Is Co-amoxiclav (amoxicillin/clavulanic acid) safe in patients with liver disease?

From the Guidelines

Co-amoxiclav should be used with caution in patients with liver disease due to its association with a high rate of drug-induced liver injury (DILI) 1. When considering the use of Co-amoxiclav in patients with liver disease, it is essential to weigh the potential benefits against the risks. According to the EASL clinical practice guidelines for the management of patients with decompensated cirrhosis, amoxicillin/clavulanic acid has been shown to have similar results to cefotaxime in terms of SBP resolution and mortality, but its use is associated with a higher risk of DILI 1. Some key points to consider when using Co-amoxiclav in patients with liver disease include:

• The risk of DILI is higher in patients with pre-existing liver conditions, elderly patients, and those with prolonged treatment courses 1.
• Liver function tests should be monitored before and during treatment with Co-amoxiclav.
• Alternative antibiotics with less hepatic metabolism might be preferable depending on the infection being treated.
• Patients with liver disease should inform their healthcare provider about their condition before starting Co-amoxiclav. It is crucial to note that the landscape of bacterial resistance is continuously changing, and the choice of empirical antibiotic treatment should be based on the severity of infection, local resistance profiles, and the environment of the infection 1. In patients with advanced cirrhosis, the risk of infections caused by multi-drug resistant organisms (MDROs) is higher, and the choice of antibiotic should take this into account 1. Overall, while Co-amoxiclav can be used in patients with liver disease, it is essential to use it with caution and carefully monitor liver function to minimize the risk of DILI.

From the FDA Drug Label

1. 2 Hepatic Dysfunction Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of amoxicillin and clavulanate potassium. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.

Liver: Hepatic dysfunction, including hepatitis and cholestatic jaundice, increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with amoxicillin and clavulanate potassium. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. Deaths have been reported [see Contraindications (4. 2), Warnings and Precautions (5. 2)].

4.2 Cholestatic Jaundice/Hepatic Dysfunction Amoxicillin and clavulanate potassium tablets are contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium tablets.

Co-amoxiclav is not recommended for patients with a history of hepatic dysfunction or cholestatic jaundice associated with its use 2, 2, 2.

• Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
• Contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium tablets.

From the Research

Co-amoxiclav and Liver Disease

• Co-amoxiclav is a combination of amoxicillin and clavulanic acid, and its use in patients with liver disease requires careful consideration 3, 4, 5.
• Studies have shown that liver damage associated with co-amoxiclav is more frequent in patients over the age of 50 and during long-term treatment, mainly due to the clavulanic acid component 6.
• A historical cohort study found that the adjusted estimate of the rate ratio for acute liver injury was 6.2 (CI 95% 1.3-29.7) among users of co-amoxiclav, suggesting a potential increased risk of hepatotoxicity 7.

Dose Adjustment in Liver Disease

• In patients with liver disease, dose adjustment of co-amoxiclav may be necessary to avoid excessive plasma drug concentrations and adverse effects 4, 5.
• The extent of hepatic extraction of co-amoxiclav should be considered when adjusting the dose, as well as the potential for impaired renal function in cirrhotic patients 5.
• Clinical monitoring of pharmacological effects and toxicity is important when using co-amoxiclav in patients with liver disease 5.

Precautions and Recommendations

• Co-amoxiclav should be used with caution in patients with liver disease, especially in those with advanced liver disease or cirrhosis 4, 6.
• The combination of amoxicillin and clavulanic acid should be reserved for infections due to bacteria that are resistant to amoxicillin, and alternative treatments should be considered when possible 6.
• Patients with liver disease should be closely monitored for signs of liver damage or adverse effects when taking co-amoxiclav 7, 6.