Voriconazole Dosing and Interactions

Voriconazole, a prescription medication, is a potent triazole antifungal medicine widely used to treat serious fungal or yeast infections in individuals aged 2 and above. However, its complex pharmacokinetics and numerous drug interactions necessitate careful dosing and monitoring. Voriconazole dosing is available in 200mg powder form for injection, 40/mg/ml oral powder for reconstitution, & oral tablets in 200mg and 50mg. Voriconazole side effects should be immediately reported to your doctor, including but not limited to rash, fever, swollen glands, yellow skin/eyes, headache, irregular heartbeats, etc.

What is Voriconazole?

Voriconazole is a broad-spectrum antifungal agent belonging to the triazole class. It is particularly effective against Aspergillus species, Candida species (including fluconazole-resistant strains), and other filamentous fungi.

Active Ingredients

The active ingredient in voriconazole is voriconazole itself.

Voriconazole Mechanism of Action

Voriconazole inhibits fungal cytochrome P450 (CYP450) 14-α-demethylase, a crucial enzyme in ergosterol biosynthesis. Ergosterol is a vital component of fungal cell membranes. By disrupting its synthesis, voriconazole compromises cell membrane integrity, leading to fungal cell death.

Voriconazole Metabolism

Voriconazole is primarily metabolized by hepatic CYP450 enzymes, specifically CYP2C19, CYP2C9, and CYP3A4. CYP2C19 exhibits significant genetic polymorphism, leading to substantial interindividual variability in voriconazole pharmacokinetics. This polymorphism is a major factor in the observed differences in drug exposure among patients.

According to Pubmed, “Sufficient evidence is available for implementing CYP2C19-guided voriconazole selection and dosing among select patients at risk for invasive fungal infections.” Book an at-home PGx test requiring just a saliva swab.

Voriconazole Dosing and Administration

• 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 (adjusted based on therapeutic drug monitoring).
• Oral vs. Intravenous: Voriconazole has high oral bioavailability (~96%), but food can reduce absorption. IV formulation is preferred in critically ill patients or those unable to tolerate oral medication.
• Renal Considerations: The IV formulation contains cyclodextrin, which may accumulate in renal impairment (CrCl < 50 mL/min). In such cases, switching to oral voriconazole is recommended.
• Therapeutic Drug Monitoring (TDM): Recommended trough levels: 1-5.5 mcg/mL to balance efficacy and toxicity.

Do not mix voriconazole liquid with any other medicine or liquid.

Voriconazole Indications

Voriconazole is indicated for the treatment of:

• Invasive aspergillosis
• Serious Candida infections (including esophageal candidiasis)
• Fusariosis
• Scedosporiosis
• Other serious fungal infections

Voriconazole Interactions

Voriconazole’s metabolism through CYP450 enzymes makes it susceptible to numerous drug interactions.

• CYP450 Inhibitors: Drugs that inhibit CYP450 enzymes (e.g., macrolide antibiotics, protease inhibitors) can increase voriconazole levels, leading to toxicity.
• CYP450 Inducers: Drugs that induce CYP450 enzymes (e.g., rifampin, phenytoin, carbamazepine) can decrease voriconazole levels, reducing its efficacy.
• Drugs Affected by Voriconazole: Voriconazole can increase the levels of immunosuppressants (tacrolimus, cyclosporine), statins, benzodiazepines, and warfarin (raising INR and bleeding risk).
• Contraindicated Drugs: Rifampin, rifabutin, carbamazepine, long-acting barbiturates, St. John’s wort, and sirolimus are contraindicated with voriconazole.

Voriconazole Side Effects

In case of serious reactions seek immediate help. Call 911 or get emergency medical help if you have:

• Allergic reaction: Hives, swelling (face/throat), trouble breathing.
• Severe skin reaction: Fever, sore throat, burning eyes, painful skin, or blistering rash.
• Serious drug reaction: Rash, fever, swollen glands, muscle pain, severe weakness, unusual bruising, or yellow skin/eyes.

If receiving IV voriconazole, tell your doctor if you feel:

• Dizzy, nauseous, light-headed, sweaty.
• Have a headache, chest tightness, back pain, or trouble breathing.

Major Side Effects – Call Your Doctor

• Heart problems: Fast, pounding heartbeat, fluttering in chest, dizziness, shortness of breath.
• Skin issues: Severe sunburn.
• Vision changes: Blurry vision, trouble seeing colors.
• Unusual bleeding: Easy bruising, purple/red spots on skin.
• Slow heart rate: Weak pulse, fainting, slow breathing.
• Adrenal issues:
• High hormones: Weight gain, swelling, acne, mood swings, missed periods.
• Low hormones: Stomach pain, fatigue, muscle/joint pain, craving salt.
• Kidney problems: Little or no urine, swelling in feet or ankles.
• Liver problems: Nausea, vomiting, flu-like symptoms, jaundice (yellow skin/eyes).
• Electrolyte imbalance: Dizziness, numbness, muscle cramps, irregular heartbeat.

Common Side Effects

Cold/flu-like symptoms: Fever, chills, stuffy nose, cough, sore throat.

Bleeding/bruising: Nosebleeds, coughing up blood.

Heart issues: High/low blood pressure, fast heartbeat.

Stomach issues: Nausea, vomiting, diarrhea, constipation, bloating.

Swelling: Hands, feet.

Headaches & dizziness.

Rash & skin reactions.

Vision changes & hallucinations.

Abnormal liver tests.

An at home PGx (pharmacogenomics) test by RPh LABS can give you insights into how you may respond to 250+ medications.

Boxed Warnings & Adverse Effects

• Visual Disturbances: Blurred vision, photophobia, and altered color perception.
• Hepatotoxicity: Elevated liver enzymes and rare cases of acute liver failure.
• QT Prolongation: Risk of torsades de pointes.
• Long-Term Toxicities: Fluorosis, periostitis, and increased risk of squamous cell carcinoma with prolonged use.

CYP2C19 Pharmacogenetics and Personalized Dosing

Genetic variations in CYP2C19 significantly affect voriconazole metabolism:

• Poor metabolizers (CYP2C19*2/*2): Higher drug levels, increased toxicity risk.
• Ultrarapid metabolizers (CYP2C19*17/*17): Lower drug levels, risk of treatment failure.
• Intermediate metabolizers (CYP2C19*1/*2): Require closer monitoring.

Personalized Dosing Strategies:

• TDM to maintain effective plasma concentrations (1-5.5 mcg/mL).
• Genetic testing to predict dose adjustments.

Conclusion

Voriconazole is a valuable antifungal agent, but its pharmacokinetics, drug interactions, and genetic variability require careful monitoring. Therapeutic drug monitoring and pharmacogenetic testing help optimize dosing, improve efficacy, and minimize toxicity. More about PGx testing and genomic medicine.

Disclaimer: This blog is for informational purposes. Always consult a healthcare professional for guidance on voriconazole therapy or before taking any medical action.