8
(0.57; 0.82)
Tenofovir disoproxil fumarate (TDF) 300 mg qd TDF for 7 days 750 mg q8h for 7 days 16 ↔ 1.01
(0.96; 1.05) 1.00
(0.94; 1.07) 1.03
(0.93; 1.14)
Tenofovir disoproxil fumarate (TDF) and efavirenz (EFV) 600 mg EFV /300 mg TDF qd for 7 days 1125 mg q8h for 7 days 15 ↓ 0.86§
(0.76; 0.97) 0.82§
(0.73; 0.92) 0.75§
(0.66; 0.86)
600 mg EFV /300 mg TDF qd for 7 days 1500 mg q12h for 7 days 16 ↓ 0.97§
(0.88; 1.06) 0.80‡ , §
(0.73; 0.88) 0.52§
(0.42; 0.64)
*Data provided are under fed conditions unless otherwise noted.
†The direction of the arrow (↑ = increase, ↓ = decrease, ↔ = no change) indicates the direction of the change in PK
‡Cavg,ss = Average concentrations at steady state (AUCτ/τ).
§Value with co-administered drug and telaprevir / value with telaprevir 750 mg q8h alone
Table 7 Drug Interactions: Summary of Pharmacokinetic Parameters for Co-administered Drugs in the Presence of Telaprevir Drug Dose and Schedule N Effect on Drug PK* LS Mean Ratio (90% CI) of Drug PK With/Without Telaprevir
Drug Telaprevir Cmax AUC Cmin
Alprazolam 0.5 mg single dose 750 mg q8h for 10 days 17 ↑ 0.97
(0.92; 1.03) 1.35
(1.23; 1.49) NA
Amlodipine 5 mg single dose 750 mg q8h for 7 days 19 ↑ 1.27
(1.21; 1.33) 2.79
(2.58; 3.01) NA
Atorvastatin 20 mg single dose 750 mg q8h for 7 days 19 ↑ 10.60
(8.74; 12.85) 7.88
(6.84; 9.07) NA
Cyclosporine A (CsA) 100 mg single dose when administered alone; 10 mg single dose when co-administered with telaprevir (D8) 750 mg q8h for 11 days 9 ↑ 0.13
(0.11; 0.16)
Dose norm.: 1.32
(1.08; 1.60) 0.46
(0.39; 0.55)
Dose norm.: 4.64
(3.90; 5.51) NA
Digoxin 2 mg single dose 750 mg q8h for 11 days 20 ↑ 1.50
(1.36; 1.65) 1.85
(1.70; 2.00) NA
Escitalopram 10 mg qd, for 7 days 750 mg q8h for 14 days
13 ↓ 0.70
(0.65; 0.76) 0.65
(0.60; 0.70) 0.58
(0.52; 0.64)
Ethinyl estradiol (EE), co-administered with norethindrone (NE) 0.035 mg qd EE/ 0.5 mg
qd NE for 21 days 750 mg q8h for 21 days 24 ↓ 0.74
(0.68; 0.80) 0.72
(0.69; 0.75) 0.67
(0.63; 0.71)
Ketoconazole 400 mg single dose 1250 mg q8h for 4 doses 81 ↑ 1.23
(1.14; 1.33) 1.46
(1.35; 1.58) NA
200 mg single dose 1250 mg q8h for 4 doses 28 ↑ 1.75
(1.51; 2.03) 2.25
(1.93; 2.61) NA
R-Methadone Methadone maintenance therapy (40 to 120 mg/daily) 750 mg q8h for 7 days 15 ↓ 0.71
(0.66; 0.76) 0.71
(0.66; 0.76) 0.69
(0.64; 0.75)
S-Methadone Methadone maintenance therapy (40 to 120 mg/daily) 750 mg q8h for 7 days 15 ↓ 0.65
(0.60; 0.71) 0.64
(0.58; 0.70) 0.60
(0.54; 0.67)
Midazolam (iv) 0.5 mg iv single dose 750 mg q8h for 9 days 22 ↑ 1.02
(0.8; 1.31) 3.40
(3.04; 3.79) NA
Midazolam (oral) 2 mg oral single dose 750 mg q8h for 11 days 21 ↑ 2.86
(2.52; 3.25) 8.96
(7.75; 10.35) NA
Norethindrone (NE), co-administered with EE 0.035 mg qd EE/ 0.5 mg
qd NE for 21 days 750 mg q8h for 7 days 24 ↔ 0.85
(0.81; 0.89) 0.89
(0.86; 0.93) 0.94
(0.87; 1.0)
Tacrolimus 2 mg single dose when administered alone; 0.5 mg single dose when co-administered with telaprevir (D8) 750 mg q8h for 13 days 9 ↑ 2.34
(1.68; 3.25)
Dose norm.: 9.35
(6.73; 13.0) 17.6
(13.2; 23.3)
Dose norm.: 70.3
(52.9; 93.4) NA
Zolpidem 5 mg single dose 750 mg q8h for 10 days 19 ↓ 0.58
(0. |
