Is Augmentin (Amoxicillin/Clavulanate) safe in liver failure?

From the Guidelines

Augmentin (Amoxicillin/Clavulanate) is generally safe in liver failure, as it has been used as an alternative to cefotaxime in patients with spontaneous bacterial peritonitis (SBP) in cirrhosis, with similar results in terms of infection resolution and mortality 1.

Key Points

• The dose of amoxicillin/clavulanic acid used in the study was 1/0.2 g/8h IV followed by 0.5/0.125 g/8h PO 1.
• The use of amoxicillin/clavulanic acid in liver failure is supported by guidelines for the management of community-acquired pneumonia, which recommend its use in patients with comorbidities such as liver disease 1.
• However, it is essential to note that the evidence is not extensive, and the study that compared amoxicillin/clavulanic acid to cefotaxime had a small sample size, so results should be confirmed in larger trials 1.

Clinical Considerations

• In patients with liver failure, it is crucial to monitor for signs of infection and to initiate empirical antibiotic therapy promptly, as delayed treatment can lead to poor outcomes.
• The choice of antibiotic should be based on the suspected causative organisms and the patient's underlying condition, including the presence of comorbidities such as liver disease.
• Amoxicillin/clavulanic acid is a reasonable option for patients with liver failure, but its use should be guided by clinical judgment and careful monitoring of the patient's response to treatment.

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)]

Augmentin (Amoxicillin/Clavulanate) use in liver failure is associated with a risk of hepatic dysfunction, including hepatitis and cholestatic jaundice.

• Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
• The hepatic dysfunction may be severe and is usually reversible, but deaths have been reported 2, 2. It is recommended to use Augmentin with caution in patients with liver failure and to monitor hepatic function regularly.

From the Research

Safety of Augmentin in Liver Failure

• The safety of Augmentin (Amoxicillin/Clavulanate) in liver failure is a concern due to reports of adverse hepatic reactions, including cholestatic illness, hepatic failure, and Stevens-Johnson syndrome 3, 4, 5, 6, 7.
• Studies have shown that Augmentin can cause hepatotoxicity, with symptoms appearing up to six weeks after stopping therapy 4, 5, 6.
• The mechanism of Augmentin-induced hepatotoxicity is thought to be a hypersensitivity reaction to clavulanic acid 5.
• Cases of acute liver failure due to amoxicillin and amoxicillin/clavulanate have been reported, with some patients requiring liver transplantation 6.
• Delayed presentation of drug-induced hepatic injury is possible, with one case report describing a 20-year-old female who presented with severe cholestatic hepatitis caused by amoxicillin-clavulanate several weeks after treatment 7.

Hepatotoxicity and Liver Failure

• Hepatotoxicity associated with Augmentin can range from mild to severe, with some cases progressing to liver failure 3, 4, 6.
• Cholestatic hepatitis is a common presentation of Augmentin-induced hepatotoxicity, with symptoms including jaundice, pruritus, and fatigue 4, 5, 7.
• In severe cases, Augmentin-induced hepatotoxicity can lead to Stevens-Johnson syndrome, a life-threatening condition characterized by skin and mucous membrane lesions 4.

Clinical Implications

• Clinicians should be aware of the potential for Augmentin to cause hepatotoxicity and monitor patients for signs and symptoms of liver injury, particularly in the weeks following treatment 4, 5, 6.
• Early recognition and treatment of Augmentin-induced hepatotoxicity are crucial to preventing progression to liver failure and improving patient outcomes 6, 7.