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VIEKIRA XR(dasabuvir, ombitasvir, paritaprevir, and ritonavir)extended-release tablets(二十四)
stered with the components of VIEKIRA XR in the test arm and 2 mg sirolimus was administered in the reference arm without the components of VIEKIRA XR.
NA: not available/not applicable; DAA: Direct-acting antiviral agent; CI: Confidence interval
Doses of dasabuvir were 250 mg or 400 mg (both doses showed similar exposures). Doses of ombitasvir, paritaprevir, and ritonavir were 25 mg, 150 mg and 100 mg.
Dasabuvir was dosed twice daily and ombitasvir, paritaprevir and ritonavir were dosed once daily in all the above studies except studies with gemfibrozil, ketoconazole and carbamazepine that used single doses.
TABLE 8 summarizes the effects of dasabuvir, ombitasvir, paritaprevir, and ritonavir on the pharmacokinetics of co-administered drugs which showed clinically relevant changes. For information regarding clinical recommendations, see Drug Interactions (7).
Table 8. Drug Interactions: Change in Pharmacokinetic Parameters for Co-administered Drug in the Presence of VIEKIRA XR
Co-administered
Drug Dose of Co-
administered
Drug (mg) n Ratio (with/without the Components
of VIEKIRA XR) of Co-administered
Drug Pharmacokinetic Parameters
(90% CI); No Effect = 1.00
Cmax AUC Cmin
Alprazolam 0.5 single dose 12 1.09
(1.03, 1.15) 1.34
(1.15, 1.55) NA
Amlodipine 5 single dose 14 1.26
(1.11, 1.44) 2.57
(2.31, 2.86) NA
Atazanavir/
ritonavira Atazanavir 300
and ritonavir
100 once daily
in the evening 12 1.02
(0.92, 1.13)b 1.19
(1.11, 1.28)b 1.68
(1.44, 1.95)b
Buprenorphine Buprenorphine:
4 to 24 once
daily and
Naloxone 1 to
6 once daily 10 2.18
(1.78, 2.68)c 2.07
(1.78, 2.40)c 3.12
(2.29, 4.27)c
Norbuprenorphine 2.07
(1.42, 3.01)c 1.84
(1.30, 2.60)c 2.10
(1.49, 2.97)c
Naloxone 1.18
(0.81, 1.73) 1.28
(0.92, 1.79)c NA
Carbamazepine 200 once daily
followed by
200 twice daily 12 1.10
(1.07, 1.14) 1.17
(1.13, 1.22) 1.35
(1.27, 1.45)
Carbamazepine’s
metabolite,
carbamazepine-
10,11-epoxide
(CBZE) 0.84
(0.82, 0.87) 0.75
(0.73, 0.77) 0.57
(0.54, 0.61)
Carisoprodol 250 single dose 14 0.54
(0.47, 0.63) 0.62
(0.55, 0.70) NA
Carisoprodol's
metabolite,
mepobramate 1.17
(1.10, 1.25) 1.09
(1.03, 1.16) NA
Cyclobenzaprine 5 single dose 14 0.68
(0.61, 0.75) 0.60
(0.53, 0.68) NA
Cyclobenzaprine's
metabolite,
norcyclobenzaprine 1.03
(0.87, 1.23) 0.74
(0.64, 0.85) NA
Cyclosporine 30 single dosed 10 1.01
(0.85, 1.20)c 5.82
(4.73, 7.14)c 15.80
(13.81, 18.09)c
Darunavire 800 once daily 8 0.92
(0.87, 0.98)b 0.76
(0.71, 0.82)b 0.52
(0.47, 0.58)b
Darunavir/
ritonavirf Darunavir 600
twice daily and
ritonavir 100
once daily in
the evening 7 0.87
(0.79, 0.96)b 0.80
(0.74, 0.86)b 0.57
(0.48, 0.67)b
Darunavir/
ritonavirg Darunavir 800
and ritonavir
100 once dai |
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