Have a High Threshold for Using Caspofungin and Voriconazole in Patients with Liver Disease

Have a High Threshold for Using Caspofungin and Voriconazole in Patients with Liver Disease

Leo Hsiao DO

Caspofungin is a member of a class of antifungals known as echinocandins. This family of antifungal exerts its effect by destabilizing the fungal cell wall through noncompetitive inhibition of β-(1,3)-D-glucan synthase. Inhibition of this enzyme prevents the synthesis of glucan, which is a key component of cell-wall stability. Not surprisingly, the relative amount of β-(1,3)-D-glucan making up the cell wall of various fungal species correlates to its susceptibility to caspofungin. Of note, caspofungin’s antifungal mechanism limits its activity to branch points where there is new cell-wall synthesis.

Caspofungin is effective against a wide range of fungi including Aspergillus species (fumigatus, flavus, terreus), Pneumocystis carinii, and Candida species. Its efficacy has been evaluated in the treatment of invasive candidiasis where caspofungin demonstrated a 74% success rate versus a 62% success rate of conventional therapy with amphotericin B. Because of limitations in formulation, caspofungin’s role in the treatment of oral or esophageal candidiasis should be limited either to patients who cannot tolerate azole therapy or to cases of documented failure to azole therapy. In the setting of empiric treatment of febrile neutropenia, caspofungin has been shown to be as effective as liposomal amphotericin B and with fewer side effects. Lastly, caspofungin was initially approved for salvage therapy for the management of invasive aspergillosis. Although there are some data to support its efficacy as primary therapy for invasive aspergillosis, there is concern that use of a fungistatic agent in immunocompromised patients might lead to relapse of disease.

Watch Out For

Common adverse reactions to caspofungin include fever, nausea, vomiting, and venous irritation. Caspofungin has also been shown to cause rash, bronchoconstriction, wheezing, and facial edema and flushing, denoting a probable correlation to histamine release. Alterations in liver function tests are mostly transient; however, in a patient with moderate pre-existing liver disease, defined as a Child-Pugh score of 7 to 9, dosage adjustments should be instituted. Since there are no good
data available to support the safety of caspofungin in patients with Child-Pugh scores >9, it may prudent to limit the use of caspofungin in this patient population. Also, because caspofungin is metabolized by N-acetylation in the liver, its use in cirrhotic patients potentially lacking this essential metabolic pathway should be judicious.

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Jul 1, 2016 | Posted by in ANESTHESIA | Comments Off on Have a High Threshold for Using Caspofungin and Voriconazole in Patients with Liver Disease
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