ax and AUC24,ss values
b Relative to healthy subjects, glecaprevir Cmax was 51% lower and AUC24,ss was similar (10% difference) in HCV-infected subjects without cirrhosis, respectively
c Relative to healthy subjects, pibrentasvir Cmax and AUC24,ss were 63% and 34% lower, respectively in HCV-infected subjects without cirrhosis, respectively
Specific Populations
Pediatric Patients
The pharmacokinetics of MAVYRET in pediatric patients has not been established.
Subjects with Renal Impairment
Glecaprevir and pibrentasvir AUC were increased ≤ 56% in non-HCV infected subjects with mild, moderate, severe, or end-stage renal impairment (GFR estimated using Modification of Diet in Renal Disease) not on dialysis compared to subjects with normal renal function. Glecaprevir and pibrentasvir AUC were similar with and without dialysis (≤ 18% difference) in dialysis-dependent non-HCV infected subjects. In HCV-infected subjects, 86% higher glecaprevir and 54% higher pibrentasvir AUC were observed for subjects with end stage renal disease, with or without dialysis, compared to subjects with normal renal function.
Subjects with Hepatic Impairment
Following administration of MAVYRET in HCV infected subjects with compensated cirrhosis (Child-Pugh A), exposure of glecaprevir was approximately 2-fold and pibrentasvir exposure was similar to non-cirrhotic HCV infected subjects.
At the clinical dose, compared to non-HCV infected subjects with normal hepatic function, glecaprevir AUC 100% higher in Child-Pugh B subjects, and increased to 11-fold in Child-Pugh C subjects. Pibrentasvir AUC was 26% higher in Child-Pugh B subjects, and 114% higher in Child-Pugh C subjects.
Age/Gender/Race/Body Weight
No clinically significant differences in the pharmacokinetics of glecaprevir or pibrentasvir were observed based on age [18-88 years], sex, race/ethnicity or body weight.
Drug Interaction Studies
Drug interaction studies were performed with glecaprevir/pibrentasvir and other drugs that are likely to be coadministered and with drugs commonly used as probes for pharmacokinetic interactions. Tables 8 and 9 summarize the pharmacokinetic effects when glecaprevir/pibrentasvir was coadministered with other drugs which showed potentially clinically relevant changes. Significant interactions are not expected when MAVYRET is coadministered with substrates of CYP3A, CYP1A2, CYP2C9, CYP2C19, CYP2D6, UGT1A1, or UGT1A4.
Table 8. Drug Interactions: Changes in Pharmacokinetic Parameters of Glecaprevir (GLE) or Pibrentasvir (PIB) in the Presence of Coadministered Drug
Co-
administered
Drug Regimen
of Co-
administered
Drug (mg) Regimen
of
GLE/PIB
(mg) N DAA Central Value Ratio
(90% CI)
Cmax AUC Cmin
Atazanavir +
ritonavir 300 + 100
once daily 300/120
once dailya 12 GLE ≥4.06
(3.15, 5.23) ≥6.53
(5.24, 8.14) ≥14.3
(9.85, 20.7)
PIB ≥1.29
(1.15, 1.45) ≥1.64
(1.48, 1.82) ≥2.29
(1.95, 2.68)
Carbamazepine 200 twice
daily 300/120
single dose 10 GLE 0.33
(0.27, 0.41) 0.34
(0.28, 0.40) --
PIB 0.50
(0.42, 0.59) 0.49
(0.43, 0.55) --
Cyclosporine 100 single
dose 300/120
once daily 12 GLE 1.30
(0.95, 1.78) 1.37
(1.13, 1.66)&nb |
