Generic Name

Voriconazole

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Classification

FDA Approved Indications

• Invasive aspergillosis
• Serious infections caused by Scedosporium apiospermum and Fusarium spp.
• Vaginal candidiasis (not first-line)

Mechanism of Action

Voriconazole inhibits fungal cytochrome P450-dependent 14α-lanosterol demethylation, a key step in ergosterol synthesis, leading to increased membrane permeability and fungal cell death.

Dosage and Administration

Adult: Loading dose of 6 mg/kg IV every 12 hours for two doses, followed by 4 mg/kg IV every 12 hours; oral dose is 200 mg twice daily.

Pediatric: Dose varies based on weight and age; typically, 7 mg/kg IV every 12 hours for two doses, then 3 mg/kg IV every 12 hours; oral dosing of 200 mg twice daily.

Geriatric: No specific adjustment, but caution advised due to increased risk of adverse effects.

Renal Impairment: No adjustment for mild; use caution for moderate to severe—dose adjustments may be necessary.

Hepatic Impairment: Initial dose reduction recommended for severe hepatic impairment.

Pharmacokinetics

Absorption: Good oral bioavailability (~96%)

Distribution: Wide tissue distribution, high CSF penetration

Metabolism: Primarily via hepatic CYP2C19, CYP2C9, CYP3A4

Excretion: Mostly as metabolites via urine and feces

Half Life: First half-life approximately 6 hours; steady-state usually reached in 2 days with chronic dosing.

Contraindications

• History of hypersensitivity to voriconazole or other azoles

Precautions

• Monitor for hepatotoxicity, visual changes, skin reactions, and drug interactions.
• Use with caution in hepatic impairment, monitor liver function tests regularly.
• Pregnancy Category D—risk-benefit analysis required.
• Lactation: unknown safety; avoid breastfeeding during treatment.

Adverse Reactions - Common

• Visual disturbances (blurriness, color vision change) (frequent)
• Liver enzyme elevations (frequent)
• Skin rash (frequent)
• Nausea and vomiting (common)

Adverse Reactions - Serious

• Stevens-Johnson syndrome (rare)
• Hepatotoxicity leading to liver failure (rare)
• QT prolongation leading to arrhythmias (rare)
• Hallucinations, confusion, or neurotoxicity (especially at high doses) (rare)

Drug-Drug Interactions

• CYP3A4 inhibitors or inducers (e.g., rifampin, carbamazepine, erythromycin)
• Other drugs prolonging QT interval (e.g., quinidine, amiodarone)

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Report visual changes, skin rashes, or unusual symptoms immediately.
• Take medication with food or without food, as directed.
• Avoid driving or operating machinery if experiencing visual disturbances.
• Inform healthcare provider of all medications being taken to avoid interactions.

Special Considerations

Black Box Warnings:

• Risk of hepatotoxicity, QT prolongation, and allergic reactions

Genetic Factors: CYP2C19 polymorphisms can affect metabolism and serum levels (poor vs. extensive metabolizers).

Lab Test Interference: Possible laboratory interference with bilirubin and liver function tests.

Overdose Management

Signs/Symptoms: Nausea, vomiting, visual disturbances, neurological symptoms, elevated liver enzymes.

Treatment: Supportive care, activated charcoal if ingestion recent, and monitoring; hemodialysis unlikely to remove drug effectively.

Storage and Handling

Storage: Store at 20-25°C (68-77°F); protect from light.

Stability: Stable until expiration date when stored properly.