Table 4.
Main studies reporting the experience with TDM of isavuconazole.
| References | Patients’ Underlying Condition (Number) | Total No. of Patients | No. of Measurements | Mean/Median, mg/L |
Min–Max, mg/L |
Subtherapeutic Levels (<1 mg/L) |
Potentially Supratherapeutic Levels | Safety: No. of Patients with Side Effects | Comment |
|---|---|---|---|---|---|---|---|---|---|
| Furfaro et al., 2019 [76] | HM (13); other (6) | 19 | 264 | Median 3.6; median 2.86 during the first 14 days; median 4.4 after 14 days of therapy |
0.64–8.13 | ND | ND | 6 (31.6%) gastrointestinal | Failure in 1 with concentration of 1.55 GI side effects were associated with high levels (5.13 mg/L) and prolonged administration Drug accumulation observed over time |
| Kosmidis et al., 2020 [79] | Chronic pulmonary aspergillosis | 45 | 285 | Overall mean 4.1; mean 4.6 if dose 200 mg/day; mean 4.1 if 200 mg/100 mg on alternate days; mean 3.7 if 100 mg/day |
1.1–10.1 | <1 mg/L in none of the patients All 117 measurements from patients taking 100 mg/day were >1 mg/L |
>6 mg/L in 36 (13%) | 16 (36%) discounted ISA due to side effects (5 within 28 days) such as hepatotoxicity in 4, neuropathy in 3, headache in 2, malaise in 2, weight loss in 1, confusion in 1, nausea in 1, photosensitivity in 1 case, dysgeusia in 1 | 38 patients (86%) were started on a standard dose ISA at lower dose resulted in acceptable levels and favorable profile during > 6 months of therapy |
| Borman et al., 2020 [75] | ND | 150 | 210 | Mean 3.32 | 0.5–11.6 | <1 mg/L in 6 (4%), patients 62 (41%) achieved target level of 2–4 mg/L |
ND | ND | In patients <18 years greater interpatient variability of blood levels was found |
| Zurl et al., 2020 [81] | HM (14), SOT (4), cancer (2), other (12), including osteomyelitis | 33 | 140 | Median 2.35 If RRT/ECMO excluded: median 3.05 |
0.66–9.1 1.38–9.1 |
Only in case of RRT, ECMO, or Cytosorb use | ND | 6 (18%) developed side effects: 1 anaphylaxis, 1 leukopenia, 2 increased liver enzymes, 1 paraesthesia, 1 erythema, and elevated liver enzymes | Lower concentration in case of RRT (median 0.91 in 7 patients), ECMO, and Cytosorb® |
| McCreary et al., 2020 [82] | SOT (18), HSCT (1) treated with ISA via enteral feeding tube | 19 | ND | Mean 1.8 | 0.3–5.2 | <1 mg/L in 2 | >5 mg/L in 1 | ND | Favorable PK confirms that capsule content can be safely sprinkled into an enteral feeding tube |
| Risum et al., 2021 [80] | HM (16); SOT (2); pulmonary disorder (13); (COPD in 7); other (5) | 36 | 273 | Median 4.3 | 0.5–15.4 | <0.2 mg/L in 7 (no data on compliance) 32/273 (12%) measurements <2 mg/L |
>10 mg/L in 9/247 (4%) | ND | One case of ISA detectable for 35 days after stopping |
| Kronig et al., 2021 [77] | All HM or HSCT | 16 | 35 | Mean 2.9 | 0.9–6.7 | ND | ND | Discontinued in 5 (16%): hypersensitivity in 2, increased liver enzymes in 2, drug interactions in 1 | |
| Cojutti et al., 2021 [78] | Onco-hematological malignancy (25); other (25) | 50 | 199 | Median 3.68 | 2.07–5.38 | ND | ND | ND | Drug accumulation observed over time In Monte Carlo simulations standard dose was optimal against A. fumigatus and A. flavus with MIC up to 1 mg/L |
Abbreviations: ECMO, extracorporeal membrane oxygenation; GI, gastrointestinal; HM, hematological malignancies; HSCT, hematopoietic stem cell transplantation; ISA, isavuconazole; MIC, minimum inhibitory concentrations; ND, no data; PK, pharmacokinetics; RRT, renal replacement therapy; SOT, solid organ transplant.