hibit OAT1 and is not expected to inhibit OCT2, OAT3, MATE1 and MATE2K at clinically relevant concentrations.
Special populations
Elderly
Based on population pharmacokinetic analysis of data from Phase 3 clinical studies, a 10 year increase or decrease in age from 54 years (median age in the Phase 3 studies) would result in approximately 10% change in ombitasvir exposures, and ≤20% change in paritaprevir exposures. There is no pharmacokinetic information in patients >75 years.
Sex or body weight
Based on population pharmacokinetic analysis of data from Phase 3 clinical studies, female subjects would have approximately 55% higher, 100% higher and 15% higher ombitasvir, paritaprevir and ritonavir exposures than male subjects. However, no dose-adjustment based on gender is warranted. A 10 kg change in body weight from 76 kg (median weight in the Phase 3 studies) would results in <10% change in ombitasvir exposures, and no change in paritaprevir exposures. Body weight is not a significant predictor of ritonavir exposures.
Race or ethnicity
Based on population pharmacokinetic analysis of data from Phase 3 clinical studies, Asian subjects had 18% to 21% higher ombitasvir exposures, and 37% to 39% higher paritaprevir exposures than non-Asian subjects. The ritonavir exposures were comparable between Asians and non-Asians.
Renal impairment
The changes in ombitasvir, paritaprevir, and ritonavir exposures in subjects with mild, moderate and severe renal impairment are not considered to be clinically significant. No dose adjustment for Viekirax with and without dasabuvir is recommended in HCV-infected patients with mild, moderate or severe renal impairment (see section 4.2). Viekirax has not been studied in HCV-infected patients on dialysis.
Pharmacokinetics of the combination of ombitasvir 25 mg, paritaprevir 150 mg, and ritonavir 100 mg, with or without dasabuvir 400 mg were eva luated in subjects with mild (CrCl: 60 to 89 ml/min), moderate (CrCl: 30 to 59 ml/min) and severe (CrCl: 15 to 29 ml/min) renal impairment.
Following administration of Viekirax and dasabuvir
Compared to the subjects with normal renal function, ombitasvir exposures were comparable in subjects with mild, moderate and severe renal impairment. Compared to the subjects with normal renal function, paritaprevir Cmax values were comparable, but AUC values were 19%, 33% and 45% higher in mild, moderate and severe renal impairment, respectively. Ritonavir plasma concentrations increased when renal function was reduced: Cmax and AUC values were 26% to 42% higher, 48% to 80% higher and 66% to 114% higher in subjects with mild, moderate and severe renal impairment, respectively.
Following administration of Viekirax
Following administration of Viekirax, the changes in ombitasvir, paritaprevir, and ritonavir exposures in subjects with mild, moderate and severe renal impairment were similar to those observed when Viekirax was administered with dasabuvir, and are not considered to be clinically significant.
Hepatic impairment
The changes in ombitasvir, paritaprevir, and ritonavir exposures in subjects with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment are not considered clinically significant. No dose adjustment for Viekirax or dasabuvir is recommended in HCV-infected patients with mild and moderate hepatic impairment (see section 4.2).
F
