Pharmacokinetics in children

Posaconazole is slowly absorbed following oral administration. Plasma protein binding to albumin is high, exceeding 98% [Krishna 2007, SmPC Noxafil]. Metabolism occurs primarily via UDP-glucuronidation (UGT1A4) [Chen 2020]. From six months of age onward, UGT1A4 gene expression is present, although its enzymatic activity may continue to increase until approximately 1.4 years of age [Miyagi 2007] [Strassburg 2002]. Posaconazole is mainly eliminated as the unchanged parent compound in feces [Krishna 2007] [SmPC Noxafil].

There is interindividual variability in posaconazole PK, particularly during the absorption phase and when using the regular oral suspension formulation in pediatrics. In general, higher gastric pH and increased gastrointestinal motility decrease the bioavailability of the oral suspension by reducing the solubility and shortening gastric residence time [Chen 2020]. In pediatric patients receiving the oral suspension, relative bioavailability was up to 1.95 times higher when taken with a high-fat meal compared to regular food [Lin 2022]. Additionally, concomitant use of proton pump inhibitors significantly reduced the bioavailability of the suspension, with reductions ranging from 41.0% to 75% [Kane 2023] [McCann 2023] [Boonsathorn 2019] [Elkayal 2021]. Diarrhea has also been associated with a 33% decrease in suspension bioavailability [Boonsathorn 2019] [Elkayal 2021].

The following PK parameters were found at steady state after administration of posaconazole oral suspension at a dose of 13.8 mg/kg/day divided into three doses in 14 children aged 2 to 13 years: a Cmax of 0.96 ± 0.63 mg/mL and a CL of 0.8 L/kg/h [Vanstraelen 2016].

In 12 pediatrics aged 8 to 17 years, posaconazole oral suspension was given at a total daily dose of 800 mg divided for treatment of invasive fungal infections. Mean plasma concentrations (776 ng/mL) were comparable to those observed in 194 adult patients aged 18 to 64 years (817 ng/mL). Similarly, in prophylaxis studies, the mean steady-state average concentration (Cav) in adolescents (13–17 years) was similar to that in adults (≥18 years) [Krishna 2007] [SmPC Noxafil].

In 42 pediatrics, children aged 3 to 10 years required higher doses of oral suspension compared to children older than 13 years (13.0 vs. 6.0 mg/kg) [Kassa 2025].

In a cohort of 136 neutropenic children aged 3 months to 18 years, posaconazole oral suspension was administered at doses up to 18 mg/kg/day divided three times daily. Approximately 50% of patients achieved the predefined target range for Day 7 Cav (500–2500 ng/mL). Drug exposure tended to be higher in older children (7 to <18 years) compared to younger ones (2 to <7 years) [Arrieta 2019] [SmPC Noxafil]:

aMedian (min-max). bArithmetic mean (%CV, SD) The following PK data from PopPK studies were obtained in (immunocompromised) children (0.4-18.5 years) undergoing prophylaxis or treatment for invasive fungal infection using tablet, suspension, or IV formulations.

RSE, relative standard error; CLsat, maximum (or saturated) rate of clearance; V, volume of distribution; F, bioavailability; CL/F, apparent clearance; V/F, apparent volume; D50, dose at which F is 50%; PPI, proton pump-inhibitor; OME, omeprazole; PAN, pantoprazole All disposition terms are centered on a fully mature 70-kg individual using allometric scaling with exponents of 1 for volume and 0.75 on CLsat. 1Saturated rate of clearance; 2CL/F and V/F were related to the tablet formulation (F=1); 3V/F may be overestimated due to the absence of a reference formulation; F is not explicitly estimated

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

No clear toxicity threshold for serum levels has been established to date.

The most commonly reported adverse events are gastrointestinal symptoms, including nausea, vomiting, diarrhea, and abdominal pain, particularly with oral formulations [Arrieta 2019] [Weerdenburg 2024] [Lehrnbecher 2010] [Gwee 2015]. Incidence rates vary widely (6–57%), but these events rarely lead to treatment discontinuation [Weerdenburg 2024].

Hepatotoxicity is frequently observed, with transaminitis reported in 20–51% of patients. In some studies, this led to discontinuation in up to 31% of cases. Liver enzyme elevations ranged from grade I to III [Lin 2022] [Weerdenburg 2024].

Kassa [2025] identified hypertension as a potential side effect in pediatric allo-HSCT recipients, occurring in 41.2% of patients, often without other identifiable causes. Although no strong correlation with posaconazole levels was found, this finding suggests the need for monitoring blood pressure alongside liver function.

Other reported adverse events include skin reactions (up to 12%), headache, and fever, mostly mild and transient. (Severe) hypokalemia is also an observed side effect [Jia 2022] [Barton 2018]. No consistent relationship has been found between posaconazole plasma concentrations and the occurrence or severity of adverse effects [Weerdenburg 2024].

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

The bioavailability of posaconazole is strongly influenced by food intake and acidity. Therapeutic drug monitoring (TDM) seems appropriate in this case. The SWAB uses the following levels (in adults):
- Therapy: trough level > 1 mg/mL;
- Salvage therapy trough >1.5 mg/mL, determine level after 5-7 days (steady state);
- Prophylaxis: trough level > 0.7 mg/mL

Given the occurrence of unexplained hypertension in pediatric allo-HSCT patients, routine monitoring of both liver function and blood pressure is recommended [Kassa 2025].

In cases where food cannot be tolerated, a nutritional supplement may be used when administering the oral suspension (40 mg/ml) [SmPC Noxafil].

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• ANTIINFECTIVES FOR SYSTEMIC USE
• ANTIMYCOTICS FOR SYSTEMIC USE

ANTIMYCOTICS FOR SYSTEMIC USE

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

References

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Changes

Therapeutic Drug Monitoring

Overdose