What is the typical dosing regimen for voriconazole in the treatment of fungal infections?

Voriconazole Dosing

For invasive fungal infections in adults, initiate voriconazole with a loading dose of 6 mg/kg IV every 12 hours for two doses (day 1), followed by a maintenance dose of 4 mg/kg IV every 12 hours, which can be switched to 200 mg oral every 12 hours once the patient is clinically stable. 1, 2

Standard Dosing Regimen

Intravenous Administration

• Loading dose: 6 mg/kg IV every 12 hours for the first 24 hours (two doses total) 1, 2
• Maintenance dose: 3-4 mg/kg IV every 12 hours 1, 2
  • Use 4 mg/kg every 12 hours for invasive aspergillosis, scedosporiosis, and fusariosis 2
  • Use 3-4 mg/kg every 12 hours for candidemia and deep tissue candida infections (dose based on severity) 2
• Continue IV therapy for at least 7 days before considering transition to oral 1, 2

Oral Administration

• Loading dose: 400 mg (6 mg/kg) orally every 12 hours for two doses on day 1 1, 3, 2
• Maintenance dose: 200 mg orally every 12 hours 1, 3, 2
  • The 200 mg oral dose achieves exposure similar to 3 mg/kg IV 3, 2
  • The 300 mg oral dose achieves exposure similar to 4 mg/kg IV 3, 2
• Critical: Administer at least 1 hour before or after meals, as food decreases bioavailability 3, 2

Switching Between IV and Oral

• Oral bioavailability exceeds 90%, allowing seamless transition between formulations once the patient is clinically improved and can tolerate oral medication 1, 3, 2

Dose Adjustments

For Inadequate Response

• Increase oral maintenance dose from 200 mg to 300 mg every 12 hours 2
• For patients weighing <40 kg, increase from 100 mg to 150 mg every 12 hours 2

For Intolerance

• Reduce oral dose by 50 mg increments to a minimum of 200 mg every 12 hours (or 100 mg every 12 hours if <40 kg) 2
• Reduce IV maintenance dose from 4 mg/kg to 3 mg/kg every 12 hours 2

Patients Weighing <40 kg

• Administer half of the standard oral maintenance dose 2

Special Population Considerations

Renal Impairment

• IV formulation: Contraindicated in patients with creatinine clearance <50 mL/min due to cyclodextrin accumulation 1, 3
• Oral formulation: No dosage adjustment required for any degree of renal insufficiency 1, 3
• Recommendation: Strongly prefer oral voriconazole in patients with renal dysfunction 3

Hepatic Impairment

• Reduce maintenance dose by 50% in patients with mild to moderate hepatic impairment 3, 2
• Voriconazole is the only triazole requiring hepatic dose adjustment 3

Drug Interactions

• With phenytoin or efavirenz: Increase voriconazole maintenance dose 2
• Common CYP2C19 polymorphisms cause wide variability in serum levels 3
• Extensive drug-drug interactions occur; carefully evaluate all concomitant medications 3

Duration of Therapy by Indication

Invasive Aspergillosis

• Median duration in clinical trials: 10 days IV followed by 76 days oral therapy 1, 3
• Continue for a minimum of 6-12 weeks 1
• In immunosuppressed patients, continue throughout immunosuppression period and until lesions resolve 1

Candidemia and Deep Tissue Candida Infections

• Treat for at least 14 days after documented clearance from bloodstream AND resolution of symptoms 1, 3, 2
• Obtain daily or every-other-day blood cultures until clearance is documented 1

Esophageal Candidiasis

• Minimum 14 days AND at least 7 days following symptom resolution 2

Aspergillus Skin and Soft Tissue Infections

• Treat for 6-12 weeks 1

Therapeutic Monitoring

When to Monitor

• Therapeutic drug monitoring is beneficial due to high interpatient variability, especially with oral therapy 3
• Target trough concentrations: 1-4 mcg/mL (levels <1 mcg/mL associated with decreased efficacy; >4 mcg/mL with increased toxicity) 4
• Using dose modification protocols, 80% of patients achieve therapeutic range by the second adjustment 4

Patient-Specific Risk Factors for Subtherapeutic Levels

• Age ≤30 years and BMI ≤25 kg/m² have higher rates of subtherapeutic levels 4

Common Adverse Effects and Monitoring

Expected Side Effects

• Transient visual disturbances occur in approximately 30% of patients 1, 5
• Hepatic injury, photosensitivity, periostitis, and CNS effects 3
• Skin rashes in approximately 6% 5

Safety Profile

• Voriconazole is generally better tolerated than amphotericin B with significantly fewer treatment-related adverse events 1, 5
• Treatment discontinuation due to adverse effects occurs in <10% of patients 6

Critical Contraindications and Caveats

Do NOT Use For:

• Urinary candidiasis—voriconazole does not accumulate in active form in urine 3

Preferred Indications:

• CNS aspergillosis (achieves >50% of serum concentration in CSF) 3
• Step-down therapy for C. krusei and fluconazole-resistant, voriconazole-susceptible C. glabrata 3
• Fusarium species infections (high-dose IV voriconazole) 1
• Scedosporium apiospermum infections 1