What is the recommended oral dose of Voriconazole (antifungal medication) for treating fungal infections?

Voriconazole Oral Dosing

For oral voriconazole, administer a loading dose of 400 mg (6 mg/kg) twice daily for 2 doses on day 1, followed by a maintenance dose of 200-300 mg (3-4 mg/kg) twice daily, taken at least one hour before or after meals. 1, 2, 3

Standard Dosing Regimen

Loading Phase

• Day 1: 400 mg orally every 12 hours for 2 doses 1, 2
• This loading dose is equivalent to 6 mg/kg for a 70 kg patient 1

Maintenance Phase

• Day 2 onwards: 200-300 mg orally every 12 hours 1, 2, 3
• The 200 mg oral dose achieves exposure similar to 3 mg/kg IV 1, 3
• The 300 mg oral dose achieves exposure similar to 4 mg/kg IV 1, 3
• Select the higher maintenance dose (300 mg) for more severe infections or inadequate response 3

Administration Requirements

• Must be taken at least 1 hour before or after meals to optimize absorption, as bioavailability decreases significantly with food 1, 3
• Oral bioavailability exceeds 90%, allowing seamless transition between IV and oral formulations 1

Dose Adjustments

For Inadequate Response

• Increase from 200 mg every 12 hours to 300 mg every 12 hours 3
• For patients weighing less than 40 kg, increase from 100 mg to 150 mg every 12 hours 3

For Intolerance

• Reduce by 50 mg increments to a minimum of 200 mg every 12 hours (or 100 mg every 12 hours if weight <40 kg) 3

Hepatic Impairment

• Reduce maintenance dose by 50% in patients with mild to moderate hepatic impairment (Child-Pugh class A or B) 1, 2
• Voriconazole is the only triazole requiring hepatic dose adjustment 1

Renal Impairment

• No dosage adjustment necessary for oral voriconazole regardless of creatinine clearance 1, 2
• Oral formulation is strongly preferred over IV in patients with CrCl <50 mL/min, as the IV formulation is contraindicated due to cyclodextrin accumulation 2, 4

Duration by Indication

Invasive Aspergillosis

• Median duration in clinical trials: 10 days IV followed by 76 days oral therapy 1, 2
• Minimum treatment duration: 6-12 weeks 2

Candidemia and Deep Tissue Candida Infections

• Treat for at least 14 days after documented clearance from bloodstream AND resolution of symptoms 1, 2, 3

Esophageal Candidiasis

• Minimum 14 days and at least 7 days following symptom resolution 3

Critical Contraindications and Caveats

Do Not Use For:

• Urinary candidiasis: Voriconazole does not accumulate in active form in urine 1, 2

Preferred Indications:

• CNS aspergillosis (achieves >50% of serum concentration in CSF) 1, 2
• Step-down therapy for C. krusei and fluconazole-resistant, voriconazole-susceptible C. glabrata 1, 2
• Fusarium species and Scedosporium apiospermum infections 2, 3

Monitoring Considerations

Therapeutic Drug Monitoring

• Strongly consider TDM due to high interpatient variability in voriconazole exposure, especially with oral therapy 1
• CYP2C19 polymorphisms cause wide variability in serum levels 1

Common Adverse Effects

• Visual disturbances (approximately 30% of patients, typically transient) 1, 5
• Hepatic enzyme elevations (up to 20%) 4
• Photosensitivity, skin rashes (approximately 6-20%) 1, 5, 4
• Periostitis and CNS side effects 1

Drug Interactions

• Extensive drug-drug interactions due to CYP2C19, CYP3A4, and CYP2C9 metabolism 1, 4
• Increase dose when co-administered with phenytoin or efavirenz 3

Special Populations

Pediatric Patients (12-14 years, ≥50 kg; or ≥15 years regardless of weight)

• Use adult dosing regimen 3
• Higher doses may be required in younger pediatric patients due to accelerated metabolic clearance 1

Patients <40 kg

• Reduce maintenance dose to 100 mg every 12 hours (may increase to 150 mg if inadequate response) 3