Does Ceftriaxone (Rocephin) cause liver dysfunction?

From the Guidelines

Rocephin (ceftriaxone) can occasionally cause liver dysfunction, though it's not among the most common side effects. This third-generation cephalosporin antibiotic has been associated with transient elevations in liver enzymes in approximately 1-3% of patients. More serious liver injury is rare but can include cholestatic hepatitis (inflammation of the liver with bile flow obstruction). The mechanism involves the formation of calcium-ceftriaxone precipitates in the biliary system, which can lead to biliary sludge or pseudolithiasis (false stones) 1. Patients with pre-existing liver disease, those receiving high doses, or those on prolonged therapy may be at higher risk. Liver function typically normalizes after discontinuation of the medication. Healthcare providers often monitor liver function tests in patients on extended Rocephin therapy, especially those with risk factors. If a patient develops symptoms like jaundice, dark urine, right upper quadrant pain, or abnormal liver tests while taking Rocephin, they should contact their healthcare provider promptly.

Some key points to consider:

• The use of ceftriaxone in patients with liver disease requires careful monitoring, as it may exacerbate existing liver conditions 1.
• The risk of liver dysfunction is higher in patients with pre-existing liver disease, those receiving high doses, or those on prolonged therapy.
• Ceftriaxone is still a recommended antibiotic for certain conditions, such as spontaneous bacterial peritonitis, in patients with cirrhosis 1.
• The benefits of using ceftriaxone in these cases often outweigh the risks, but close monitoring of liver function is essential.

In terms of management, the following steps can be taken:

• Monitor liver function tests regularly in patients on extended Rocephin therapy, especially those with risk factors.
• Adjust the dose or discontinue the medication if liver dysfunction occurs.
• Consider alternative antibiotics if the patient has a history of liver disease or is at high risk of liver dysfunction.
• Educate patients on the signs and symptoms of liver dysfunction and the importance of seeking medical attention if they occur.

From the FDA Drug Label

Dosage adjustments should not be necessary in 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. In patients with both severe renal and hepatic dysfunction, close clinical monitoring for safety and efficacy is advised.

Rocephin (ceftriaxone) and liver dysfunction:

• The FDA drug label does not directly state that Rocephin causes liver dysfunction.
• However, it does mention that dosage adjustments are not necessary in patients with hepatic dysfunction alone.
• Caution is advised in patients with both hepatic dysfunction and significant renal disease.
• Close clinical monitoring is recommended in patients with both severe renal and hepatic dysfunction 2, 3.

From the Research

Rocephin and Liver Dysfunction

• Rocephin, also known as ceftriaxone, is a third-generation cephalosporin antibiotic that has been associated with liver dysfunction in some cases 4, 5, 6.
• Studies have shown that high-dose ceftriaxone (4g/day) is independently associated with liver injury, with an odds ratio of 7.23 (95% CI 2.01-26.0) compared to normal-dose ceftriaxone (2g/day) 4.
• A retrospective study found that ceftriaxone-induced liver injury occurred in 19.7% of patients when used in combination with other medications that are metabolized in the liver 5.
• Another study reported a case of acute liver injury induced by ceftriaxone, which was confirmed by the RUCAM score 6.
• However, a dual-centre retrospective observational analysis found that the incidence of elevated liver enzymes did not clearly correlate with ceftriaxone dosing, with 10.6% and 5.1% of patients experiencing elevated liver enzymes in the 2g and 4g groups, respectively 7.

Risk Factors for Liver Dysfunction

• High-dose ceftriaxone (4g/day) has been identified as a risk factor for liver injury 4, 5.
• Combination with other medications that are metabolized in the liver may also increase the risk of liver injury 5.
• Pre-existing liver disease may affect the disposition of ceftriaxone, with decreased non-renal clearance of unbound drug in patients with chronic liver disease 8.

Monitoring and Management

• Clinicians should carefully observe for signs of liver injury after high-dose ceftriaxone use 4.
• Monitoring of liver function and full blood count is indicated in patients receiving prolonged ceftriaxone therapy, regardless of dosing 7.
• Treatment cessation due to adverse effects, including liver dysfunction, should be considered if necessary 7.