(±)-Voriconazole

349.310

349.31

JFU09I87TR

759888

DTXSID5046485

C1707

J02AC03|J - Antiinfectives for systemic use

76.72000

0.93

1.4±0.1 g/cm3

127-130°C

508.6±60.0 °C at 760 mmHg

261.4±32.9 °C

1.617

Low|9.78e-02 g/L

|Danger|H301 (99.43%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P264, P270, P273, P281, P301+P310, P308+P313, P314, P321, P330, P391, P405, and P501|Aggregated GHS information provided by 176 companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|H400 (100%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]|P273, P391, and P501|Aggregated GHS information provided by 89 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The minimum lethal oral dose in mice and rats was 300 mg/kg (equivalent to 4 and 7 times the recommended maintenance dose (RMD), based on body surface area). At this dose, clinical signs observed in both mice and rats included salivation, mydriasis, titubation (loss of balance while moving), depressed behavior, prostration, partially closed eyes, and dyspnea. Other signs in mice were convulsions, corneal opacification and swollen abdomen.

Transient elevations in serum aminotransferase levels occur in 11% to 19% of patients on voriconazole. These elevations are usually asymptomatic and self-limited, but approximately 1% of patients require discontinuation of voriconazole because of ALT elevations. Clinically apparent hepatotoxicity is uncommon, but may be more frequent than with fluconazole and itraconazole. The injury arises within the first month of therapy and the pattern of serum enzyme elevations has been variable from cholestatic to hepatocellular. Several cases of acute liver failure attributed to voriconazole have been reported. Immunoallergic features and autoantibodies are uncommon. Recovery upon stopping therapy generally takes 6 to 10 weeks but, in some cases, the time to complete resolution may be prolonged.

58%

For the treatment of esophageal candidiasis, invasive pulmonary aspergillosis, and serious fungal infections caused by Scedosporium apiospermum and Fusarium spp.|FDA Label|Voriconazole is a broad spectrum, triazole antifungal agent and is indicated in adults and children aged 2 years and above as follows:treatment of invasive aspergillosis;treatment of candidaemia in non-neutropenic patients;treatment of fluconazole-resistant serious invasive Candida infections (including C. krusei);treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp.Voriconazole should be administered primarily to patients with progressive, possibly life-threatening infections.Prophylaxis of invasive fungal infections in high risk allogeneic hematopoietic stem cell transplant (HSCT)recipients.|Voriconazole, is a broad spectrum, triazole antifungal agent and is indicated in adults and children aged 2 years and above as follows:treatment of invasive aspergillosis;treatment of in candidaemianon-neutropenic patients;treatment of fluconazole-resistant serious invasive Candida infections (including C. krusei);Treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp.Vfend should be administered primarily to patients with progressive, possibly life-threatening infections.Prophylaxis of invasive fungal infections in high risk allogeneic hematopoietic stem cell transplant (HSCT) recipients.|Voriconazole is a broad-spectrum, triazole antifungal agent and is indicated in adults and children aged two years and above as follows:treatment of invasive aspergillosis;treatment of candidaemia in non-neutropenic patients;treatment of fluconazole-resistant serious invasive Candida infections (including C. krusei);Treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp.Voriconazole Accord should be administered primarily to patients with progressive, possibly life-threatening infections.|Treatment of candidaemia in non-neutropenic patients, Treatment of fluconazole-resistant serious invasive Candida infections (including C. krusei), Treatment of invasive aspergillosis, Treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp.

Voriconazole is a triazole antifungal agent used primarily in the treatment or prevention of aspergillosis and candidal infections. Voriconazole therapy is associated with transient, asymptomatic serum aminotransferase elevations and is a known cause of clinically apparent acute drug induced liver injury.

Antifungal Agents

Voriconazole is a triazole antifungal agent indicated for use in the treatment of fungal infections including invasive aspergillosis, esophageal candidiasis, and serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani. Fungal plasma membranes are similar to mammalian plasma membranes, differing in having the nonpolar sterol ergosterol, rather than cholesterol, as the principal sterol. Membrane sterols such as ergosterol provide structure, modulation of membrane fluidity, and possibly control of some physiologic events. Voriconazole effects the formation of the fungal plasma membrane by indirectly inhibiting the biosynthesis of ergosterol. This results in plasma membrane permeability changes and inhibition of growth.

Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism. (See all compounds classified as 14-alpha Demethylase Inhibitors.)|Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP3A. (See all compounds classified as Cytochrome P-450 CYP3A Inhibitors.)|Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. (See all compounds classified as Antifungal Agents.)

The oral bioavailability is estimated to be 96% (CV 13%).|Voriconazole is eliminated via hepatic metabolism with less than 2% of the dose excreted unchanged in the urine.|4.6 L/kg

Hepatic. The major metabolite of voriconazole is the N-oxide, which accounts for 72% of the circulating radiolabelled metabolites in plasma. Since this metabolite has minimal antifungal activity, it does not contribute to the overall efficacy of voriconazole.|Voriconazole has known human metabolites that include Hydroxymethyl Voriconazole and Voriconazole N-Oxide.

Voriconazole binds and inhibits ergosterol synthesis by inhibiting CYP450-dependent 14-alpha sterol demethylase. The inhibition of 14-alpha sterol demethylase results in a depletion of ergosterol in fungal cell membrane.

UK 109,496

Human drugs -> Voriconazole Hikma (previously Voriconazole Hospira) -> EMA Drug Category|Antimycotics for systemic use -> Human pharmacotherapeutic group|Human drugs -> Vfend -> EMA Drug Category|Human drugs -> Voriconazole Accord -> EMA Drug Category|Antimycotics for systemic use, Triazole derivatives -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Fungicides