Please note that much of the content on this page was created in 2010: the information provided may be out of date.
Important information: At no time should the information compiled here be used as a treatment protocol or for any other purpose except to provide the latest available summary of information relating to paediatric patients for educational and scientific purpose. We accept no liability for the use of data gathered here. Treatments should always be carried out according to manufacturers instructions. Not all antifungal treatments are licensed for use in paediatric patients.
UPDATE: In 2022, Groll, Roilides and Walsh published an update on the antifungal drugs under investigation or recently approved for paediatric fungal infections. While fluconazole, itraconazole and voriconazole have been available for some time, the table reproduced below outlines the more recent developments in paediatric treatment. [This summary has been reproduced from published data — it should not be substituted as a treatment protocol. Original references should be consulted. No liability will be undertaken by the Aspergillus website or its staff].
Compounds, Formulations, Dosages and Clinical Indications Approved or Targeted for Approval in Paediatric Patients (Groll, Roilides and Walsh, 2022)
| Antifungal Agent (Brand Name) | Formulation | Adult Dose | Pediatric Dosage | Approved or Targeted Pediatric Indications |
|---|---|---|---|---|
| Posaconazole (Noxafil®) | Posaconazole intravenous solution delayed-release tablets oral suspension powder for delayed release oral suspension | 300 mg once daily (day 1: twice daily) 300 mg once daily (day 1: twice daily) 200 mg three times daily (≥ 13 yr [FDA]) Not approved | ≥ 2 yr old: 6 mg/kg once daily (maximum 300 mg; day 1: twice daily) >40 kg: 300 mg once daily (day 1: twice daily) Not approved (EMA) ≤40 kg: weight-based once daily dosing (day 1: twice daily). For details, see SPC. | Prophylaxis in high-risk patients receiving remission-induction chemotherapy for AML or MDS expected to result in prolonged neutropenia, and HSCT recipients who are undergoing high-dose immunosuppressive therapy for GVHD (EMA)/Prophylaxis of invasive Aspergillus and Candida infections in high risk patients including HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy (FDA).Treatment of invasive aspergillosis (EMA/FDA; targeted). |
| Anidulafungin (U.S.: Eraxis®; E.U.: Ecalta®) | Anidulafungin intravenous solution | 100 mg once daily (day 1: 200 mg) | ≥ 1 mo old: 1.5 mg/kg (not to exceed 100 mg) of anidulafungin once daily (day 1: 3.0 mg/kg; not to exceed 200 mg) | Treatment of invasive candidiasis (EMA)/Treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and peritonitis) (FDA). |
| Investigational: | ||||
| Isavuconazole (Cresemba®) | Isavuconazonium sulfate oral capsules intravenous solution | 372 mg isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) once daily (days 1 and 2: three times daily) | ≥ 1 yr old: 10 mg/kg of isavuconazonium sulfate once daily (days 1 and 2: three times daily); investigational | Treatment of invasive aspergillosis (EMA/FDA); targeted. Treatment of invasive mucormycosis (FDA) in patients for whom amphotericin B is inappropriate (EMA); targeted. |
The table below, created in 2010, outlines the use of antifungal treatment and outcomes for Invasive Aspergillosis, with a summary of notable factors in children.
[*This summary has been compiled from published data — it should not be substituted as a treatment protocol. Original references should be consulted. Not all antifungal drugs are licensed for paediatric use; no liability will be undertaken by the Aspergillus website or its staff.]
