Dosing
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 pharmacokinetics, 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 the 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).
Postmarketing 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 an increase in LFTs.
It is a fluoride salt, and long term 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 your 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
Curious Cases
Relevant links to my Medscape blog
Last update 11/30/19