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Introduction |
Voriconazole (Vfend) (Pfizer) was approved in 2002 for the treatment of invasive aspergillosis, Fusarium and Scedosporium infections as well as the treatment of resistant candidiasis. It is referred to as a second generation triazole. Structurally it has some resemblance to fluconazole its activity and handling by the body is completely different. |
Dose & Delivery |
Both oral and intravenous preparations of voriconazole are available. For intravenous usage a loading dose of 6mg/Kg twice at 12 hour intervals is recommended for life threatening infections. Lower treatment doses should be given to those weighing less than 40Kg. Bioavailability is nearly 100% so oral dosing can be relied upon. The dose in children should be 4mg/Kg twice daily, either intravenously or orally. Very small children may require proportionately larger doses. If drug-monitoring facilities are available the dose can be altered on the basis of blood levels. Dose increases result in disproportionate increase in drug exposure because the pharmacokinetics of the drugs are not linear. |
Fungi the drug is active against. |
Voriconazole has an extremely broad spectum. It is active against the vast majority of Candida species, Cryptococcus neoformans, all Aspergillus species, Scedosporium agiospermum, some isolates of Fusarium and a multitude of rather rare pathogens. It is not active against Mucorales species such as Mucor spp, Rhizopus spp, Rhizomucor spp, Absidia spp and others. |
Typical regimens |
Invasive aspergillosis – 6mg/Kg twice (loading) followed by 3-4 mg/Kg twice daily followed by 200mg twice daily orally. |
Metabolism and excretion |
Voriconazole is metabolised by the liver. The most important enzymes involved
in this metabolism are CYP2C19, CYP 3A4 and CYP 2C9. Genetic variation between
different individuals, particularly with CYP 2C19 effects the rate at which
the drug is metabolised. Slow metabolisers are found in about 3% of caucasians
and in approximately 20% of patients from Japan and other parts of Asia. These
patients may accumulate drug and sometimes very high concentrations are found
in the blood.
Young children appear to metabolise the drug very fast. It may be necessary
to increase the dose in young children |
Drug/Drug interactions |
As with most azoles there are a substantial number of drug drug interactions with voriconazole. Drugs, which reduce the effective exposure of voriconazole, include rifampicin, refabutin (less marked), phenytoin and carbamazapine. Interactions with other drugs that result in increased exposure to those drugs including the antihistamines (terfenadine and astemizole), prednisolone, sirolimus, cyclosporin (half dose), tacrolimus (reduce dose to one third), ergotamine, warfarin, sulphonylureas, statins, midazolam and other benzodiazepines, vincristine and some HIV drugs. |
Side effects |
Perhaps the most common side effect associated with voriconazole is visual
side effects. Patients describe wavy lines, mild blurred vision or photophobia
in the first few days after taking voriconazole, which typically lasts a
few minutes. Extensive investigations have not unearthed the precise mechanism
but the side effect wears off over time and has no potential for long term
damage to the eye.
Some patients develop abnormal liver function tests with voriconazole and if these are remarkably elevated then the drug should be stopped. Occasional serious side effects here occurred in patients with very high
concentrations of voriconazole. The long term usage of voriconazole may
lead to reddening of the face and dryness of the lips. If this is serious
it can be improved by the use of sunscreen. |
Other information |
Detailed information is available in the treatment section of the Aspergillus website. |