1 Name of Medicine
Voriconazole.
2 Qualitative and Quantitative Composition
Vzole 50 mg film-coated tablets contain 50 mg of voriconazole.
Vzole 200 mg film-coated tablets contain 200 mg of voriconazole.
Voriconazole, a broad-spectrum, triazole antifungal agent, is available as film-coated tablets for oral administration.
Excipients with known effects. Vzole tablets contain sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Vzole 50 mg film-coated tablets are white, round, biconvex film coated 7 mm tablet with 'V50' debossed on one side and plain on other side.
Vzole 200 mg film-coated tablets are white, caplet shaped film coated 15.6 mm tablet with 'V200' debossed on one side and plain on other side.
4 Clinical Particulars
4.9 Overdose
Clinical data on overdose with this agent is scant.
In clinical trials there were three cases of accidental overdose. All occurred in paediatric patients, who received up to five times the recommended intravenous dose of voriconazole. A single adverse event of photophobia of 10 minutes duration was reported.
There is no known antidote to voriconazole. It is recommended that treatment of overdose is symptomatic and supportive.
Monitor potassium, full blood count and liver function following an overdose.
Consider administration of activated charcoal in the event of a potentially toxic ingestion. Activated charcoal is most effective when administered within one hour of ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected.
Voriconazole is haemodialysed with a clearance of 121 mL/min. The intravenous vehicle, hydroxypropylbetadex, is haemodialysed with a clearance of 37.5 ± 24 mL/min. In an overdose, haemodialysis may assist in the removal of voriconazole and hydroxypropylbetadex from the body.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
Genotoxicity. Voriconazole showed no mutagenic potential in gene-mutation assays in bacterial (Salmonella typhimurium) and mammalian (Chinese hamster ovary) cells. While in vitro exposure of human lymphocytes to voriconazole produced equivocal effects on chromosomes, in vivo treatment of male and female mice at doses up to and including the maximum tolerated dose produced no evidence of chromosome damage as determined by the micronucleus assay.
Carcinogenicity. Carcinogenic potential was studied in mice and rats at oral doses of up to 100 mg/kg/day and 50 mg/kg/day for 24 months, respectively. Hepatocellular adenoma appeared in male and female mice at 100 mg/kg/day and in female rats at 50 mg/kg/day. There was also an increased incidence of hepatocellular carcinoma in mice at 100 mg/kg/day. Although mean plasma drug concentrations indicated there is no safety margin in humans in terms of exposure, adenoma and carcinoma (as well as non-neoplastic changes) are known to occur in rodents after chronic administration of compounds that are hepatic enzyme inducers.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Voriconazole drug substance is a white to off white powder. Its aqueous solubility is very low at 0.7 mg/mL at 25°C.
Chemical structure. Voriconazole is designated chemically as (2R, 3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4- pyrimidinyl)-1-(1H -1,2,4-triazol-1-yl)-2-butanol with an empirical formula of C16H14F3N5O and a molecular weight of 349.3.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSVORICO.gif CAS number. 137234-62-9.
7 Medicine Schedule (Poisons Standard)
S4 (Prescription Medicine).
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/VZOLEST.gif
