Table 2.

Pertinent antifungal dosing, clinical pearls, and potential places in therapy

Drug	Doses utilized	Notable PK parameters	Likely place in therapy	Other Pearls
Amphotericin B deoxycholate IV [50–53]	Neonatal: 1 mg/kg qday Children: 0.25–0.5 mg/kg, can be titrated to 1.5 mg/kg qday	Vd: 0.38–3.99 L/kg Neonatal CNS penetration reported to be 40–90%13 Children CNS penetration is poor Excretion: urinary T ½: 14.8 (5 to 82 h) in neonates 11.9–48 h in children and adults	Invasive candidiasis in the neonatal population	Can give a test dose prior to administration Infusion-related reactions are common. Pre-medicate with an NSAID/acetaminophen ± diphenhydramine or hydrocortisone mono-therapy 30 to 60 min prior to drug administration. Rigors can be treated with meperidine Nephrotoxicity can occur during treatment. Adequate hydration and monitoring of kidney function are required. Neonates are reported to have less nephrotoxicity than adults
Amphotericin B (liposomal) IV [53–55]	Neonatal: 3–5 mg/kg qday (NON CNS) Children: 3–5 mg/kg qday	Vd: 0.1–0.16 L/kg CNS penetration: 1–3% Excretion: urine and feces T ½: 6–23 h	Resistant Candida infections Empiric therapy for neutropenic patients Invasive Aspergillus	Drug can have increased terminal half-life due to slow redistribution from tissues Dosing is not interchangeable between traditional and liposomal product Less infusion reactions and nephrotoxicity compared to traditional amphotericin
Fluconazole IV, tablet, suspension [10, 21, 56–58]	Neonatal: treatment: 12–25 mg/kg loading dose, then 6–12 mg/kg qday Prophylaxis: 3–6 mg/kg/dose twice weekly Children: 6–12 mg/kg loading dose 3–12 mg/kg qday	Vd: 0.913 L/kg CNS penetration: 50–90% Excretion: urine T ½: 20–50 h (dependent upon renal function)	Prophylaxis Invasive candidiasis Meningitis Urinary tract infections	Inhibits CYP 3A4, 2C9, and 2C19 enzymes Candida krusei demonstrates intrinsic resistance Can cause QT prolongation
Posaconazole IV, delayed-release tablet, and suspension [59, 60]	All data limited Oral suspension: infants ≥ 6 months to < 2 years: initial dosing: 200 mg QID 2–6 years: initial dosing: 200 mg QID Children 7–12 years: initial dosing: 300 mg/dose QID Oral delayed-release tablets: children 7–12 years: initial dosing: 200 mg/dose TID IV: VERY LMITED DATA Children ≤ 11 years: 6–10 mg/kg BID on day 1, followed by 6–10 mg/kg daily (maximum dose 300 mg)	Vd: oral: 287 L; IV: 261 L CNS penetration: limited data, thought to be poor Excretion: feces 71%, 13% urine T ½: suspension: ~35 h Tablets: 26 to 31 h IV: ~ 27 h	Aspergillus prophylaxis Maintenance and salvage therapy for mucormycosis	Oral suspension has better absorption with a high-fat meal or if taken with an acidic beverage Displays saturable absorption Tablet has more predictable absorption than liquid suspension Trough goals are typically > 0.7 mg/L for prophylaxis and 1 mg/L for treatment Concentration recommended to be drawn on day 7 of therapy Inhibits the CYP 3A4 enzyme
Vonconazole IV, tablet, and suspension [60–63]	Neonatal: Limited data case reports: IV: 12 to 20 mg/kg/day divided every 8 to 12 h Children 2 to < 12 years: IV: 9 mg/kg q12 h for 2 doses on day 1 followed by IV: 8 mg/kg/dose every 12 h or PO suspension 9 mg/kg q12 h Children ≥ 12 to ≤ 14 years: < 50 kg: IV loading dose:9 mg/kg/dose q12 h for 2 doses; followed by 4 to 8 mg/kg q12 h ≥ 50 kg: IV loading dose: 6 mg/kg q12 h for 2 doses followed by 3 to 4 mg/kg q12 h Oral maintenances: < 50 kg: 9 mg/kg/q12 h ≥ 50 kg: 200 mg every 12 h Adolescents ≥ 15 years: IV: loading dose: 6 mg/kg q12 h for 2 doses; followed by 3 to 4 mg/kg q12 h Oral maintenance: < 40 kg: 100 mg q12 h ≥ 40 kg: 200 mg q12 h	Vd: Diphasic in children 2 to < 12 years 0.81 mL/kg (central) 2.2 mL/kg (peripheral)12 CNS penetration: 68–100% Non-linear kinetics (most likely Michaelis-Menten) Adults: 4.6 L/kg Excretion: urine T ½: dose dependent, steady state reached on day 3 with loading dose and by day 5–8 without	Invasive Aspergillus Salvage therapy for mold infections	Can cause photopsia, neurotoxicity, rash, QT prolongation, hepatotoxicity, and nephrotoxicity (IV product has a cyclodextrin solvent, albeit debated toxicity) Oral formulations have erratic absorption and need to be separated from food. Switch to oral only recommended after significant clinical improvement Trough level goals of 1–5.5 mg/L. Levels of 2–6 mg/L can be targeted if CNS involvement Dose adjustments are non-linear, meaning changes in trough/AUC may not be proportional to changes in dosage Is a substrate for and inhibits CYP 3A4, 2C9, and 2C19 enzymes
Amdulafungin IV [60, 61, 64, 65]	Neonatal: Limited data based off of pharmacokinetic study IV: 3 mg/kg once on day 1, then 1.5 mg/kg qday15 Children: IV: 1.5–3 mg/kg once on day 1, then 0.75–1.5 mg/kg qday (max 200 mg)	Vd: 30 to 50 L CNS penetration: Negligible Excretion: primarily feces T ½: 40 to 50 h	Invasive candidiasis	Monitor liver function tests Not routinely used for urinary tract infections
Caspofungin IV [60, 61]	Neonatal: Limited data IV: 25 mg/m2 qday or 2 mg/kg qday Children: 70 mg/m2 qday on day 1, then 50 mg/m2 qday	Vd: unknown, non-linear kinetics CNS penetration: negligible Excretion: 41% urine; feces 35% T ½: terminal 40–50 h	Systemic candidiasis Salvage therapy for Aspergillus	AUC increased with either renal or hepatic impairment Drug accumulates due to non-linear kinetics Can cause chills and hypotension on infusion Monitor Liver function tests periodically
Micafungin IV [36••, 60, 61, 66–68]	Neonatal: 4–10 mg/kg qday Children: IV: 2–3 mg/kg qday	Vd: highly variable with age CNS penetration: negligible Primarily hepatic metabolism Excretion: primarily feces T ½ 6.7–21 h	Systemic candidiasis Prophylaxis Salvage therapy for Aspergillus	Monitor liver function tests Not routinely used for urinary tract infections Higher doses are often needed for neonates and younger children due to pharmacokinetic differences Higher doses are needed for CNS infections