From the Guidelines
Amphotericin B can cause liver function test (LFT) derangements, and management depends on the severity of the elevations, with options including continued monitoring, dose reduction, or switching to a lipid formulation like liposomal amphotericin B (AmBisome) 1.
Key Considerations
- Amphotericin B-induced LFT derangements typically manifest as elevated transaminases (AST, ALT), alkaline phosphatase, and occasionally bilirubin.
- For mild to moderate elevations (less than 3-5 times the upper limit of normal), continued monitoring without dose adjustment may be sufficient while maintaining close observation.
- For more severe elevations, consider temporarily reducing the amphotericin dose or switching to a lipid formulation such as liposomal amphotericin B (AmBisome), which has a better hepatic safety profile at doses of 3-5 mg/kg/day 1.
- If LFT abnormalities persist or worsen, consultation with hepatology and infectious disease specialists is warranted, and alternative antifungal agents like echinocandins (caspofungin, micafungin) or azoles (if the infection is susceptible) should be considered.
Mechanism and Monitoring
- The mechanism behind amphotericin's hepatotoxicity relates to its direct membrane-damaging effects on hepatocytes and potential immune-mediated injury.
- Regular monitoring of liver function (twice weekly initially, then weekly) is essential during amphotericin therapy, along with renal function tests and electrolytes, as amphotericin can cause multiple organ toxicities simultaneously 1.
Alternative Formulations and Agents
- Lipid formulations of amphotericin B, such as liposomal amphotericin B (AmBisome), have a role among patients who are intolerant of conventional amphotericin B or are at high risk for nephrotoxicity 1.
- Alternative antifungal agents like echinocandins (caspofungin, micafungin) or azoles (if the infection is susceptible) should be considered if LFT abnormalities persist or worsen 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Amphotericin Induced LFT Derangement
- Amphotericin B formulations may cause hepatic toxicity, ranging from mild and asymptomatic abnormalities in liver function tests to substantial liver injury and fulminant hepatic failure 2.
- A case report suggests that amphotericin B-induced hepatotoxicity is possible, with elevation of liver enzymes after the addition of amphotericin B to initial itraconazole therapy, which resolved rapidly with discontinuation of amphotericin B 3.
- The mechanism of action of amphotericin B and its potential interaction with other hepatotoxic agents, such as azole antifungal drugs, may contribute to hepatotoxicity 3.
- Abnormal liver function tests can be caused by various factors, including drug-induced liver injury, and a thorough understanding of the distribution, metabolism, elimination, and drug-drug interactions of antifungal agents is necessary to guide their use in patients at high risk for hepatic dysfunction 2, 4.
- Comprehensive diagnostic evaluation is essential to identify the underlying etiology of abnormal liver function tests and to initiate appropriate therapeutic strategies 4.