Renal Impairment

After administration of a single dose of 750 mg to HCV-negative subjects with severe renal impairment (CrCl less than 30 mL/min), the LS means of telaprevir Cmax and AUCinf were increased by 3% and 21%, respectively, compared to healthy subjects.

Gender

The effect of subject gender on telaprevir pharmacokinetics was eva luated using population pharmacokinetics of data from clinical trials of telaprevir. No dose adjustments are deemed necessary based on gender.

Race

Population pharmacokinetic analysis of telaprevir in HCV-infected subjects indicated that race had no apparent effect on the exposure to telaprevir.

Geriatric Use

Population pharmacokinetic analysis in HCV-infected subjects showed that within the age range (19-70 years) investigated (35 subjects 65 years of age and older), subject age did not have a clinically relevant effect on the exposure to telaprevir.

Pediatric Use

The pharmacokinetics of INCIVEK in pediatric patients have not been eva luated.

Drug Interactions

In vitro studies indicated that telaprevir is a substrate and inhibitor of CYP3A4 and a substrate and inhibitor of P-gp. No inhibition by telaprevir of CYP1A2, CYP2C9, CYP2C19, and CYP2D6 isozymes was observed in vitro. In vitro studies also suggest that telaprevir has a low potential to induce CYP2C, CYP3A, or CYP1A. Therefore, clinical studies were conducted to eva luate the effect of drugs that can affect or be affected by telaprevir during co-administration (Tables 6 and 7).

Table 6 Drug 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 day