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GENVOYA(elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide)tablets(二十一)
of virologically suppressed subjects in an open-label trial, Study 112 (Table 8).
Table 8 Pharmacokinetics of GENVOYA in HIV-Infected Adults with Renal Impairment as Compared to Subjects with Normal Renal Function
AUCtau (microgram∙hour per mL)
Mean (CV%)
Creatinine Clearance ≥90 mL per minute (N=18)* 60–89 mL per minute (N=11)† 30–59 mL per minute (N=18)‡
* From a Phase 2 study in HIV-infected adults with normal renal function. † These subjects from Study 112 had an eGFR ranging from 60 to 69 mL per minute. ‡ Study 112. § AUC last
Elvitegravir 22.6 (35.8) 24.2 (35.0) 29.0 (29.6)
Cobicistat 9.4 (35.0) 10.0 (47.5) 9.9 (45.0)
Emtricitabine 11.4 (11.9) 17.6 (18.2) 23.0 (23.6)
Tenofovir Alafenamide§ 0.23 (47.2) 0.24 (45.6) 0.26 (58.8)
Tenofovir 0.32 (14.9) 0.46 (31.5) 0.61 (28.4)
Patients with Hepatic Impairment
Elvitegravir and Cobicistat: A study of the pharmacokinetics of elvitegravir (administered with the CYP3A inhibitor cobicistat) was performed in healthy subjects and subjects with moderate hepatic impairment. No clinically relevant differences in elvitegravir or cobicistat pharmacokinetics were observed between subjects with moderate hepatic impairment (Child-Pugh Class B) and healthy subjects [see USE IN SPECIFIC POPULATIONS (8.7)].
Emtricitabine: The pharmacokinetics of emtricitabine has not been studied in subjects with hepatic impairment; however, emtricitabine is not significantly metabolized by liver enzymes, so the impact of liver impairment should be limited.
Tenofovir Alafenamide (TAF): Clinically relevant changes in TAF and tenofovir pharmacokinetics were not observed in subjects with mild to moderate (Child-Pugh Class A and B) hepatic impairment [see USE IN SPECIFIC POPULATIONS (8.7)].
Hepatitis B and/or Hepatitis C Virus Co-infection
Elvitegravir: Limited data from population pharmacokinetic analysis (N=24) indicated that hepatitis B and/or C virus infection had no clinically relevant effect on the exposure of elvitegravir (administered with the CYP3A inhibitor cobicistat).
Cobicistat: There were insufficient pharmacokinetic data in the clinical trials to determine the effect of hepatitis B and/or C virus infection on the pharmacokinetics of cobicistat.
Emtricitabine and Tenofovir Alafenamide (TAF): Pharmacokinetics of emtricitabine and TAF have not been fully eva luated in subjects coinfected with hepatitis B and/or C virus.
Pediatric Patients
Exposures of TAF achieved in 24 pediatric subjects aged 12 to less than 18 years who received GENVOYA in Study 106 were decreased (23% for AUC) compared to exposures achieved in treatment-naïve adults following administration of GENVOYA, but were overall deemed acceptable based on exposure-response relationships; the other components of GENVOYA had similar exposures in adolescents compared to treatment-naïve adults [see USE IN SPECIFIC POPULATIONS (8.4)].
Geriatric Patients
Pharmacokinetics of elvitegravir, cobicistat, emtricitabine and tenofovir have not been fully eva luated in the elderly (65 years of age and older). Population pharmacokinetics analysis of HIV-infected subjects in Phase 2 and Phase 3 trials of GENVOYA showed that age did not have a clinically relevant effect on exposures of TAF up to 75 y |
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