| Drug | Target fungal infections | Dose per day | Pharmacokinetics | Important notes |
|---|---|---|---|---|
| Polyenes | Binds ergosterol in fungal cell membrane | |||
| Amphotericin B deoxycholate | Candidiasis Cryptococcal meningitis | 0.7- 1.0 mg/kg daily over 2-4 h [1] | Similar to adult | High individual variation, renal toxicity. |
| Amph B lipid formulations: Abelcet AmBisome Amphocil | Candidiasis Aspergillosis Zygomycosis | 3-5mg/kg daily for lipid forms, 3-4 mg/kg for colloidal [2] | Safety data same as adult | Less renal toxicity than Amphotericin B parent compd. Less fever, chills and rigors |
| Antimetabolites | Inhibitor of pyrimidine salvage pathway | |||
| 5-fluorocytosine | Candidiasis (in combination with Amphotericin B) | 100mg/kg (in four doses) day Peak plasma levels for antifungal active 40-60 ug/ml [3] | Insufficient data in childrenneonates? | Variable drug clearance data |
| Triazoles | Inhibits lanosterol 14- a- demethylase | |||
| Fluconazole | Candida, Cryptococcus, Dermatophyte infection | 12 mg/kg for neonates and 12 mg/kg in paediatric patients. [4] | See Groll table 2 | Greater plasma clearance with shorter 1/2 life( not in premature) side effects include gastro intest disturbances and hepatic transaminase levels increased. |
| Itraconazole | Candida Aspergillus Dermatophyte infection | Oral soln >2yrs suggest starting dose 5mg/kg in 2 doses daily (to attain trough level of 0.5ug/ml [5] IV data lacking | In immunocompromised patients only here | Adverse effects vomiting, abnormal liver function, abdominal pain*itra not approved for<18yrs so off label |
| Voriconazole | Invasive Aspergillosis Fusarium Scedosporium Candidiasis in non- neutropenics | 9 mg/kg/dose IV load day 1, then 8 mg/kg/dose or 9 mg/kg/dose PO maintainance. If >12 years, then load 6 mg/kg/dose and the 4 mg/kg/dose or give 200-300 mg PO per dose *1 | Immunocompromised paediatrics with invasive mycosis – has approval from FDA Table 3 Groll (?) No data for <2 yrs so empirical . | Ages 2-11 have higher elimination rates than adult which may result in lower non therapeutic doses. No data <2 yrs on pharmacokinetics |
| Posaconazole | Active against zygomycetes, broad spectrum. Approved 2nd line treatment for:aspergollosis fusariosis, chrmoblastomycosis coccidioidomycosis >18yrs. Approved prophylaxis for AML , myelodysplasia, hematopoietic, GVHD and stem cell transplant | No pharmacokinetcs <18yrs. In 12 patients less than 8yrs no basic differences in trough levels. Successful salvage reported in 5/11 and 6/10 with IF ie. similar to adult. Dosage safety and tolerance has been initiated by manufacturers for paediatrics. [6] | ||
| Echinocandins | Inhibit 1,3 beta-D glucan synth in fungal cell wall | |||
| Anidulafungin | In adults licensed for candida | 0.7-1.5mg/kg/day in children. Study of 19 granulocytopenic children w cancer similar to adults re plasma conc. [7] | No serious side effects in paediatric trial of cancer patients | |
| Caspofungin | Candida Aspergillus | 50mg/m2 daily(70 mg day 1)for 3months –17yrs [8]. In 0-3months, 25mg/m2 gave same exposure as for 3 month-17yrs. [9] | Very few serious side effects well tolerated, favourable safety profile. Success rates comparable to Amph B lipo. | |
| Micafungin | 100 mg/day <40 kg weight(2mg/kg) or 150 mg /day(4mg/kg), for oesophageal candidiasis and 50 mg/day for prevention. [10] | Licensed in EU for invasive candida and as prophylaxis for candida with allogeneic stem cell tr Similar to adults | In Neonates micafungin has a shorter half life – clearance is more rapid, so need a larger dose. Recommend 4mg/kg in neonates with invasive candidiasis, higher dose 10 mg/kg with CNS involvement. Recommend liver monitoring (Alanine transaminase & Aspartate transaminase) during treatment |
Data is mainly compiled from Groll & Tragiannidis 2010.
This website specialises in Aspergillus infections. However, the lack of paediatric data means that we have included data for other types of fungal infections where it may be useful.
*1 W. Steinbach, personal communication.