Voriconazole, a second-generation triazole antifungal, inhibits fungal cytochrome P450-dependent 14α-lanosterol demethylase, blocking ergosterol synthesis. Ergosterol depletion disrupts fungal cell membrane integrity, leading to cell lysis. Voriconazole is fungicidal against Aspergillus and fungistatic against Candida. It is effective against:

• Aspergillus fumigatus and other Aspergillus species.
• Candida species (including fluconazole-resistant strains like C. krusei and C. glabrata).
• Cryptococcus neoformans.
• Fusarium and Scedosporium species.

Voriconazole is indicated for:

1. Invasive Aspergillosis: First-line therapy (BNF).
2. Candidemia: For non-neutropenic patients.
3. Esophageal Candidiasis: When resistant to fluconazole.
4. Rare Fungal Infections:
   • Scedosporium apiospermum and Fusarium infections.
5. Prophylaxis: In high-risk immunocompromised patients (e.g., stem cell transplant recipients).

Adults:

• Loading Dose: 6 mg/kg IV every 12 hours for 2 doses.
• Maintenance Dose: 4 mg/kg IV every 12 hours or 200 mg orally every 12 hours.
• Oral Dosing: Switch to oral therapy once clinically stable.

Children (2–12 years):

• Loading Dose: 9 mg/kg IV every 12 hours for 2 doses.
• Maintenance Dose: 8 mg/kg IV every 12 hours or 200 mg orally every 12 hours.

Special Populations:

• Hepatic Impairment: Reduce maintenance dose by 50% in mild to moderate impairment (Child-Pugh A/B). Avoid in severe impairment (Child-Pugh C).
• Renal Impairment: No adjustment for oral use; avoid IV formulation (due to cyclodextrin excipient).

• Photosensitivity: Severe sunburn with UV exposure.
• Hallucinations/Confusion: Neuropsychiatric effects (dose-dependent).
• Bone Toxicity: Periostitis with long-term use.

Precautions

1. Hepatic/Renal Impairment: Monitor LFTs and adjust dose. Avoid IV in severe renal impairment.
2. Pregnancy: Category D (teratogenic in animal studies; avoid unless benefits outweigh risks).
3. Lactation: Excreted in breast milk; avoid breastfeeding.
4. Cardiac Conditions: Avoid in patients with prolonged QT interval.
5. Photosensitivity: Advise patients to avoid direct sunlight and use sunscreen.

Drug Interactions

Voriconazole is a CYP3A4 inhibitor and substrate, leading to significant interactions:

• CYP3A4 Substrates:
  • Sirolimus: Contraindicated (increased toxicity).
  • Cyclosporine/Tacrolimus: Reduce dose and monitor levels.
  • Statins: Increased risk of myopathy (e.g., simvastatin).
• CYP3A4 Inducers:
  • Rifampicin/Phenytoin: Reduce voriconazole levels (avoid combination).
• QT-Prolonging Drugs:
  • Quinolones/Macrolides: Increased risk of arrhythmias.
• Warfarin: Increased INR (monitor closely).

1. Hepatic Impairment: Avoid in severe liver disease.
2. Pregnancy: Category C (teratogenic in animal studies; avoid unless benefits outweigh risks).
3. Lactation: Excreted in breast milk; avoid breastfeeding.
4. Photosensitivity: Advise patients to avoid direct sunlight and use sunscreen.
5. Alcohol: Disulfiram-like reaction (flushing, tachycardia).

•  

  Voriconazole is a CYP3A4 inhibitor and substrate, leading to significant interactions:

  • CYP3A4 Substrates:
    • Sirolimus: Contraindicated (increased toxicity).
    • Cyclosporine/Tacrolimus: Reduce dose and monitor levels.
    • Statins: Increased risk of myopathy (e.g., simvastatin).
  • CYP3A4 Inducers:
    • Rifampicin/Phenytoin: Reduce voriconazole levels (avoid combination).
  • QT-Prolonging Drugs:
    • Quinolones/Macrolides: Increased risk of arrhythmias.
  • Warfarin: Increased INR (monitor closely).

Generic & Brand Names

• Generic: Voriconazole.
• Brand Names: Vfend (oral/IV).