Interactions: Summary of Pharmacokinetic Parameters for Telaprevir in the Presence of Co-administered Drugs* Drug Dose and Schedule N Effect on Telaprevir PK† LS Mean Ratio (90% CI) of Telaprevir PK With/Without Co-administered Drug
Drug Telaprevir Cmax AUC or Cavg,ss‡ Cmin
NA: not available/ not applicable; N = Number of subjects with data; qd = once daily; bid = twice daily; q8h = every 8 hours; q12h = every 12 hours
*
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
Escitalopram 10 mg qd for 7 days 750 mg q8h for 14 days 13 ↔ 1.00
(0.95; 1.05) 0.93
(0.89; 0.97) 0.91
(0.86; 0.97)
Esomeprazole 40 mg qd for 6 days 750 mg single dose 24 ↔ 0.95
(0.86; 1.06) 0.98
(0.91; 1.05) NA
Ketoconazole Ketoconazole
400 mg single dose 750 mg single dose 17 ↑ 1.24
(1.10; 1.41) 1.62
(1.45; 1.81) NA
Oral Contraceptive Norethindrone/ ethinyl estradiol 0.5 mg/0.035 mg qd for 21 days 750 mg q8h for 21 days 23 ↔ 1.00
(0.93; 1.07) 0.99
(0.93; 1.05) 1.00
(0.93; 1.08)
Rifampin 600 mg qd for 8 days 750 mg single dose 16 ↓ 0.14
(0.11; 0.18) 0.08
(0.07; 0.11) NA
Anti-HIV Drugs
Atazanavir (ATV)/ritonavir (rtv) 300 mg ATV/ 100 mg rtv qd for 20 days 750 mg q8h for 10 days 14 ↓ 0.79
(0.74; 0.84) 0.80
(0.76; 0.85) 0.85
(0.75; 0.98)
Darunavir (DRV)/ritonavir (rtv) 600 mg DRV/ 100 mg rtv bid for 20 days 750 mg q8h for 10 days 11 (N=14 for Cmax) ↓ 0.64
(0.61; 0.67) 0.65
(0.61; 0.69) 0.68
(0.63; 0.74)
Efavirenz 600 mg qd for 20 days 750 mg q8h for 10 days 21 ↓ 0.91
(0.82; 1.02) 0.74
(0.65; 0.84) 0.53
(0.44; 0.65)
Fosamprenavir (fAPV)/ ritonavir (rtv) 700 mg fAPV/ 100 mg rtv bid for 20 days 750 mg q8h for 10 days 18 ↓ 0.67
(0.63; 0.71) 0.68
(0.63; 0.72) 0.70
(0.64; 0.77)
Lopinavir (LPV)/ritonavir (rtv) 400 mg LPV/ 100 mg rtv bid for 20 days 750 mg q8h for 10 days 12 ↓ 0.47
(0.41; 0.52) 0.46
(0.41; 0.52) 0.48
(0.40; 0.56)
Ritonavir 100 mg single dose 750 mg single dose 14 ↑ 1.30
(1.15; 1.47) 2.00
(1.72; 2.33) NA
Ritonavir 100 mg q12h for 14 days 750 mg q12h for 14 days 5 ↓ 0.85
(0.63; 1.13) 0.76‡,§
(0.60; 0.97) 0.68
(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)
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
*
The direction of the arrow (↑ = increase, ↓ = decrease, ↔ = no change) indicates the direction of the change in PK
Alprazolam 0.5 mg single dose 750 mg |
