Are there concerns with using amoxicillin (amoxicillin) and fluconazole (fluconazole) in a patient with fatty liver disease (steatosis)?

From the Guidelines

Both amoxicillin and fluconazole can be used in patients with fatty liver disease, but caution and monitoring of liver function are advised, especially with fluconazole due to its partial liver metabolism. When considering the management of metabolic dysfunction-associated steatotic liver disease (MASLD), as outlined in the recent clinical practice guidelines 1, it's crucial to approach the use of any medication with caution, taking into account the potential for compromised liver function.

For patients with fatty liver disease, amoxicillin, which is primarily eliminated by the kidneys, is generally well-tolerated and can be used at standard doses unless there's evidence of significant liver dysfunction. However, fluconazole, being metabolized partially by the liver, warrants closer monitoring of liver function during treatment, particularly for longer courses.

Key considerations include:

• Monitoring liver function tests (LFTs) before and during treatment with fluconazole
• Adjusting doses of fluconazole if there's evidence of impaired liver function, such as elevated liver enzymes, low albumin, or prolonged prothrombin time
• Advising patients to report any new symptoms suggestive of liver injury, such as jaundice, severe abdominal pain, unusual fatigue, or dark urine
• Recognizing that fatty liver disease may already have compromised liver function, potentially increasing the risk of drug-induced liver injury with medications like fluconazole

Given the guidance from the EASL-EASD-EASO clinical practice guidelines on the management of MASLD 1, the focus should be on careful management and monitoring, rather than outright avoidance of these medications, unless specific contraindications exist. The primary concern is balancing the need for effective treatment of the underlying condition with the potential risks associated with liver dysfunction in patients with fatty liver disease.

From the FDA Drug Label

Fluconazole should be administered with caution to patients with liver dysfunction. Fluconazole has been associated with rare cases of serious hepatic toxicity, including fatalities primarily in patients with serious underlying medical conditions Hepato-biliary: In combined clinical trials and marketing experience, there have been rare cases of serious hepatic reactions during treatment with fluconazole.

There are concerns for fatty liver with fluconazole, as it has been associated with rare cases of serious hepatic toxicity. However, there is no information about amoxicillin in the provided drug labels.

• Fluconazole should be administered with caution to patients with liver dysfunction 2.
• The hepatic reactions have ranged from mild transient elevations in transaminases to clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities 2.

From the Research

Fatty Liver Concerns with Amoxicillin and Fluconazole

• There are concerns regarding the use of certain medications in patients with fatty liver disease, including amoxicillin and fluconazole.
• A study published in 1994 3 reported a case of fluconazole worsening liver dysfunction in a patient with hepatitis, highlighting the need for liver function monitoring during fluconazole therapy.
• Another study from 2010 4 found that amoxicillin-clavulanate is one of the most common causes of drug-induced liver injury (DILI) and hepatotoxicity, particularly in patients with underlying liver disease.
• The same study 4 noted that the severity of antibiotic-induced DILI varies widely and can be influenced by age, with hepatitis-like damage tend to be more severe than cholestatic/mixed type.

Liver Disease and Medication Use

• A review article from 2013 5 provided a practical guide for prescribing medications in patients with cirrhosis, emphasizing the need for caution when using certain drugs, such as NSAIDs, and recommending lower doses or reduced dosing frequency due to altered pharmacokinetics.
• The article 5 also highlighted the importance of avoiding drugs that can precipitate renal failure, gastrointestinal bleeding, spontaneous bacterial peritonitis, and encephalopathy in patients with cirrhosis.

Fatty Liver Disease Overview

• Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of 25% and is a leading cause of cirrhosis and hepatocellular carcinoma, as reported in a 2021 study 6.
• NAFLD is characterized by a disease continuum from steatosis to non-alcoholic steatohepatitis (NASH), with advanced liver fibrosis being a key prognostic marker for liver-related outcomes and overall mortality.
• Lifestyle changes, including physical activity, are crucial for the prevention and treatment of NAFLD, as noted in a 2021 study 7, which identified perceived barriers to physical activity, such as lack of exercise resources and education, physical discomfort, and time constraints.