Isavuconazole Treatment for Invasive Fungal Infections in Pediatric Patients
Abstract
:1. Introduction
2. Results
2.1. Safety in Curative Use
2.2. Safety in Prophylaxis Use
2.3. Clinical Response
3. Discussion
4. Materials and Methods
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Fungal Infection | Sex, Age (y), Weight (kg) | Hematologic Disease | ISA Initial DoseRoute | Co-Antifungal | Drugs Metabolized by CYP3A4 | Time to First ISA Level (days) | First ISA Ctrough (mg/L) | Capsules Opened at Any Time | Total Days of ISA | Median ISA Ctrough (mg/L) | Modification of Dosage | Balanced Dosage mg/day | IFI Response at Day 15 | IFI Response at Day 90 | AST Spike (UI/L) | ALT Spike (UI/L) | Scr h Spike (µM) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Proven mucor a | F 5.4 y 20 kg | ALCL c | 100 mg IV | L-AmB e | lorlatinib | 5 | 1.77 | NO | 105 | 2.14 | Increased, 2 times | 200 | partial | complete | 33 | 15 | 72 |
Proven mucor a | M 6.5 y 19 kg | B-ALL | 100 mg IV | L-AmB e | NA | 3 | 2.77 | NO | 64 | 2.58 | Increased, 3 times | 200 | stable | partial | 269 | 339 | 42 |
Proven mucor a | M 2.4 y 13 kg | B-ALL | 100 mg Oral | L-AmB e | NA | 9 | 1.6 | YES | 276 | 2.30 | Increased, 1 time | 130 | stable | complete | 34 | 22 | 55 |
Proven Asp b flavus | F 10.9 y 30 kg | T-ALL | 100 mg IV | CASP f | CsA g | 8 | 0.73 | NO | 356 | 3.22 | Increased, 1 time | 200 | stable | complete | 59 | 83 | 29 |
Probable Asp b fumigatus | F 2.4 y 12 kg | B-ALL | 100 mg Oral | NA | CsA g | 7 | 1.79 | YES | 74 | 0.88 | NA | 100 | partial | complete | 59 | 35 | 22 |
Probable Asp b fumigatus | M 9.1 y 37 kg | Fanconi anemia | 200 mg Oral | NA | CsA g | 5 | 3.87 | NO | 15 | 3.72 | NA | 200 | partial | partial | 98 | 79 | 56 |
Probable Asp b fumigatus | M 11.2 y 30 kg | Burkitt ALL | 200 mg IV | NA | NA | 4 | 3.29 | NO | 95 | 4.76 | NA | 200 | stable | complete | 399 | 394 | 46 |
Probable Asp b fumigatus | M 9.1 y 29 kg | B-ALL | 100 mg Oral | NA | NA | 5 | 4.2 | NO | 65 | 5.00 | NA | 100 | partial | complete | 258 | 234 | 35 |
Probable Asp b fumigatus | F 5.3 y 15 kg | MDS d | 100 mg IV | CASP f | venetoclax/CsA g | 3 | 5.12 | NO | 81 | 3.19 | Increased, 2 times | 140 | partial | partial | 18 | 7 | 30 |
Prophylaxis | F 4.6 y 18 kg | AML | 100 mg IV | NA | sorafenib/CsA g | 2 | 3.8 | YES | 240 | 2.77 | NA | 100 | NA | NA | 64 | 72 | 30 |
Prophylaxis | M 15.3 y 48 kg | Fanconi anemia | 200 mg Oral | NA | CsA g | NA | NA | NO | 253 | NA | NA | 200 | NA | NA | 108 | 105 | 50 |
Prophylaxis | M 15.6 y 58 kg | T-ALL | 200 mg Oral | NA | CsA g | 7 | 4.7 | NO | 119 | 2.95 | NA | 200 | NA | NA | 43 | 92 | 79 |
Prophylaxis | M 10.1 y 35 kg | Aplastic anemia | 200 mg IV | NA | CsA g | 4 | 2.51 | NO | 183 | 2.93 | Decreased, 2 times/increased 1 time | 100 | NA | NA | 19 | 54 | 51 |
