What is the recommended dose of fluconazole (antifungal medication) for pediatric patients?

Pediatric Fluconazole Dosing

For most pediatric fungal infections, fluconazole dosing is 6-12 mg/kg/day, with higher doses (12 mg/kg/day) required for invasive disease and lower doses (3-6 mg/kg/day) for mucosal infections, but neonates require special age-adjusted dosing intervals due to dramatically prolonged drug half-life. 1, 2

Age-Specific Dosing Framework

Neonates (Birth to 3 Months)

Neonates have fundamentally different pharmacokinetics with half-lives of 55-90 hours compared to 30 hours in adults, requiring extended dosing intervals rather than daily administration. 3

For Systemic Candida Infections:

• Gestational age ≥30 weeks: 25 mg/kg loading dose on day 1, then 12 mg/kg once daily 1
• Gestational age <30 weeks: 25 mg/kg loading dose on day 1, then 9 mg/kg once daily 1
• First 2 weeks of life (all neonates): Administer the standard dose every 72 hours 2, 4
• Weeks 2-4 of life: Administer the standard dose every 48 hours 4
• After 4 weeks: Daily dosing is appropriate 4

For Prophylaxis in High-Risk Neonates:

• Extremely low birth weight (<1000g) in NICUs with high invasive candidiasis rates (>10%): 3-6 mg/kg twice weekly for 6 weeks 5, 3
• This prophylaxis only applies to specific high-risk settings and is not treatment dosing 3

Infants and Children (3 Months to 17 Years)

Children over 1 year require approximately twice the adult mg/kg dose to achieve equivalent drug exposure due to increased clearance. 3

Oropharyngeal Candidiasis (Thrush):

• Loading dose: 6 mg/kg on day 1 1, 2
• Maintenance: 3 mg/kg once daily 1, 2
• Duration: Minimum 7-14 days, continuing at least 48 hours after symptom resolution 3, 6
• Critical pitfall: Single-dose therapy is never appropriate for documented fungal infections 3

Esophageal Candidiasis:

• Loading dose: 6 mg/kg on day 1 1, 2
• Maintenance: 3 mg/kg once daily, up to 12 mg/kg/day based on response 1, 2
• Duration: Minimum 3 weeks and at least 2 weeks after symptom resolution 1, 2

Systemic Candida Infections (Candidemia, Disseminated Candidiasis):

• Age ≥3 months: 25 mg/kg loading dose (maximum 800 mg), then 12 mg/kg once daily (maximum 400 mg) 1
• Duration: Minimum 3 weeks and at least 2 weeks after symptom resolution 1
• For treatment of invasive candidiasis, 12 mg/kg/day is necessary to achieve AUC >400 mg*h/L in >90% of preterm infants and 80% of term infants 7

Cryptococcal Meningitis:

• Acute treatment: 12 mg/kg on day 1, then 6-12 mg/kg once daily 3, 1, 2
• Duration: 10-12 weeks after CSF sterilization 3, 1, 2
• Maintenance/suppression (AIDS patients): 6 mg/kg once daily long-term 3, 1, 2

Prophylaxis in High-Risk Oncology/Transplant:

• Allogeneic HSCT: 8-12 mg/kg once daily from day 0 until day +75 post-transplant 5
• AML/recurrent leukemia: 8-12 mg/kg daily after last chemotherapy dose until neutrophil recovery 5
• Autologous HSCT: 8-12 mg/kg daily after last chemotherapy dose until neutrophil recovery (only for patients with expected profound neutropenia) 5
• Important caveat: Fluconazole prophylaxis should only be used in institutions with low mold infection rates or with active diagnostic algorithms for mold infections 5

Special Populations

Patients on ECMO:

• Age ≥3 months: 35 mg/kg loading dose (maximum 800 mg), then 12 mg/kg once daily (maximum 400 mg) 1
• Neonates <3 months, gestational age ≥30 weeks: 35 mg/kg loading dose, then 12 mg/kg once daily 1
• Neonates <3 months, gestational age <30 weeks: 35 mg/kg loading dose, then 9 mg/kg once daily 1

Renal Impairment:

• Give full loading dose initially (50-400 mg based on indication) 1, 2
• Creatinine clearance >50 mL/min: 100% of recommended dose 1, 2
• Creatinine clearance ≤50 mL/min (no dialysis): 50% of recommended dose 1, 2
• Hemodialysis: 100% of recommended dose after each dialysis session 1, 2
• If serum creatinine ≥1.3 mg/dL: Extend dosing interval to every 48 hours until creatinine normalizes 3, 7
• Dose adjustment is indicated if creatinine does not improve within 96 hours 7

Route of Administration

• Oral and IV routes are interchangeable with equivalent bioavailability 1, 2
• IV infusion rate: Maximum 200 mg/hour 1
• Oral administration: Can be taken with or without food 2

Therapeutic Drug Monitoring

• Target trough concentrations: 4-20 mcg/mL for treatment 4
• For prophylaxis: Maintain concentrations ≥2-4 mcg/mL for half the dosing interval 7
• TDM is particularly important in neonates due to highly variable pharmacokinetics 4

Common Pitfalls to Avoid

• Never use single-dose therapy for documented fungal infections - loading doses must always be followed by maintenance dosing 3
• Do not confuse prophylaxis regimens with treatment doses - prophylaxis doses (3-6 mg/kg twice weekly) are inadequate for active infection 3
• Do not use daily dosing in neonates <2 weeks old - extended intervals (every 72 hours) are required due to prolonged half-life 4
• Avoid fluconazole prophylaxis in institutions with high mold infection rates without active diagnostic algorithms, as fluconazole lacks mold coverage 5
• Monitor for drug interactions in patients on multiple medications, though clinical interactions are uncommon 8

Safety Profile

• Most common adverse effects: Gastrointestinal symptoms (7.7%) and skin reactions (1.2%) 8
• Hepatotoxicity: Transient transaminase elevations occur in 0.5-4.9% but are usually self-limiting 8
• Discontinuation rate: Only 3.2% of children discontinue due to adverse effects 8
• The safety profile in children mirrors the excellent safety profile seen in adults 8