Voriconazole

Voriconazole is a triazole antifungal medication used to treat serious fungal infections. It is used to treat invasive fungal infections that are generally seen in patients who are immunocompromised. These include invasive candidiasis, invasive aspergillosis, and emerging fungal infections. The increased affinity of voriconazole for 14-alpha sterol demethylase makes it useful against some fluconazole-resistant organisms.

Voriconazole is a triazole compound used to treat fungal infections.

For the treatment of esophageal candidiasis, cadidemia, invasive pulmonary aspergillosis, and serious fungal infections caused by Scedosporium apiospermum and Fusarium spp.

• Aspergillosis of the Central Nervous System
• Aspergillosis of the Liver
• Candidemia
• Candidiasis
• Coccidioidomycosis
• Endocarditis caused by Aspergillus
• Esophageal Candidiasis
• Fungal meningitis caused by Exserohilum Infection
• Fusarium infection
• Histoplasmosis
• Infections
• Fungal
• Invasive Aspergillosis
• Osteomyelitis caused by Aspergillus
• Penicillium marneffei infection
• Peritonitis caused by Aspergillus
• Scedosporium Infection
• Sinusitis aspergillus
• Aspergillus endophthalmitis
• Disseminated Candidiasis
• Refractory Fungal Infections
• Refractory Oral Candidiasis

Voriconazole is a fungistatic triazole antifungal used to treat infections by inhibiting fungal growth. It is known to cause hepatotoxic and photosensitivity reactions in some patients.

Voriconazole is used to treat fungal infections caused by a variety of organisms but including Aspergillus spp. and Candida spp. Voriconazole is a triazole antifungal exhibiting fungistatic activity against fungal pathogens. Like other triazoles, voriconazole binds to 14-alpha sterol demethylase, also known as CYP51, and inhibits the demethylation of lanosterol as part of the ergosterol synthesis pathway in yeast and other fungi. The lack of sufficient ergosterol disrupts fungal cell membrane function and limits fungal cell growth. With fungal growth limited, the host's immune system is able to clear the invading organism.

The oral bioavailability is estimated to be 96% in healthy adults. Population pharmacokinetic studies report a reduced bioavailability pediatric patients with a mean of 61.8% (range 44.6–64.5%) thought to be due to differences in first-pass metabolism or due to differences in diet . Of note, transplant patients also have reduced bioavailability but this is known to increase with time after transplantation and may be due in part to gastrointestinal upset from surgery and some transplant medications. Tmax is 1-2 hours with oral administration. When administered with a high-fat meal Cmax decreases by 34% and AUC by 24%. pH does not have an effect on absorption of voriconazole. Differences in Cmax and AUC have been observed between healthy adult males and females with Cmax increasing by 83% and AUC by 113% although this has not been observed to significantly impact medication safety profiles.

The estimated volume of distribution of voriconazole is 4.6 L/kg . Population pharmacokinetic studies estimate the median volume of distribution to be 77.6 L with the central compartment estimated at 1.07 L/kg Voriconazole is known to achieve therapeutic concentrations in many tissues including the brain, lungs, liver, spleen, kidneys, and heart.

Voriconazole is 58% bound to plasma proteins .

Voriconazole is eliminated via hepatic metabolism with less than 2% of the dose excreted unchanged in the urine.

Voriconazole follows non-linear kinetics and has a terminal half-life of elimination which is dose-dependent.

The clearance of voriconazole is estimated to be a mean of 5.25-7 L/h in healthy adults for the linear portion of the drug's kinetics.

Symptoms of overdose include photophobia and possible QTc prolongation. In case of overdose, supportive care and ECG monitoring are recommended. Activated charcoal may aid in the removal of unabsorbed drug. Voriconazole is cleared by hemodialysis at a rate of 121 mL/min which may be helpful in removing absorbed drug. Carcinogenicity studies found hepatocellular adenomas in female rats at doses of 50 mg/kg and hepatocellular carcinomas found in male rats at doses of 6 and 50 mg/kg. These doses are equivalent to 0.2 and 1.6 times the recommended maintenance dose (RMD). Studies in mice detected hepatocellular carcinomas in males at doses of 100 mg/kg or 1.4 times the RMD. Hepatocellular adenomas were detected in both male and female mice.

• Take separate from meals. Take voriconazole at least one hour before or after eating for optimal absorption.

• At or over 40 kg body weight: Loading dose regimen is 400 mg or 10 ml every 12 hours (for the first 24 hours) and maintenance dose (after first 24 hours) is 200 mg or 5 ml twice daily.
• Below 40 Kg body weight: Loading dose regimen is 200 mg or 5 ml every 12 hours (for the first 24 hours) and maintenance dose (after first 24 hours) is 100 mg or 2.5 ml twice daily. Or, as directed by the registered physician.

• Loading dose: 6 mg/kg 12 hourly for the first 24 hours.
• Maintenance Dose: 4 mg/kg 12 hourly.

• Loading dose: 6 mg/kg 12 hourly for the first 24 hours.
• Maintenance Dose: 3-4 mg/kg 12 hourly.

• Loading dose: 6 mg/kg 12 hourly for the first 24 hours.
• Maintenance Dose: 4 mg/kg 12 hourly.