Table 1.
Baseline characteristics and posaconazole concentrations.
| Concentration 3000–4999 ng/mL (n = 80) | Concentration ≥5000 ng/mL (n = 10) | Total cohort (n = 90) | P-value | |
|---|---|---|---|---|
| Median [IQR] or n (%) | ||||
| Age (years), median, [IQR] | 62 [56–67] | 50 [34–55] | 61 [54–67] | 0.015 |
| Gender | 0.50 | |||
| Male | 37 (46.3%) | 3 (30%) | 40 (44.4%) | |
| Female | 43 (53.8%) | 7 (70%) | 50 (55.6%) | |
| Race | 0.58 | |||
| White | 73 (91.3%) | 9 (90%) | 82 (91.1%) | |
| Black | 1 (1.3%) | 0 (0%) | 1 (1.1%) | |
| Asian | 2 (2.5%) | 0 (0%) | 2 (2.2%) | |
| Other/missing | 4 (5%) | 1 (10%) | 5 (5.6%) | |
| Height (cm), median, [IQR] | 170 [165–177] | 155 [153–176] | 170 [163–177] | 0.057 |
| Weight (kg) median, [IQR] | 73 [59–87] | 53 [49–69] | 69 [57–85] | 0.007 |
| BMI, median, [IQR] | 25.0 [21.6–29.3] | 20.7 [19.7–23.5] | 24.5 [20.7–28.6] | 0.032 |
| Solid organ transplant | 23 (28.8%) | 1 (10%) | 24 (26.7%) | 0.28 |
| Hematopoietic stem cell transplant | 22 (27.5%) | 4 (40%) | 26 (28.9%) | 0.47 |
| Active malignancy | 23 (28.8%) | 3 (30%) | 26 (28.9%) | 0.99 |
| Other immunocompromised state | 4 (5.0%) | 1 (10%) | 5 (5.6%) | 0.45 |
| Cirrhosis | 1 (1.3%) | 0 (0%) | 1 (1.1%) | 0.99 |
| Systemic hypertension | 30 (37.5%) | 2 (20%) | 32 (35.6%) | 0.48 |
| Indication | 0.78 | |||
| Prophylaxis | 34 (42.5%) | 4 (40%) | 38 (42.2%) | |
| Empiric/culture negative | 7 (8.8%) | 0 (0%) | 7 (7.8%) | |
| Treatment | 39 (48.8%) | 6 (60%) | 45 (50%) | |
| Formulation | 0.30 | |||
| Delayed release tablet | 78 (97.5%) | 9 (90%) | 87 (96.7%) | |
| Liquid | 1 (1.3%) | 0 (0%) | 1 (1.1%) | |
| IV | 1 (1.3%) | 1 (10%) | 2 (2.2%) | |
| Supratherapeutic level (ng/mL), median, [IQR] | 3580 [3150–3960] | 6140 [5540–7040] | 3660 [3210–4310] | <0.001 |
| Time from initiation (days), median, (IQR] | 91 [26–443] | 27 [12–45] | 80 [22–411] | 0.066 |
| Loading dose (mg) | 22 (28.2%) | 2 (20%) | 24 (27.3%) | 0.72 |
| Initial dose (mg), median, [IQR] | 300 [300–300] | 300 [300–300] | 300 [300–300] | 0.23 |
| Current dose (mg), median, (range) | 300 (200–800) | 300 (200–600) | 300 (200–800) | 0.43 |
| Concentration prior to supratherapeutic draw | 41 (52.6%) | 4 (44.4%) | 45 (51.7%) | 0.73 |
| Prior concentration (ng/mL), median, [IQR] | 2080 [1410–2400] | 2360 [1528–4440] | 2080 [1410–2440] | 0.45 |
| Symptomatic at supratherapeutic concentration | 47 (58.8%) | 8 (80%) | 55 (61.1%) | 0.31 |
| Neurologic symptoms | 21 (44.7%) | 6 (75%) | 27 (49.1%) | 0.14 |
| Gastrointestinal symptoms | 15 (31.9%) | 3 (37.5%) | 18 (32.7%) | 0.99 |
| Cardiac symptoms | 13 (27.7%) | 2 (25%) | 15 (27.3%) | 0.99 |
| Respiratory symptoms | 14 (29.8%) | 1 (12.5%) | 15 (27.3%) | 0.42 |
| Other symptoms | 18 (38.3%) | 2 (25%) | 20 (36.4%) | 0.70 |
| Suspect possible hepatotoxicityb | 18 (23.4%) | 4 (40.0%) | 22 (25.3%) | 0.26 |
| Intervention | 0.94 | |||
| Decrease dose | 27 (33.8%) | 3 (30%) | 30 (33.3%) | |
| Discontinue antifungal | 9 (11.3%) | 1 (10%) | 10 (11.1%) | |
| Continue without change | 39 (48.8%) | 6 (60%) | 45 (50%) | |
| Other medication changec | 5 (6.3%) | 0 (0%) | 5 (5.6%) | |
| Next concentration (ng/mL), median, [IQR] | 2760 [1880–3910] | 2245 [823–3835] | 2760 [1740–3910] | 0.43 |
| Dose at next concentration (mg), median, [IQR] | 300 [200–300] | 300 [200–300] | 300 [200–300] | 0.87 |
a
Inherited immunodeficiency, use of immunosuppressant medications (adalimumab and mycophenolate), uncontrolled type 2 diabetes, and untreated Gleason 6 adenocarcinoma of the prostate.
b
Cholestatic injury pattern for the majority (82%, n = 18; 2 excluded, 2 unlikely, 11 possible, 2 probable, and 2 highly probable), followed by mixed (14%, n = 3; 1 unlikely and, 1 probable, 1 possible), and hepatocellular (5%, n = 1; 1 highly likely).
c
Posaconazole formulation change, held and then later re-initiated, or dose change occurring prior to obtaining concentration due to other laboratory abnormalities.
IQR, interquartile range; BMI, body mass index.