Prophylaxis | F 14.5 y 61 kg | Aplastic anemia | 200 mg Oral | NA | CsA g | 2 | 3.35 | NO | 109 | 3.29 | NA | 200 | NA | NA | 53 | 114 | 40 |
Prophylaxis | M 8.1 y 25 kg | B-ALL | 100 mg Oral | NA | CsA g | 3 | 3.51 | NO | 15 | 2.81 | NA | 100 | NA | NA | 20 | 12 | 15 |
Authors and Date of Publication | No a of Patients | No a of Patients <30 kg | Age (Median y b), Weight (Median kg) | ISA Dose Patients <30 kg | ISA Dose Patients >30 kg | Median ISA Ctrough (mg/L) | Median ISA Ctrough (mg/L) Patients < 30 Kg | Median ISA Ctrough (mg/L) Patients >30 Kg | Total Days of ISA (Range) | IFI Response at Day 90 | No a of Patients with AST >3 Times Upper Limit | No a of Patients with ALT >3 Times Upper Limit | No a of Patients with Scr c >1.5 Times Baseline |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Decembrino et al. 2020 [6] | 29 | 7 | 14.5 y, 47 Kg | 100 mg/day | 200 mg/day | 4.91 (2.15–8.54) | 1.1 (0.73–2.15) | 5.0 (2.48–8.54) | 6–523 | 12/29 complete | 2/29 | NA | 3/29 spike |
Ross et al. 2020 [11] | 18 | 4 | 12.5 y, 50.2 kg | 100 mg/day | 200 mg/day | 3.6 (0.4–7.4) | 3.7 (3.2–5.6) | 2.7 (0.4–7.4) | 55 | 6/18 complete | 4/18 | 1/18 | 2/18 |
Arrieta et al. 2021 [10] | 46 | - | 11 y, 38 Kg | 200 mg/day | 200 mg/day | NA | NA | NA | 1–26 | NA | NA | NA | NA |
Ashkenazi-Hoffnung et al. 2020 [7] | 4 | 1 | 10.5 y 40 kg | 5.4 mg/kg/day | 200 mg/day | NA | NA | NA | 60–115 | 4/4 complete | NA | NA | NA |
Barg et al. 2018 [8] | 3 | 2 | 5 y, 18.5 kg | 100–200 mg/day | 200 mg/day | 2.32 | 2.32 (0.98–6.04) | NA | 42–236 | 3/3 complete | NA | NA | NA |
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Zimmermann, P.; Brethon, B.; Roupret-Serzec, J.; Caseris, M.; Goldwirt, L.; Baruchel, A.; de Tersant, M. Isavuconazole Treatment for Invasive Fungal Infections in Pediatric Patients. Pharmaceuticals 2022, 15, 375. https://doi.org/10.3390/ph15030375
Zimmermann P, Brethon B, Roupret-Serzec J, Caseris M, Goldwirt L, Baruchel A, de Tersant M. Isavuconazole Treatment for Invasive Fungal Infections in Pediatric Patients. Pharmaceuticals. 2022; 15(3):375. https://doi.org/10.3390/ph15030375
Chicago/Turabian StyleZimmermann, Philippe, Benoit Brethon, Julie Roupret-Serzec, Marion Caseris, Lauriane Goldwirt, André Baruchel, and Marie de Tersant. 2022. "Isavuconazole Treatment for Invasive Fungal Infections in Pediatric Patients" Pharmaceuticals 15, no. 3: 375. https://doi.org/10.3390/ph15030375
APA StyleZimmermann, P., Brethon, B., Roupret-Serzec, J., Caseris, M., Goldwirt, L., Baruchel, A., & de Tersant, M. (2022). Isavuconazole Treatment for Invasive Fungal Infections in Pediatric Patients. Pharmaceuticals, 15(3), 375. https://doi.org/10.3390/ph15030375