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Isavuconazole: Need for therapeutic drug monitoring and CYP polymorphism testing

Summary

A patient with a serious fungal infection of the sinuses caused by Rhizopus arrhizus received the antifungal drug isavuconazole. However, blood tests showed the drug was building up to dangerously high levels in her body. Genetic testing revealed she had a mutation that made her body unable to break down the drug normally. The doctors had to give her much smaller and less frequent doses while carefully monitoring her drug levels to keep her safe.

Background

Isavuconazole is used for treatment of mucormycosis, an invasive fungal infection. Therapeutic drug monitoring (TDM) is not routinely recommended for isavuconazole, but high plasma concentrations are necessary for optimal penetration to infection sites.

Objective

To demonstrate the importance of therapeutic drug monitoring and CYP polymorphism genetic testing in a patient with mucormycosis caused by Rhizopus arrhizus who exhibited unusually high isavuconazole levels on standard dosing.

Results

The patient had an isavuconazole trough level of 88 mg/L on standard 200 mg/day dosing. Genotyping revealed CYP3A5*3/*3 polymorphism indicating poor drug metabolism. When dose was reduced to 100 mg/day, level decreased to 38 mg/L. Posaconazole as an alternative caused intractable vomiting, necessitating very low-frequency isavuconazole dosing.

Conclusion

This case highlights the clinical utility of therapeutic drug monitoring for isavuconazole and the potential need for CYP polymorphism genetic testing in patients with supra-therapeutic drug levels. Very low and infrequent dosing guided by TDM may be necessary in poor metabolizers.
  • Published in:Medical Mycology Case Reports,
  • Study Type:Case Report,
  • Source: PMID: 41079970, DOI: 10.1016/j.mmcr.2025.100736
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