abine. A population pharmacokinetic analysis comparing Caucasians and non-Caucasians (predominately African American and Hispanic patients) showed no significant pharmacokinetic difference. No adjustment of the ezogabine dose for race is recommended.
Gender: The impact of gender on the pharmacokinetics of ezogabine was examined following a single dose of POTIGA to healthy young (aged 21 to 40 years) and elderly (aged 66 to 82 years) subjects. The AUC values were approximately 20% higher in young females compared to young males and approximately 30% higher in elderly females compared to elderly males. The Cmax values were approximately 50% higher in young females compared to young males and approximately 100% higher in elderly females compared to elderly males. There was no gender difference in weight-normalized clearance. Overall, no adjustment of the dosage of POTIGA is recommended based on gender.
Pediatric Patients: The pharmacokinetics of ezogabine in pediatric patients have not been investigated.
Geriatric: The impact of age on the pharmacokinetics of ezogabine was examined following a single dose of ezogabine to healthy young (aged 21 to 40 years) and elderly (aged 66 to 82 years) subjects. Systemic exposure (AUC) of ezogabine was approximately 40% to 50% higher and terminal half-life was prolonged by approximately 30% in the elderly compared to the younger subjects. The peak concentration (Cmax) was similar to that observed in younger subjects. A dosage reduction in the elderly is recommended [see Dosage and Administration (2), Use in Specific Populations (8.5)].
Renal Impairment: The pharmacokinetics of ezogabine were studied following a single 100-mg dose of POTIGA in subjects with normal (CrCL >80 ml/min), mild (CrCL ≥50 to <80 mL/min), moderate (CrCL ≥30 to <50 mL/min), or severe renal impairment (CrCL <30 mL/min) (n = 6 in each cohort) and in subjects with ESRD requiring hemodialysis (n = 6). The ezogabine AUC was increased by approximately 30% in patients with mild renal impairment and doubled in patients with moderate impairment to ESRD (CrCL <50 mL/min) relative to healthy subjects. Similar increases in NAMR exposure were observed in the various degrees of renal impairment. The effect of hemodialysis on ezogabine clearance has not been established. Dosage reduction is recommended for patients with creatinine clearance <50 mL/min and for patients with ESRD receiving dialysis [see Dosage and Administration (2), Use in Specific Populations (8.6)].
Hepatic Impairment: The pharmacokinetics of ezogabine were studied following a single 100-mg dose of POTIGA in subjects with normal, mild (Child-Pugh score 5 to 6), moderate (Child-Pugh score 7 to 9), or severe hepatic (Child-Pugh score >9) impairment (n = 6 in each cohort). Relative to healthy subjects, ezogabine AUC was not affected by mild hepatic impairment, but was increased by approximately 50% in subjects with moderate hepatic impairment and doubled in subjects with severe hepatic impairment. There was an increase of approximately 30% in exposure to NAMR in patients with moderate to severe impairment. Dosage reduction is recommended for patients with moderate and severe hepatic impairment [see Dosage and Administration (2), Use in Specific Populations (8.7)].
Drug Interactions:In vitro studies using human liver microsomes indicated that ezogabine does not inhibit enzyme activity for CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4/5. Inhib |
