Vfend Voriconazole Tablets

1. Indications and Usage
Invasive Aspergillosis (IA):
Indicated for the treatment of invasive aspergillosis in adults and pediatric patients (2 years of age and older).
Candidemia in Non-neutropenic Patients:
Indicated for the treatment of candidemia in the absence of tissue dissemination in non-neutropenic patients.
Serious Fungal Infections:
Indicated for the treatment of serious fungal infections caused by Scedosporium apiospermum(asexual form of Pseudallescheria boydii) and Fusarium spp. in patients intolerant of, or refractory to, other therapy.
2. Dosage and Administration
Recommended Dosage:
Adults (Oral):
Loading Dose (First 24 hours): 400 mg every 12 hours.
Maintenance Dose: 200 mg every 12 hours.
Dose Escalation: If treatment response is poor, maintenance dose may be increased to 300 mg every 12 hours.
Pediatric Patients (Oral): Dosing is weight-based (typically 9 mg/kg every 12 hours, not to exceed adult doses).
Administration Instructions:
Take at least 1 hour before or 1 hour after a meal.
Do not administer with food as high-fat meals significantly reduce absorption.
Monitoring:
Therapeutic Drug Monitoring (TDM) is recommended to ensure efficacy and minimize toxicity, as pharmacokinetics are non-linear.
3. Mechanism of Action
Azole Antifungal:
Voriconazole inhibits the fungal cytochrome P450-mediated enzyme 14α-sterol demethylase.
Physiological Effect:
This inhibition prevents the conversion of 14α-methylergosta-9(11)-en-3β-ol to eburicol, thereby inhibiting the biosynthesis of ergosterol, an essential component of the fungal cell wall.
4. Safety and Warnings
Hepatotoxicity:
Voriconazole may cause liver injury (elevated liver enzymes, hepatitis, jaundice). Monitor hepatic function (AST/ALT) regularly.
Visual Disturbances:
Visual changes (blurred vision, photophobia, altered color vision) are common and usually reversible. Advise patients not to drive at night or in dim light while on therapy.
QT Prolongation:
Voriconazole may prolong the QTc interval. Use with caution in patients with cardiac conduction abnormalities or those taking other QT-prolonging drugs.
Skin Cancer:
Long-term use is associated with an increased risk of squamous cell carcinoma of the skin. Patients should avoid direct sunlight and use protective measures.
5. Adverse Reactions
Most Common:
Visual disturbances, fever, rash, nausea, vomiting, diarrhea, headache, sepsis, peripheral edema, abdominal pain, and respiratory disorders.
6. Drug Interactions
Contraindicated Drugs:
Increases levels of: Terfenadine, cisapride, pimozide, quinidine, ergot alkaloids, sirolimus.
Decreases levels of: Rifampin, carbamazepine, long-acting barbiturates, efavirenz, ritonavir (high dose), lopinavir/ritonavir, rifabutin.
CYP450 Interactions:
Voriconazole is a substrate, inhibitor, and inducer of CYP3A4, CYP2C9, and CYP2C19.
7. Pharmaceutical Information
Storage:
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Protect from moisture.