Azacitidine and Liver Function Derangement
Yes, azacitidine can cause hepatotoxicity and liver function derangement, particularly in patients with severe pre-existing hepatic impairment, and is contraindicated in patients with advanced malignant hepatic tumors. 1
FDA-Mandated Warnings and Contraindications
The FDA label for azacitidine contains explicit warnings about hepatotoxicity:
Azacitidine is contraindicated in patients with advanced malignant hepatic tumors due to reports of progressive hepatic coma and death during treatment, especially in patients with baseline albumin <30 g/L 1
Liver chemistries must be monitored prior to initiation of therapy and with each treatment cycle 1
Azacitidine is "potentially hepatotoxic in patients with severe pre-existing hepatic impairment," requiring caution in patients with liver disease 1
Patients with extensive tumor burden from metastatic disease have experienced progressive hepatic coma and death during azacitidine treatment 1
Clinical Evidence of Hepatotoxicity
Fatal hepatic failure has been documented in clinical practice:
A case report described acute liver failure due to liver parenchymal infiltration with acute myelogenous leukemia in a patient receiving azacitidine, resulting in significant elevation of bilirubin and INR, worsening mental status, and rapid demise 2
Lethal toxicity after azacitidine administration has been reported, particularly in patients with impaired drug metabolism 3
Monitoring Requirements
The following monitoring protocol should be implemented:
Obtain baseline liver function tests (transaminases, bilirubin, albumin) before starting azacitidine 1
Check liver chemistries prior to each treatment cycle 1
Pay particular attention to patients with baseline albumin <30 g/L, as they are at highest risk for progressive hepatic complications 1
Monitor for signs of hepatic decompensation including elevated bilirubin, INR elevation, and altered mental status 2
Important Clinical Caveats
Key considerations for safe azacitidine use:
Safety and effectiveness in patients with MDS and hepatic impairment have not been established, as these patients were excluded from clinical trials 1
Azacitidine undergoes hepatic metabolism by cytidine deaminase (CDA), and patients with CDA deficiency (poor metabolizer phenotype) are at risk for severe or lethal toxicities 3, 4
The risk appears highest in patients with pre-existing liver disease, extensive tumor burden, or low albumin levels 1
One case demonstrated improvement of erythema nodosum after azacitidine treatment, suggesting variable effects on different organ systems 5
If liver function abnormalities develop during treatment, consider dose reduction or discontinuation based on severity, and investigate alternative causes of hepatotoxicity including disease progression, viral hepatitis, or other hepatotoxic medications.