Voriconazole belongs to a group of drugs called triazole antifungal agents. These medicines are used to treat a wide variety of fungal infections. It works by killing or stopping the growth of the fungi that cause infections by blocking fungal cell wall growth, resulting in the death of the fungus. It can also be used to prevent fungal infections in people whose immune system is not working properly.
Compared with older azole drugs, ketoconazole, fluconazole, and itraconazole, voriconazole has a broader spectrum of antifungal activity, including Aspergillus species, endemic fungi, azole-resistant candida species, and a variety of other pathogenic opportunistic fungi such as Fusarium species, Pseudallescheria boydii, Scedosporium species, and dematiaceous fungi.

Indications & Usage:
It is used for the treatment of patients (adults and children over the age of 12) with:
Invasive aspergillosis (a type of fungal infections due to Aspergillus species), including treatment of invasive aspergillosis in patients intolerant of, or whose disease is refractory to other antifungals.
Candidaemia (another type of fungal infection due to Candida species) in non- neutropic patients (patients without abnormal low blood white cells count).
● Serious invasive Candida species infections when the fungus is resistant to fluconazole (another antifungal medicine).
● Serious fungal infections caused by Scedosporium species or Fusarium species (two different species of fungi).
● Voriconazole is intended for patients with worsening, possibly life-threatening, fungal infections.
● For HIV-infected adults and adolescents with invasive aspergillosis, voriconazole is recommended as the drug of choice.

Mechanism of Action:
The mechanism of action of voriconazole, similar to that of all azole agents, is inhibition of cytochrome P450 (CYP 450) – dependent 14a-lanosterol demethylation, which is a vital step in cell membrane ergosterol synthesis by fungi. For yeasts, voriconazole appears to be fungistatic, as are other azoles. However, for some filamentous organisms, voriconazole and other second-generation azoles are fungicidal. This effect may relate to the stronger avidity of the new azoles for the lanosterol 14a-demethylase found in molds, compared with that found in yeasts, which may allow more-complete interruption of ergosterol synthesis and lead to cell death.

Drug Interactions:
● Decreases voriconazole levels: Carbamazepine, Long-acting Barbiturates, Rifampin.
● Levels increased by voriconazole: Astemizole, Cisapride, Cyclosporine, Ergot alkaloids, Omeprazole, Quinidine, Sirolimus, Tacrolimus, Terfinadine, Warfarin.
● Decreases voriconazole levels and increases other drug levels: Rifabutin, Phenytoin.
● Levels likely increased by voriconazole: Sulfonylureas, Statins, Vinca –alkaloids, Calcium channel blockers, Benzodiazepines.

Pharmacokinetics:
Absorption: When administered either 1 h before or 1h after a meal, the bioavailability of the oral formulation is ˃ 90%. Gastric acid is not needed for absorption; fatty foods decrease bioavailability to ~ 80%. In adults, after oral administration of 200 mg twice daily, steady-state plasma concentrations generally range from 2 to 3 mg/mL. Patients who weigh ˃ 40 kg should receive 200 mg every 12 h, and those who weigh ˂ 40 kg should receive 100 mg every 12 h. Steady-state concentrations are achieved within 24 h if a loading dose twice the amount of the daily dosage is given on day 1. In adults, voriconazole exhibits nonlinear pharmacokinetics, which is thought to be related to saturation of metabolism. There is substantial intersubject variability in the serum concentrations achieved. In children, elimination is linear, and higher dosages are required to attain the serum concentrations noted in adults.
Distribution: Voriconazole is 58% protein bound and has a large volume of distribution. In animals and humans, concentrations in the CSF are ~ 50% of plasma concentrations; concentrations in brain tissue are higher than those in the CSF.
Metabolism: Metabolism of voriconazole occurs in the liver via the CYP450 enzyme family, including the CYP2C9, CYP3A4, and CYP2C19 isoenzymes. The metabolites do not have antifungal activity. The activity of the CYP2C19 pathway, which is the major metabolic pathway for voriconazole, is highly dependent on genetic characteristics.
Excretion: Less than 5% of the drug is excreted unchanged in the urine.

Side Effects:
More Common: Difficulty seeing at night, increased sensitivity of the eyes to sunlight, rash, vision changes.
Less Common: Abdominal or stomach pain, bloating or swelling of the face, arms, hands, lower legs, or feet, clay-colored stools, confusion, dark urine, decreased urine, dizziness, dry mouth, fever, muscle pain or cramps, nausea, unusual tiredness or weakness.

Contraindications:
● Drugs which are contraindicated: Carbamazepine, Long-acting Barbiturates, Rifampin, Astemizole, Cisapride, Ergot alkaloids, Quinidine, Sirolimus, Terfinadine, Rifabutin.
● Voriconazole is contraindicated in Pregnancy & Lactation.
● In Patients of known hypersensitivity to Voriconazole.

Warning & Precautions:
● Tell your doctor or dentist that you take voriconazole before you receive any medical or dental care, emergency care, or surgery.
● Voriconazole may cause blurred vision or sensitivity to light. These effects may be worse if you take it with alcohol or certain medicines. Use voriconazole with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.
● Avoid driving at night while you are using voriconazole.
● Voriconazole may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to voriconazole. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.
● Serious and sometimes fatal liver problems have happened with voriconazole. Call your doctor right away if you have symptoms of liver problems (eg, dark urine; itching; pale stools; persistent loss of appetite; severe or persistent nausea, vomiting, or stomach pain; yellowing of the skin or eyes).
● A severe skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause serious health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
● Women who may become pregnant should use effective birth control (eg, birth control pills) while using voriconazole. Talk with your doctor if you have questions about effective birth control.
● Lab tests, including eye exams, liver and kidney function, and pancreas function, may be performed while you use voriconazole. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.
● Caution is advised when using voriconazole in CHILDREN; they may be more sensitive to its effects, especially sunburn or skin reactions to light.
● If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Overdose:
If overdose is suspected, contact a poison control center or emergency room immediately.

Storage:
Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.