histoplasmosis, blastomycosis, sporotrichosis, and ringworm and neither prevents nor treats aspergillosis or mucormycosis.

untoward effects

Nausea and vomiting may occur at doses >200 mg/day; patients receiving 800 mg daily may require parenteral antiemetics. Regardless of dose, side effects in patients receiving >7 days of drug include nausea, headache, skin rash, vomiting, abdominal pain, and diarrhea (all at 1-4%). Reversible alopecia may occur with prolonged therapy at 400 mg daily. Rare deaths due to hepatic failure or Stevens-Johnson syndrome have occurred. Fluconazole is associated with skeletal and cardiac deformities in infants born to women taking high doses during pregnancy and should be avoided during pregnancy (category C).

Fluconazole (DIFLUCAN, others) is marketed as tablets for oral administration, powder for oral suspension, and intravenous solutions containing 2 mg/mL. Dosage is 50-800 mg once daily for oral or intravenous administration. Children are treated with 3-6 mg/kg once daily.


Voriconazole (vfend; UK-109,495) is a triazole that is similar to fluconazole but has increased activity and an expanded spectrum.

absorption, distribution, and excretion

Oral bioavailability is nearly complete, and gastric acid is not necessary for absorption. The volume of distribution is high (4.6 L/kg), with extensive tissue distribution; metabolism is by hepatic CYPs, especially 2C19. Less than 2% of native drug but most of the inactive metabolites are secreted in the urine. The oral dose is not adjusted for azotemia or hemodialysis.

Plasma elimination t/2 is 6 hours. Voriconazole exhibits nonlinear kinetics, and higher doses disproportionately increase drug exposure. Genetic polymorphisms in CYP2C19 can cause up to a fourfold difference in drug exposure; ~20% of Asians are poor metabolizers compared to 2% of Caucasians and African Americans. Drug exposure is increased considerably in the elderly and in patients with mild or moderate hepatic insufficiency. Patients with hepatic cirrhosis should receive the same loading dose of voriconazole but half the maintenance dose.

The intravenous formulation of voriconazole contains sulfobutyl ether p-cyclodextrin (SBECD), which is excreted by the kidney. Accumulation of SBECD occurs with a creatinine clearance <50 mL/min; in that setting, oral voriconazole is preferred.

drug interactions

In decreasing rank order, voriconazole is metabolized by, and inhibits, CYP2C19, CYP2C9, and CYP3A4, as does its major metabolite, voriconazole N-oxide. Inhibitors or inducers of these enzymes may increase or decrease voriconazole plasma concentrations, respectively, while voriconazole may increase the plasma concentrations of other drugs metabolized by these enzymes.

Coadministration with rifampin, rifabutin, or ritonavir is contraindicated because of accelerated voriconazole metabolism. Efavirenz and perhaps other nonnucleoside reverse transcrip-tase inhibitors (NNRTIs) significantly increase voriconazole metabolism and slow the metabolism of the NNRTI. When given with phenytoin, the voriconazole dose should be doubled. Drugs that significantly accumulate in patients receiving voriconazole include cyclosporine, dosage

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook

Post a comment