DP is a 60-year-old female with a history of hypertension, hyperlipidemia, and stroke who is receiving induction with cytarabine and daunorubicin for acute myeloid leukemia. She has allergies to penicillin (rash) and aspirin (rash). Home medications include Plavix 75 mg PO daily, Lipitor 40 mg PO daily, and lisinopril 20 mg PO daily. Today DP has new-onset shortness of breath, cough and a positive galactomannan test. Her calculated creatine clearance this morning was 60 mL/min. She is to be started on intravenous VFEND for presumed invasive aspergillosis with further workup pending. Which of the following is/are true about VFEND in this patient? Select all that apply.
A. VFEND will inhibit the metabolism of Plavix, potentially increasing the patient’s bleeding risk
B. VFEND will induce the metabolism of Lipitor, potentially decreasing the effectiveness of Lipitor
C. VFEND may cause QTc prolongation
D. VFEND may cause visual disturbances
E. Based on renal function, this patient should be given 50% of the usual VFEND dose
Answers with rationale:
The correct answers are C and D.
Voriconazole (VFEND) is the drug of choice for treatment of invasive aspergillosis, a fungal infection that most often occurs in immunocompromised patients, such as those receiving chemotherapy. It is an important drug to study due to its many drug interactions and adverse effects.
Voriconazole inhibits CYP2C19 and CYP3A4. Clopidogrel (Plavix) is an inactive prodrug that must be activated in the body by CYP2C19 to carry out its antiplatelet effect. When voriconazole inhibits CYP2C19, less clopidogrel is converted to its active form, increasing the risk of arterial thrombotic events. Answer A is incorrect. Active atorvastatin (Lipitor) is metabolized by CYP3A4, so voriconazole increases atorvastatin serum concentrations, increasing the risk of toxicities. Answers B is incorrect.
Like other azole antifungals, voriconazole can cause QTc prolongation and hepatotoxicity. Visual disturbances, including blurriness and color changes, are adverse effects specific to voriconazole. These visual changes cease once voriconazole therapy is stopped. Answers C and D are correct.
Voriconazole is cleared almost entirely by hepatic metabolism, so renal dose adjustment is not required. Answer E is incorrect. However, keep in mind that IV voriconazole contains an inactive ingredient called cyclodextrin, which increases drug solubility but can accumulate in patients with renal impairment. If possible, patients with creatinine clearance <50 mL/min should receive oral voriconazole, which does not contain cyclodextrin.