause of drug-induced liver injury (DILI), which can be difficult to diagnose and may have severe consequences 6, 7.
• The clinical features of antibiotic-induced liver toxicity, including erythromycin, can vary widely and may include hepatitis-like damage, cholestatic/mixed type damage, and idiosyncratic reactions 7.
• Causality assessment of suspected DILI related to erythromycin can be challenging, particularly because some cases may occur long after the drug has been stopped 7.

Mechanisms and Risk Factors

• The mechanisms of erythromycin-induced liver injury are not fully understood, but may involve idiosyncratic reactions and genetic predisposition 7.
• Patients with pre-existing liver disease, such as cirrhosis, may be at increased risk of liver injury from erythromycin due to impaired drug metabolism 5.
• The relative risk of antibiotic-related hepatotoxicity, including erythromycin, is low, but the widespread prescription of these drugs means that they are a common cause of DILI 7.

Clinical Features and Diagnosis

• The clinical features of erythromycin-induced liver injury can include elevated liver enzymes, jaundice, and abdominal pain 3, 4.
• Diagnosis of DILI related to erythromycin requires a careful assessment of the patient's medical history, laboratory results, and imaging studies 6, 7.
• A temporal relationship between erythromycin use and the onset of liver injury is an important factor in diagnosing DILI 3, 4.