Voriconazole
Mechanism :
Interferes with fungal cytochrome P450 activity (selectively inhibits 14-alpha-lanosterol demethylation), decreasing ergosterol synthesis and inhibiting fungal cell membrane formation.
Indication :
- Invasive aspergillosis
- Esophageal candidiasis
- Candidemia
- Serious fungal infections caused by Scedosporium apiospermum and Fusarium spp.
Contraindications :
Hypersensitivity to voriconazole or any component of the formulation; coadministration with astemizole, barbiturates (long acting), carbamazepine, cisapride, conivaptan, efavirenz (≥400 mg daily), ergot derivatives (ergotamine and dihydroergotamine), pimozide, quinidine, rifampin, rifabutin, ritonavir (≥800 mg daily; also avoid low dose [e.g., 200 mg daily] dosing if possible).
Dosing :
2 years of age and older:
9 mg/kg/dose IV/PO every 12 hours; not to exceed 350 mg/dose.
≥12 years:
6 mg/kg IV 12 hourly for first 24 hours, then 4 mg/kg IV 12 hourly or 200 mg PO 12 hourly for 10 days.
Adverse Effect :
Hallucination, visual disturbance, increased serum creatinine, tachycardia, skin rash, chills, headache, increased serum alkaline phosphatase, increased serum AST & ALT, cholestatic jaundice, fever.
Squamous cell carcinoma has been reported in patients who experience photosensitivity reactions. Pancreatitis in children
Interaction :
Astemizole: Voriconazole increases levels of astemizole by decreasing metabolism. Contraindicated. Risk of QT interval prolongation.
Carbamazepine: Decreases levels of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
Cisapride: Voriconazole increases levels of cisapride by decreasing metabolism. Contraindicated. Risk of QT interval prolongation.
Dihydroergotamine: Voriconazole will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
Efavirenz: Voriconazole will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindication applies to efavirenz doses of 400 mg/day or higher. This dose of efavirenz induces CYP3A4 resulting in decreased voriconazole levels. When voriconazole is coadministered with efavirenz, voriconazole oral maintenance dose should be increased to 400 mg q12hr and efavirenz should be decreased to 300 mg q24hr.
Phenobarbital: Decreases levels of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
Rifampin: Decreases levels of voriconazole by increasing metabolism. Contraindicated.
Ritonavir: Voriconazole will increase the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
Ritonavir: Decreases levels of voriconazole by increasing metabolism. Contraindicated. Ritonavir 400 mg BID decreases voriconazole levels; lower ritonavir doses have unknown effect.
Terfenadine: Voriconazole increases levels of terfenadine by decreasing metabolism. Contraindicated. Risk of QT interval prolongation.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function. |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Probably dialysed. Dose as in normal renal function |
| HD | Dialysed. Dose as in normal renal function |
| HDF/High flux | Dialysed. Dose as in normal renal function |
| CAV/VVHD | Probably dialysed. Dose as in normal renal function |
Hepatic Dose :
Mild to moderate hepatic impairment: Loading dose can be kept the same, but maintenance dose should be reduced to half.
Severe impairment: Avoid use. Use carefully and only if benefits are greater than the risk.