Impact of patient education on plasma concentrations and effectiveness of posaconazole oral suspension under clinical conditions

Abstract

Posaconazole prophylaxis is recommended for patients with acute myeloid leukaemia during induction chemotherapy. Although a tablet formulation with better oral bioavailability is available, some patients have to rely on the oral suspension in clinical routine. Therefore, effectiveness of posaconazole oral suspension under real-life clinical conditions and impact of patient education about the correct intake on its plasma concentrations were assessed in this study. Altogether 96 patients receiving 160 cycles of induction chemotherapy were retrospectively (40 patients) and prospectively (56 patients) analysed. Patients were assigned into two groups for each chemotherapy cycle according to the application of antifungal prophylaxis (A: posaconazole oral suspension, 200 mg three times a day ≥7 days; B: intake <7 days, fluconazole or no prophylaxis). Antifungal prophylaxis and therapy were analysed for each cycle. Additionally, plasma concentrations were determined from prospectively included subjects of group A who were intensively educated to perform a correct drug intake. Systemic antifungal therapy was statistically started less often in group A (26% vs 53%; P = 0.002). Posaconazole prophylaxis was associated with a lower risk of proven invasive fungal infection (P = 0.003). Median plasma concentration apparently increased between the first and second time of determination effected by an initial intensive on-site patient education. The clinical effectiveness of posaconazole oral suspension was confirmed. A detailed patient education at the beginning of the treatment with posaconazole oral suspensions seems to be of primary importance for efficient plasma concentrations.

Posaconazole treatment of refractory coccidioidomycosis in dogs

“…The reports in the literature of dogs treated with posaconazole generally lack measurement of serum drug concentrations. Posaconazole is lipophilic and poorly soluble, and the commercial suspension has low bioavailability in humans, requiring daily doses of 800 mg to achieve therapeutic blood drug concentrations (~0.5‐1 μg/mL) 22‐24 . Posaconazole delayed release (DR) tablets have greatly improved bioavailability for humans, 21 and bioavailability and half‐life appear to be similarly greater in dogs receiving DR tablets compared to the commercial suspension 23 .…”

“…Posaconazole is lipophilic and poorly soluble, and the commercial suspension has low bioavailability in humans, requiring daily doses of 800 mg to achieve therapeutic blood drug concentrations (~0.5‐1 μg/mL). 22 , 23 , 24 Posaconazole delayed release (DR) tablets have greatly improved bioavailability for humans, 21 and bioavailability and half‐life appear to be similarly greater in dogs receiving DR tablets compared to the commercial suspension. 23 Two German shepherd dogs with disseminated aspergillosis receiving posaconazole suspension 5 mg/kg q12 h had serum concentrations over 3 μg/mL, though the time of collection relative to drug administration was not reported.…”

“… 22 , 23 , 24 Posaconazole delayed release (DR) tablets have greatly improved bioavailability for humans, 21 and bioavailability and half‐life appear to be similarly greater in dogs receiving DR tablets compared to the commercial suspension. 23 Two German shepherd dogs with disseminated aspergillosis receiving posaconazole suspension 5 mg/kg q12 h had serum concentrations over 3 μg/mL, though the time of collection relative to drug administration was not reported. 15 In that study, 1 of the dogs responded and 1 did not respond to treatment.…”

Antifungal Drugs TDM: Trends and Update

“…However, PSZ tablets, which are widely used and unlikely to result in underexposure, may not justify routine TDM. 168,169,234,235,236,[238][239][240][241][244][245][246] Blood Trough 261,262,268,[281][282][283][284]314,315,320,323,327,330,331,333,340 Concentrations Targets 341,344,347,350,352,353,355,[358][359][360][361] and TDM Indications 364,522,[526][527][528][529][530][531][532][533][534][535][536]…”

“…A median exposure of 0.8 mg/L can be achieved with 200 mg •3 and can be improved by therapeutic patient education. 327…”