Is Augmentin (amoxicillin-clavulanate) dosed based on hepatic function?

From the Guidelines

Augmentin does require hepatic dosing adjustments, particularly in patients with severe hepatic dysfunction, where a reduction in dosage is recommended. When considering the management of patients with hepatic impairment, it's crucial to understand that clavulanic acid, a component of Augmentin, is primarily metabolized by the liver 1. This means that in cases of severe hepatic dysfunction, the clearance of clavulanic acid decreases, potentially leading to its accumulation and an increased risk of side effects.

Key Considerations

• The amoxicillin component of Augmentin is primarily eliminated by the kidneys and is less affected by liver dysfunction.
• Monitoring liver function tests is advisable when using Augmentin in patients with known hepatic impairment.
• Patients with both hepatic and renal impairment may require more significant dose adjustments as both elimination pathways are affected.
• Assessing liver function before prescribing Augmentin to patients with known liver disease is essential to determine the appropriate dosing strategy. Given the potential for hepatic impairment to affect the metabolism of clavulanic acid, dose adjustment is necessary to prevent adverse effects, and the approach should be tailored to the individual's degree of hepatic dysfunction, as suggested by guidelines such as those for managing patients with severe conditions 1.

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.

Hepatic Dosing: The FDA drug label recommends monitoring hepatic function at regular intervals in patients with hepatic impairment, but it does not provide specific dosing recommendations for hepatic impairment.

• Key Point: Hepatic function should be monitored, but the label does not explicitly state that the drug is hepatically dosed.
• Clinical Decision: Augmentin may require caution in patients with hepatic impairment, but the label does not provide clear guidance on hepatic dosing 2.

From the Research

Hepatic Dosing of Augmentin

• Augmentin, a combination of amoxicillin and clavulanate, is commonly used to treat bacterial infections.
• The studies provided do not directly address the hepatic dosing of Augmentin 3, 4, 5, 6, 7.
• However, it is known that amoxicillin-clavulanate is metabolized in the liver and can cause hepatotoxicity in rare cases 7.
• According to the study on hepatotoxicity of antibiotics and antifungals, amoxicillin-clavulanate is the most common cause of drug-induced liver injury (DILI) in the Western World 7.
• The study on dose adjustment in patients with liver disease suggests that drugs with a high hepatic extraction, such as amoxicillin, may require dose reduction in patients with liver disease 3.
• Another study on pharmacokinetics and dosage adjustment in patients with hepatic dysfunction notes that liver dysfunction can affect the pharmacokinetics of drugs, including those eliminated by hepatic metabolism or biliary excretion 5.
• However, there is no specific guidance on the hepatic dosing of Augmentin in the provided studies.
• It is recommended to consult the FDA-approved product label or a tertiary clinical reference, such as Micromedex, for guidance on dosing Augmentin in patients with hepatic impairment 6.