Can Ceftriaxone (Rocephin) and Azithromycin (Zithromax) affect liver enzymes?

From the Guidelines

Both Rocephin (ceftriaxone) and Zithromax (azithromycin) can affect liver enzymes, with Rocephin having a slightly higher risk of liver enzyme elevation, especially at higher doses or longer durations, as noted in various studies 1. When considering the impact of these antibiotics on liver enzymes, it's essential to weigh the benefits against the potential risks, particularly for patients with pre-existing liver disease or those taking other hepatotoxic medications.

• The mechanism of liver enzyme elevation involves either direct hepatocellular injury or cholestatic patterns where bile flow is affected.
• Patients at higher risk include those with pre-existing liver disease, those taking other hepatotoxic medications, or elderly patients.
• Monitoring of liver function is crucial, especially for extended treatment courses, and patients should be aware of symptoms such as yellowing of skin or eyes, dark urine, light-colored stools, unusual fatigue, or abdominal pain.
• According to the most recent guideline 1, baseline liver function tests should be measured before initiating macrolide therapy, such as azithromycin, and patients should be counselled about potential adverse effects, including gastrointestinal upset, hearing and balance disturbance, cardiac effects, and microbiological resistance.
• The British Thoracic Society guideline 1 also recommends a risk-benefit profile consideration in each individual if significant side effects from oral macrolide therapy develop, and treatment with azithromycin should be considered for a minimum of 6–12 months to assess evidence of efficacy in reducing exacerbations.

From the FDA Drug Label

Hepatotoxicity Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Adverse reactions related to hepatic dysfunction have been reported in postmarketing experience with azithromycin. Patients with hepatic dysfunction; however, in patients with both hepatic dysfunction and significant renal disease, caution should be exercised and the ceftriaxone dosage should not exceed 2 grams daily.

Rocephin (Ceftriaxone) and Zithromax (Azithromycin) can affect liver enzymes.

• Azithromycin has been associated with abnormal liver function, hepatitis, and hepatic failure.
• Ceftriaxone should be used with caution in patients with hepatic dysfunction, especially those with significant renal disease. 2 2 3

From the Research

Liver Enzyme Effects of Rocephin and Zithromax

• Rocephin (ceftriaxone) and Zithromax (azithromycin) are antibiotics that can be used to treat various infections.
• There is evidence to suggest that both drugs can affect liver enzymes, although the extent of this effect may vary.

Azithromycin's Effect on Liver Enzymes

• A case study published in 2010 4 reported a 69-year-old woman who developed cholestatic hepatitis after four days of therapy with high-dose azithromycin.
• Another study published in 2025 5 presented a case of Legionnaires' disease treated with azithromycin, complicated by elevated liver enzymes.
• These studies suggest that azithromycin can cause liver injury and elevate liver enzymes in some patients.

Ceftriaxone's Effect on Liver Enzymes

• A study published in 2022 6 found that elevated liver enzymes did not clearly correlate with ceftriaxone dosing, but monitoring of liver function is still indicated in patients receiving prolonged ceftriaxone therapy.
• This study suggests that ceftriaxone may affect liver enzymes, but the relationship between dosing and liver enzyme elevation is not clear.

Interaction Between Azithromycin and Ceftriaxone

• A study published in 2002 7 found that there is no pharmacokinetic interaction between azithromycin and ceftriaxone when they are administered concurrently.
• This study suggests that the combination of azithromycin and ceftriaxone is not likely to increase the risk of liver enzyme elevation due to a pharmacokinetic interaction.

General Considerations

• Both azithromycin and ceftriaxone can cause liver enzyme elevation, and monitoring of liver function is indicated in patients receiving these drugs, especially with prolonged therapy 6, 5.
• The risk of liver enzyme elevation may vary depending on the individual patient and the specific infection being treated.