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VIEKIRA XR(dasabuvir, ombitasvir, paritaprevir, and ritonavir)extended-release tablets(十九)
ion biliary excretion metabolism metabolism metabolism
t1/2 (hr)f 21-25 5.5 4 5.5-6
% of dose excreted in fecesg 90.2 88 86.4 94.4
% of dose excreted unchanged in fecesg 87.8 1.1 33.8 26.2
% of dose excreted in urineg 1.91 8.8 11.3 ~ 2
% of dose excreted unchanged in urineg 0.03 0.05 3.5 0.03
NA - data not available
High fat meal of 753 Kcal; 55.3% calories from fat, 27.8% calories from carbohydrates, and 16.9% calories from protein.
Similar results are expected for ombitasvir, paritaprevir and dasabuvir under moderate fat meal conditions.
Steady state exposures are achieved after approximately 12 days of dosing.
It is apparent volume of distribution (V/F) for ritonavir.
Ombitasvir, paritaprevir, ritonavir, and dasabuvir do not inhibit organic anion transporter (OAT1) in vivo and based on in vitro data, are not expected to inhibit organic cation transporter (OCT2), organic anion transporter (OAT3), or multidrug and toxin extrusion proteins (MATE1 and MATE2K) at clinically relevant concentrations.
t1/2 values refer to the mean elimination half-life.
Dosing in mass balance studies: single dose administration of [14C] ombitasvir; single dose administration of [14C] paritaprevir co-dosed with 100 mg ritonavir; single dose administration of [14C] dasabuvir.
Specific Populations
There are no clinically relevant changes in the pharmacokinetics of the components of VIEKIRA XR in relation to sex, race/ethnicity, or geriatric age [see Use in Specific Populations (8.5)]. The pharmacokinetics of VIEKIRA XR in pediatric patients less than 18 years of age have not been established [see Use in Specific Populations (8.4)].
Hepatic Impairment
The single dose pharmacokinetics of the combination of dasabuvir, ombitasvir, paritaprevir, and ritonavir were eva luated in non-HCV infected subjects with mild hepatic impairment (Child-Pugh Category A; score of 5-6), moderate hepatic impairment (Child-Pugh Category B, score of 7-9) and severe hepatic impairment (Child-Pugh Category C, score of 10-15).
Relative to subjects with normal hepatic function, dasabuvir AUC values increased by 17%, and ombitasvir, paritaprevir and ritonavir AUC values decreased by 8%, 29% and 34%, respectively, in subjects with mild hepatic impairment.
Relative to subjects with normal hepatic function, dasabuvir, ombitasvir, and ritonavir AUC values decreased by 16%, 30%, and 30% respectively, and paritaprevir AUC values increased by 62% in subjects with moderate hepatic impairment.
Relative to subjects with normal hepatic function, dasabuvir, paritaprevir, and ritonavir AUC values increased by 325%, 945%, and 13%, respectively, and ombitasvir AUC values decreased by 54% in subjects with severe hepatic impairment.
Renal Impairment
The single dose pharmacokinetics of the combination of dasabuvir, ombitasvir, paritaprevir, and ritonavir were eva luated in non-HCV infected subjects with mild (CLcr: 60 to 89 mL/min), moderate (CLcr: 30 to 59 mL/min), and severe (CLcr: 15 to 29 mL/min) renal impairment.
Pharmacokinetic data are not available on the use of VIEKIRA XR in non-HCV infected subjects with End Stage Renal Disease (ESRD).
Relative to subjects with normal renal function, dasabuvir, paritaprevir, and ritonavir AUC values increased by 21%, 19%, and 42% respect |
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