What is the recommended oral dose of Voriconazole (antifungal medication) for adults and pediatric patients?

Recommended Oral Dosing of Voriconazole for Adults and Pediatric Patients

For adults, the recommended oral voriconazole dosing is 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. 1, 2

Adult Dosing

Loading Dose

• 400 mg (6 mg/kg) twice daily for the first day (2 doses total) 3, 1
• This loading dose achieves therapeutic concentrations rapidly 2

Maintenance Dose

• 200-300 mg (3-4 mg/kg) twice daily 3, 1, 2
• The 200 mg oral dose provides exposure similar to 3 mg/kg IV dose 2
• The 300 mg oral dose provides exposure similar to 4 mg/kg IV dose 2
• For patients weighing less than 40 kg, the maintenance dose should be halved (100-150 mg twice daily) 2

Dose Adjustments

• If patient response is inadequate, the oral maintenance dose may be increased from 200 mg to 300 mg twice daily 2
• If patient cannot tolerate 300 mg twice daily, reduce by 50 mg steps to a minimum of 200 mg twice daily 2
• For patients with mild to moderate hepatic impairment (Child-Pugh Class A and B), use standard loading dose but halve the maintenance dose 2
• No dosage adjustment is necessary for patients with renal impairment when using oral voriconazole 3, 2

Pediatric Dosing

Adolescents (12-14 years, ≥50 kg) and Patients 15 years and older

• Use adult dosing regimen 2

Children and Adolescents (2-14 years, <50 kg)

• Higher doses may be required in pediatric patients due to accelerated metabolic clearance 3
• The European Medicines Agency recommends a maintenance dosage of 7 mg/kg twice daily in pediatric patients to attain plasma levels comparable to those of adults 3

Administration Considerations

Food Effects

• Oral bioavailability of voriconazole is excellent (>90%) 1
• Bioavailability decreases when administered with food 3
• For optimal absorption, take at least 1 hour before or after a meal 3

Alternative Administration

• Crushed tablets are bioequivalent to whole tablets, making this a viable option for patients who have difficulty swallowing 4
• When tablets are crushed, absorption may be slightly faster (time to maximum concentration 0.5h vs 1.5h) 4

Clinical Considerations

Therapeutic Drug Monitoring

• Due to high interpatient variability in voriconazole exposure, therapeutic drug monitoring may be beneficial, especially with oral therapy 3, 5
• Common polymorphisms in CYP2C19 can result in wide variability of serum levels 3, 1

Duration of Therapy

• For candidemia without metastatic complications, treat for 2 weeks after documented clearance of Candida from bloodstream and resolution of symptoms 1
• For invasive aspergillosis, the median duration in clinical trials was 76 days of oral therapy following initial IV treatment 1

Common Side Effects

• Visual disturbances (approximately 30% of patients) 6
• Hepatic injury 1
• Photosensitivity 1
• Periostitis with prolonged use (due to fluoride release during metabolism) 7

Important Precautions

• Voriconazole should not be used for urinary candidiasis as it does not accumulate in active form in the urine 3, 1
• Drug-drug interactions are common with voriconazole and should be carefully evaluated before initiating therapy 3, 1
• Oral voriconazole is preferred over IV formulation in patients with renal dysfunction (creatinine clearance <50 mL/minute) 3, 1
• Voriconazole is the only triazole that requires dosage reduction for patients with mild to moderate hepatic impairment 3