Isavuconazole
From IDWiki
Background
Mechanism of Action
- Azole antifungal that inhibits lanosterol 14-α demethylase in the peptidoglycan synthesis pathway
Spectrum of Activity
- Active against Candida, Cryptococcus, Aspergillus including Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger, and Mucorales
- Indications include Chromoblastomycosis, Cladophialophora, Coccidioides immitis
Breakpoints
| Species | ECOFF (mg/L) | Breakpoints (μg/mL) | ||
|---|---|---|---|---|
| S | ATU | R | ||
| Candida albicans | ||||
| Candida glabrata | ||||
| Candida krusei | ||||
| Candida parapsilosis | ||||
| Candida tropicalis | ||||
| Cryptococcus neoformans | ||||
| Cryptococcus gattii | ||||
| Aspergillus flavus | 2 | ≤1 | 2 | >2 |
| Aspergillus fumigatus | 2 | ≤1 | 2 | >2 |
| Aspergillus nidulans | 0.25 | ≤0.25 | — | >0.25 |
| Aspergillus niger | 4 | — | — | — |
| Aspergillus terreus | 1 | ≤1 | — | >2 |
Dosing
- Isavuconazole 200 mg IV tid for 6 doses followed by 200 mg IV daily
Renal Dosing
- No adjustment needed
Hepatic Dosing
- No adjustment needed
Safety
Adverse Drug Reactions
- Nausea, vomiting, diarrhea
- Elevated liver enzymes
- Generally transient ALT elevation that does not require change in therapy
- May also include severe cholestatic or hepatocellular enzyme rises within the first few months of therapy
- See also LiverTox
- Hypokalemia
Drug-Drug Interactions
- Increases levels of sirolimus and tacrolimus
- Increases levels of cyclosporine
- Contraindicated with carbamazepine
References
- ^ Annie Lee, Brendan Prideaux, Min Hee Lee, Matthew Zimmerman, Enriko Dolgov, David S. Perlin, Yanan Zhao. Tissue Distribution and Penetration of Isavuconazole at the Site of Infection in Experimental Invasive Aspergillosis in Mice with Underlying Chronic Granulomatous Disease. Antimicrobial Agents and Chemotherapy. 2019;63(6). doi:10.1128/aac.00524-19.
- ^ Felix Bergmann, Michael Wölfl-Duchek, Anselm Jorda, Valentin Al Jalali, Amelie Leutzendorff, Maria Sanz-Codina, Daniela Gompelmann, Karin Trimmel, Maria Weber, Sabine Eberl, Wisse Van Os, Iris K Minichmayr, Birgit Reiter, Thomas Stimpfl, Marco Idzko, Markus Zeitlinger. Pharmacokinetics of isavuconazole at different target sites in healthy volunteers after single and multiple intravenous infusions. Journal of Antimicrobial Chemotherapy. 2024;79(5):1169-1175. doi:10.1093/jac/dkae088.
- ^ Matthew R Davis, Sandy Chang, Pryce Gaynor, Erin K McCreary, Paul Allyn. Isavuconazole for treatment of refractory coccidioidal meningitis with concomitant cerebrospinal fluid and plasma therapeutic drug monitoring. Medical Mycology. 2021;59(9):939-942. doi:10.1093/mmy/myab035.
- ^ Claire Rouzaud, Vincent Jullien, Anne Herbrecht, Bruno Palmier, Simona Lapusan, Marjolaine Morgand, Romain Guéry, Amélie Dureault, François Danion, Stéphanie Puget, Lauriane Goldwirt, Fanny Lanternier, Olivier Lortholary. Isavuconazole Diffusion in Infected Human Brain. Antimicrobial Agents and Chemotherapy. 2019;63(10). doi:10.1128/aac.02474-18.
