TY - JOUR
T1 - Therapeutic drug monitoring of isavuconazole
T2 - Serum concentration variability and success rates for reaching target in comparison with voriconazole
AU - Risum, Malene
AU - Vestergaard, Mai-Britt
AU - Weinreich, Ulla Møller
AU - Helleberg, Marie
AU - Vissing, Nadja Hawwa
AU - Jørgensen, René
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
KW - Antifungal drug
KW - Aspergillosis
KW - Mucormycosis
KW - Therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=85105270081&partnerID=8YFLogxK
U2 - 10.3390/antibiotics10050487
DO - 10.3390/antibiotics10050487
M3 - Journal article
C2 - 33922419
AN - SCOPUS:85105270081
SN - 2079-6382
VL - 10
JO - Antibiotics
JF - Antibiotics
IS - 5
M1 - 487
ER -