s of age) and adults (≥18 years of age). This is consistent with pharmacokinetic data from another study in which mean steady-state posaconazole Cav from 12 adolescent patients (8-17 years of age) was similar to that in the adults (≥18 years of age).
8.5 Geriatric Use
Of the 230 patients treated with posaconazole delayed-release tablets, 38 (17%) were greater than 65 years of age. The pharmacokinetics of posaconazole delayed-release tablets are comparable in young and elderly subjects. No overall differences in safety were observed between the geriatric patients and younger patients; therefore, no dosage adjustment is recommended for geriatric patients.
Of the 605 patients randomized to posaconazole oral suspension in the prophylaxis clinical trials, 63 (10%) were ≥65 years of age. In addition, 48 patients treated with greater than or equal to 800-mg/day posaconazole in another indication were ≥65 years of age. No overall differences in safety were observed between the geriatric patients and younger patients; therefore, no dosage adjustment is recommended for geriatric patients. The pharmacokinetics of posaconazole oral suspension are comparable in young and elderly subjects (≥65 years of age). No adjustment in the dosage of Noxafil is necessary in elderly patients (≥65 years of age) based on age. No overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out.
8.6 Renal Impairment
Following single-dose administration of 400 mg of the oral suspension, there was no significant effect of mild (CLcr: 50-80 mL/min/1.73 m2, n=6) or moderate (CLcr: 20-49 mL/min/1.73 m2, n=6) renal impairment on posaconazole pharmacokinetics; therefore, no dose adjustment is required in patients with mild to moderate renal impairment. In subjects with severe renal impairment (CLcr: <20 mL/min/1.73 m2), the mean plasma exposure (AUC) was similar to that in patients with normal renal function (CLcr: >80 mL/min/1.73 m2); however, the range of the AUC estimates was highly variable (CV=96%) in these subjects with severe renal impairment as compared to that in the other renal impairment groups (CV<40%). Due to the variability in exposure, patients with severe renal impairment should be monitored closely for breakthrough fungal infections [see Dosage and Administration (2)]. Similar recommendations apply to posaconazole delayed-release tablets; however, a specific study has not been conducted with the delayed-release tablets.
8.7 Hepatic Impairment
After a single oral dose of posaconazole oral suspension 400 mg, the mean AUC was 43%, 27%, and 21% higher in subjects with mild (Child-Pugh Class A, N=6), moderate (Child-Pugh Class B, N=6), or severe (Child-Pugh Class C, N=6) hepatic impairment, respectively, compared to subjects with normal hepatic function (N=18). Compared to subjects with normal hepatic function, the mean Cmax was 1% higher, 40% higher, and 34% lower in subjects with mild, moderate, or severe hepatic impairment, respectively. The mean apparent oral clearance (CL/F) was reduced by 18%, 36%, and 28% in subjects with mild, moderate, or severe hepatic impairment, respectively, compared to subjects with normal hepatic function. The elimination half-life (t½) was 27 hours, 39 hours, 27 hours, and 43 hours in subjects with normal hepatic fu
