From the FDA Drug Label
The spectrum of these hepatic reactions has ranged from mild transient elevations in transaminases to clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in fluconazole-treated patients in clinical trials.
The frequency of liver function test monitoring in fluconazole therapy is not explicitly stated in the provided drug label. However, given the rare but serious hepatic reactions associated with fluconazole, it is reasonable to consider regular monitoring of liver function tests as a precautionary measure, especially in patients with underlying medical conditions or those taking concomitant medications known to be hepatotoxic 1.
- Key points:
- Rare but serious hepatic reactions have been reported with fluconazole.
- The overall rate of serum transaminase elevations was approximately 1% in clinical trials.
- Patients with underlying medical conditions or taking concomitant hepatotoxic medications may require closer monitoring.
From the Research
Liver function tests (LFTs) should be monitored at baseline before starting fluconazole therapy and then periodically during treatment, with more frequent monitoring for patients on long-term therapy or those with risk factors for hepatotoxicity, as supported by the most recent study 2.
Monitoring Frequency
For most patients on short-term fluconazole therapy (less than 2 weeks), monitoring LFTs at baseline and at the end of treatment may be sufficient.
- For patients on longer courses, monitoring every 2-4 weeks during the first 3 months of treatment and then every 1-3 months thereafter is generally recommended.
- More frequent monitoring (weekly or biweekly) is advised for patients with pre-existing liver disease, those taking other hepatotoxic medications, or those showing symptoms of liver dysfunction.
Risk of Hepatotoxicity
Fluconazole can cause hepatotoxicity in approximately 1-5% of patients, ranging from mild, asymptomatic elevations in liver enzymes to severe hepatitis, as reported in 2.
- The risk increases with higher doses, longer duration of therapy, and in patients with underlying liver disease.
- Pre-existing chronic liver disease increases the risk of azole-induced liver injury, with a hazard ratio of 4.68 for aminotransferases >200 U/L and 5.62 for severe acute liver injury, as found in 2.
Management of LFT Abnormalities
If significant LFT abnormalities develop (typically defined as greater than 3-5 times the upper limit of normal), dose reduction or discontinuation of fluconazole should be considered, depending on the clinical situation and the severity of the abnormalities, as suggested by 3 and 2.
Special Considerations
- Patients with cirrhosis or septic shock are at higher risk of meeting the Drug-Induced Liver Injury Network (DILIN) criteria, with odds ratios of 4.84 and 4.56, respectively, as reported in 4.
- Weight-based fluconazole dosing did not affect the number of critically ill recipients who met DILIN criteria, as found in 4.