VARICONAZOLE DENK 200 200MG FILM COATED TABLET

Indications

• Invasive aspergillosis
• Candidemia
• Esophageal candidiasis
• Serious fungal infections due to Scedosporium species
• Fusarium species infections
• Prophylaxis of fungal infections in high-risk patients

Dosage

Children: Refer to

Adults: Refer to the BNF for specific dosing guidelines based on the type of infection and patient factors.

Mechanism of action

Voriconazole works by inhibiting the fungal cytochrome P450 enzyme 14-alpha-sterol demethylase, which is crucial for the synthesis of ergosterol, a vital component of fungal cell membranes. This inhibition disrupts the integrity of the cell membrane, leading to cell death. Voriconazole also has a potent activity against a variety of fungi, including those resistant to other antifungal classes.

Pharmacodynamics

Voriconazole exhibits time-dependent antifungal activity, with its efficacy related to the time that drug concentrations remain above the minimum inhibitory concentration (MIC) for the target organism. It demonstrates a broad spectrum of activity against various fungi, particularly mold species like Aspergillus and dermatophytes. Resistance can occur, particularly in strains of Candida and Aspergillus, and it is essential to monitor susceptibility patterns.

Pharmacokinetics

Voriconazole is well absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is highly protein-bound (approximately 96%) and has a volume of distribution of about 4-5 L/kg. Voriconazole undergoes extensive hepatic metabolism via cytochrome P450 enzymes, particularly CYP2C19, CYP2C9, and CYP3A4, leading to multiple metabolites. The elimination half-life varies significantly, typically ranging from 6 to 12 hours, and is influenced by genetic polymorphisms in metabolic enzymes and concomitant medications.

Contra-indications

• Hypersensitivity to voriconazole or any component of the formulation
• Concomitant use with certain drugs that are strong CYP450 enzyme inducers

Adverse effects

• Visual disturbances
• Hepatotoxicity
• Skin rash
• Nausea
• Headache
• Fever
• Abdominal pain
• Diarrhea
• Hypokalemia

Interactions

• May interact with drugs metabolized by CYP2C19, CYP2C9, and CYP3A4
• Increased risk of hepatotoxicity when used with other hepatotoxic drugs
• Concurrent use with drugs that prolong QT interval may increase risk of arrhythmias

Precautions

• Monitor liver function tests regularly during treatment
• Use caution in patients with a history of liver disease
• Consider potential visual side effects, particularly in patients with existing visual impairment

Pregnancy

Voriconazole is classified as Category D. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known if voriconazole is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store at 20 to 25 degrees Celsius. Protect from light and moisture.

Formulations

• Oral tablets
• Intravenous solution