From the Guidelines
For patients with deranged liver function tests (LFTs), echinocandins are the preferred antifungal medication option due to their favorable hepatic safety profile. The most recent and highest quality study 1 recommends the use of echinocandins, such as micafungin (150 mg daily), caspofungin (70-mg loading dose, then 50 mg daily), or anidulafungin (200 mg daily), for the treatment of candidiasis in patients with deranged LFTs. These medications undergo minimal hepatic metabolism and do not require dose adjustment in liver disease.
Key Considerations
- Fluconazole (400mg loading dose followed by 200-400mg daily) may also be considered in mild to moderate liver dysfunction, though dose reduction by 50% is recommended in severe hepatic impairment 1.
- Amphotericin B lipid formulations (3-5mg/kg/day) can be used regardless of liver function, though they carry risks of nephrotoxicity and infusion reactions 1.
- It's essential to avoid conventional azoles like voriconazole, itraconazole, and posaconazole in severe liver dysfunction as they undergo extensive hepatic metabolism and may further worsen liver function.
- Regular monitoring of LFTs during antifungal therapy is crucial, regardless of which agent is chosen.
- The selection of antifungal should also consider the specific fungal pathogen, infection site, drug interactions, and the patient's overall clinical condition.
Antifungal Options
- Echinocandins: micafungin, caspofungin, anidulafungin
- Fluconazole: with dose reduction in severe hepatic impairment
- Amphotericin B lipid formulations: with caution due to risks of nephrotoxicity and infusion reactions
- Avoid conventional azoles: voriconazole, itraconazole, posaconazole in severe liver dysfunction
From the FDA Drug Label
5.1 Hepatic Adverse Drug Reactions Hepatic adverse drug reactions (e.g., elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin) have been reported in clinical trials. The elevations in liver-related laboratory tests were generally reversible and did not require discontinuation of CRESEMBA Cases of more severe hepatic adverse drug reactions including hepatitis, cholestasis or hepatic failure including death have been reported in patients with serious underlying medical conditions (e.g., hematologic malignancy) during treatment with azole antifungal agents, including CRESEMBA. Evaluate liver-related laboratory tests at the start and during the course of CRESEMBA therapy. Monitor patients who develop abnormal liver-related laboratory tests during CRESEMBA therapy for the development of more severe hepatic injury Discontinue CRESEMBA if clinical signs and symptoms consistent with liver disease develop that may be attributable to CRESEMBA
Isavuconazonium sulfate (CRESEMBA) can be used in patients with deranged Liver Function Tests (LFTs), but it is essential to monitor liver-related laboratory tests at the start and during the course of therapy. If abnormal liver-related laboratory tests develop, patients should be monitored for the development of more severe hepatic injury, and CRESEMBA should be discontinued if clinical signs and symptoms consistent with liver disease develop. Posaconazole label does not provide direct information on its use in patients with deranged LFTs. Therefore, isavuconazonium sulfate (CRESEMBA) is a more suitable option for patients with deranged LFTs, with close monitoring of liver function. 2
From the Research
Antifungal Options for Patients with Deranged Liver Function Tests (LFTs)
- Patients with deranged LFTs require careful consideration when selecting antifungal medications, as some antifungals can exacerbate liver damage 3, 4, 5.
- Echinocandins, such as anidulafungin, are a suitable option for patients with liver dysfunction, as they are not metabolized by the liver and do not require dose adjustments 6.
- Azole antifungals, such as voriconazole, posaconazole, and isavuconazole, can cause hepatotoxicity and should be used with caution in patients with pre-existing liver disease 7.
- Monitoring of liver function tests is essential when using antifungal medications, especially in patients with deranged LFTs, to minimize the risk of hepatotoxicity 3, 5.
- Dosage adjustment of antifungal agents may be necessary in patients with varying degrees of hepatic impairment, and guidance on dosage adjustment can be found in the literature 4.
Specific Antifungal Medications
- Anidulafungin: suitable for patients with severe liver dysfunction, no dose adjustments required 6.
- Voriconazole: can cause hepatotoxicity, use with caution in patients with pre-existing liver disease 7.
- Posaconazole: can cause hepatotoxicity, use with caution in patients with pre-existing liver disease 7.
- Isavuconazole: can cause hepatotoxicity, use with caution in patients with pre-existing liver disease 7.
- Fluconazole: may be used as a prophylactic dose in patients with recovered liver function 7.