Voriconazole and the liver

Abstract

Voriconazole is an azole useful for the prophylaxis and the treatment of aspergillosis and other fungal infections in immunosuppressed subjects, as those found in aplasia after aggressive polychemotherapy treatments, after hematopoietic stem cell, liver or lung transplantation. Its administration in therapeutic doses lead to extremely varied serum levels from patient to patient and even to the same patient. The explanations are varied: nonlinear pharmacokinetics, certain patient-related factors, including genetic polymorphisms in the cytochrome P450 2C19 gene, the kidney and liver function, simultaneous administration with other drugs metabolised by the same cytochrome. It is recommended to maintain the serum concentrations of voriconazole between 1.5 and 4 μg/mL. At lower values its efficacy decreases and at higher values the risk of neurological toxicity increases. Even at these concentrations it is not excluded the possible appearance of a variety of toxic effects, including on the liver, manifested by cholestasis, hepatocytolisis, or their combination. It is recommended to monitor the clinical and laboratory evolution of all patients treated with voriconazole, and of the serum levels of the drug of those who belong to risk groups, even if there is still no consensus on this issue, given the lack of correlation between the serum level and the occurrence of adverse effects in many patients.

COVID-19 Syndemic: Convergence of COVID-19, Pulmonary Aspergillosis (CAPA), Pulmonary Tuberculosis, Type 2 Diabetes Mellitus, and Arterial Hypertension

“…Two of the patients survived and are in therapy with anti-Mtb DOTS, voriconazole treatment for aspergillosis, and treatments for their concomitant diseases with drugs provided by the Mexican public health system. They are also under control, with liver enzymatic testing and electrocardiography because of the possible deleterious side effects of anti-Mtb and voriconazole treatment, such as drug hepatitis damage or long QT syndrome [ 41 ]. Regarding our third patient, who did not survive, a male 31-year-old, he was the youngest of the studied patients, but it is unclear why he died.…”

Voriconazole-Induced Acute Liver Injury: A Case Report

“…Most authors suggest a steady-state serum voriconazole concentration between 1.5 and 4 μg/mL. A correlation between the drug concentration and higher serum levels of serum alkaline phosphatase, aspartate aminotransferase, and bilirubin was found [ 10 ].…”

Generalized exfoliative skin rash as an early predictor of supratherapeutic voriconazole trough levels in a leukemic child: A case report

“…The worsening of the liver function tests can observe even after at least four doses of VCZ in patients with preexisting severe liver dysfunction. Notably, this phenomenon occurs in patients who have received a higher initial dose of VCZ [ 31 ].…”