Infectious Disease Compendium

Voriconazole (VFend®)

Dosing

CrCl Formula

CrCl > 80:

IV: initially, 6 mg/kg every 12 hours by IV infusion for 2 doses, followed by a maintenance dosage of 4 mg/kg every 12 hours by IV infusion, until patient can be switched to oral therapy.

If this dosage cannot be tolerated, the IV maintenance dosage can be decreased to 3 mg/kg every 12 hours.

Oral: 200 mg every 12 hours (patients weighing more than 40 kg) or 100 mg every 12 hours (patients weighing less than 40 kg) administered at least 1 hour before or 1 hour after a meal. Dosage may be increased to 300 mg every 12 hours (patients weighing more than 40 kg) or 150 mg every 12 hours (patients weighing less than 40 kg).

Given variable pharmakokinectics, in serious fungal infections (are there any other kinds) there should be dosage adjustments based on serum levels (PubMed).

CrCl 80-50:

CrCl 50-10: IV voriconazole should be used only when clearly needed because of accumulation of the IV vehicle; oral therapy needs no dose reduction for altered renal function.

CrCl < 10:

Hemodialysis:

Peritoneal dialysis:

Important side effects

Diarrhea, nausea, vomiting, fever, headache, increased lft's, liver failure, peripheral edema, rash, renal failure, Stevens-Johnsons syndrome, visual disturbances (common), auditory and visual hallucinations (PubMed), rarely neuropathy (PubMed).

Post marketing side effects: "ADEs included liver function test abnormalities (23%), visual disturbances (18%), skin rashes (17%), neurologic disturbances (14%), cardiovascular events (10%), hematologic disorders (8%), and renal disturbances (4%). Other less commonly identified ADEs included headache, nausea, vomiting, and diarrhea. Drug-drug interactions were observed in 7 cases. According to the Naranjo criteria, 84% of ADEs were classified as possible, 7% as probable, 5% as highly probable, and 4% as doubtful (PubMed)."

20% will get in increase in LFT's.

It is a fluoride salt, and long tern use can cause fluoride toxicity with painful periostitis and elevated alkaline phosphatase (PubMed). So follow fluoride levels (PubMed).

Skin cancer from photosensitivity (PubMed).

Important drug interactions

Alfuzosin, amprenavir, astemizole, atazanavir, atorvastatin, barbiturates, benzodiazepines, calcium channel blockers, carbamazepine, cerivastatin, cisapride, cyclosporin, delavirdine, efavirenz, eletriptan, ergot derivatives, erlotinib, erythromycin, fosamprenavir, fosphenytoin, imatinib, lovastatin, nelfinavir, nevirapine, omeprazole, phenytoin, pimozide, quinidine, rifabutin, rifampin, rifapentine, ritonavir, saquinavir, simvastatin, sirolimus, sulfonylureas, tacrolimus, terfenadine, vinca alkaloids, warfarin.

These drugs interact with damn near everything else so check with you pharmacist or this reference at CID.

Dexamethasone will also decrease drug levels (Pubmed)

Rants and Screeds

Look at the brand name. VFend. They need a vowel, guess they had a vowel movement (rimshot). Blood levels can be variable, outcomes can be improved by checking levels (PubMed).

If serum levels are low the drug can be boosted with omeprazole (PubMed).

Pearls

Child-Pugh class A and B the standard loading doses of voriconazole may be used, but the maintenance dosage should be decreased by 50%. Voriconazole has not been studied in patients with Child-Pugh class C.

Treatment of choice

Aspergillus, good for most Candida. Neutropenic fever.

Use for

Don't use for

Class

Triazole