CLINICAL: Systemic antifungal. General Action Interferes with cytochrome P-450 activity, an enzyme necessary for ergosterol formation. Therapeutic Effect: Directly damages fungal membrane, altering its function. Fungistatic. Pharmocokinetics Well absorbed from GI tract. Widely distributed, including to CSF. Protein binding: 11%. Partially metabolized in liver. Excreted unchanged primarily in urine. Partially removed by hemodialysis. Halflife: 20–30 hrs (increased in renal impairment). Interactions DRUG: High fluconazole dosages increase cyclosporine, sirolimus, tacrolimus concentrations. Isoniazid, rifampin may increase drug metabolism. May increase concentration/effects of oral antidiabetic medication. May decrease metabolism of phenytoin, warfarin. HERBAL: None significant. FOOD: None known. LAB VALUES: May increase serum alkaline phosphatase, bilirubin, ALT, AST. Indications/Routes/Dosage PO and IV therapy equally effective; IV therapy for pt intolerant of drug or unable to take orally. Oral suspension stable for 14 days at room temperature or refrigerated. Usual Dosage PO/IV: ADULTS, ELDERLY: 150 mg once or loading dose: 200–800 mg. Maintenance dose: 200–800 mg once daily. CHILDREN AND NEONATES: Loading dose: 6–12 mg/kg. Maintenance dose: 3–12 mg/kg once daily. Maximum: 600 mg/day. Dosage in Renal Impairment After a loading dose of 400 mg, daily dosage is based on creatinine clearance. Creatinine Clearance Dosage Greater than 50 ml/min 100% 50 ml/min or less 50% Dialysis 50% CCRT 400–800 mg as loading dose CVVH then 200–800 mg/ day CVVHDF 400–800 mg as loading dose, then 400–800 mg/ day Dosage in Hepatic Impairment No dose adjustment.