Vfend Disease Interactions

Serious hepatic reactions (including clinical hepatitis, cholestasis, fulminant hepatic failure [including fatalities]) have been reported infrequently during voriconazole therapy. Hepatic reactions have primarily occurred in patients with serious underlying medical conditions (mainly hematological malignancy); however, some reactions (including hepatitis, jaundice) occurred in patients with no other identifiable risk factors. Hepatic function should be monitored in all patients; a higher frequency of liver enzyme elevations was observed in pediatrics. Serum transaminase levels and bilirubin should be measured at the start of therapy and monitored at least weekly for the first month of therapy; monitoring frequency can be reduced to monthly during continued use if no clinically significant changes are observed. If liver function tests increase significantly from baseline, voriconazole should be discontinued unless, after assessing the benefit/risk to the patient, continued use is justified.

Voriconazole is primarily metabolized by the liver and has been shown to accumulate significantly in patients with impaired hepatic function. The manufacturer recommends that the maintenance dose be halved in patients with mild to moderate hepatic impairment/cirrhosis. No dosing recommendations are available for patients with severe hepatic impairment/cirrhosis or for patients with chronic hepatitis B or C. Voriconazole should only be used in patients with severe hepatic impairment if benefit outweighs the potential risk. Patients with hepatic impairment must be carefully monitored for drug toxicity.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

The pharmacokinetics of voriconazole are not significantly altered by impaired renal function. However, accumulation of the IV vehicle, sulfobutyl ether beta-cyclodextrin sodium (SBECD), occurs in patients with moderate or severe renal dysfunction (CrCl less than 50 mL/min). The mean systemic exposure (AUC) and Cmax of SBECD were increased 4-fold and almost 50%, respectively, in moderately impaired patients compared to controls with normal renal function. The manufacturer recommends that oral voriconazole be used in patients with moderate to severe renal dysfunction, unless after assessing benefit/risk to the patient, use of IV voriconazole is justified; serum creatinine levels should be monitored closely in these patients, and if increases occur, switching to oral voriconazole should be considered. No dosage adjustment is necessary when using oral voriconazole. Monitoring of renal function (including laboratory evaluation of serum creatinine) is recommended.

Patients with risk factors for acute pancreatitis (e.g., recent chemotherapy, hematopoietic stem cell transplantation) should be monitored for the development of pancreatitis during voriconazole therapy.