Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

Antibiotics (Basel). 2021 Apr 23;10(5):487. doi: 10.3390/antibiotics10050487.


Isavuconazole (ISZ) is used in the treatment of aspergillosis and mucormycosis. The purpose of this study was to evaluate the therapeutic drug monitoring (TDM) of ISZ samples from a clinical setting performed at Statens Serum Institut. Materials/methods: Isavuconazole serum concentrations were determined by fluorescent detection on a UHPLC. Serum-ISZ (s-ISZ) results were included and compared to those of serum-voriconazole (s-VRZ) in a 33 month period from March 2017. Clinical data were obtained for patients receiving ISZ. The therapeutic range was initially 2-10 mg/L, but was adjusted to 2-5 mg/L during the study period except for selected patients with Mucorales infections who received off-label doses of ISZ. Results: A total of 273 s-ISZ and 1242 s-VRZ measurements from 35 and 283 patients, respectively, were included. Seventeen patients had received both ISZ and VRZ with TDM within the study period. The median s-ISZ was 4.3 mg/L (0.5-15.4 mg/L) with 83% of measurements within the therapeutic index. The median s-VRZ was 2.6 mg/L (0.2-21.9 mg/L) with 67% of measurements within the therapeutic index. The median intra-/interindividual coefficient of variation (CV) was 43.4%/54.8% for ISZ compared to 53.2%/83.3% for VRZ. For patients receiving ISZ, the adverse events were mostly gastroenteric and few drug-drug interactions were observed. Furthermore, immediate change from ISZ to VRZ treatment seemed to lead to prolonged metabolism of ISZ with detection up to 35 days after discontinuation. Conclusions: The majority of patients achieved s-ISZ levels well within the therapeutic range with less intra/interindividual CV than patients receiving VRZ.

PMID:33922419 | DOI:10.3390/antibiotics10050487