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GENVOYA(elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide)tablets(十六)
ed in the offspring on gestation day 7 [and lactation day 20] at tenofovir exposures of approximately 14 [21] times higher than the exposures in humans at the recommended daily dose of GENVOYA.
8.2 Lactation
Risk Summary
The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.
Based on published data, emtricitabine has been shown to be present in human breast milk; it is unknown if elvitegravir, cobicistat, and TAF are present in human breast milk. Elvitegravir and cobicistat are present in rat milk, and tenofovir has been shown to be present in the milk of lactating rats and rhesus monkeys after administration of TDF [see DATA]. It is unknown if TAF is present in animal milk.
It is not known if GENVOYA affects milk production or has effects on the breastfed child. Because of the potential for 1) HIV transmission (in HIV-negative infants); 2) developing viral resistance (in HIV-positive infants); and 3) adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are receiving GENVOYA.
Data
Animal Data
Elvitegravir: During the pre/postnatal developmental toxicology study at doses up to 2000 mg/kg/day, a mean elvitegravir milk to plasma ratio of 0.1 was measured 30 minutes after administration to rats on lactation day 14.
Cobicistat: During the pre/postnatal developmental toxicology study at doses up to 75 mg/kg/day, mean cobicistat milk to plasma ratio of up to 1.9 was measured 2 hours after administration to rats on lactation day 10.
Tenofovir Alafenamide: Studies in rats and monkeys have demonstrated that tenofovir is secreted in milk. During the pre/postnatal developmental toxicology study, tenofovir was excreted into the milk of lactating rats following oral administration of TDF (up to 600 mg/kg/day) at up to approximately 24% of the median plasma concentration in the highest dosed animals at lactation day 11. Tenofovir was excreted into the milk of lactating rhesus monkeys, following a single subcutaneous (30 mg/kg) dose of tenofovir, at concentrations up to approximately 4% of plasma concentration resulting in exposure (AUC) of approximately 20% of plasma exposure.
8.4 Pediatric Use
The efficacy and safety of GENVOYA for the treatment of HIV-1 infection was established in pediatric patents aged 12 years and older with body weight greater than or equal to 35 kg [see DOSAGE AND ADMINISTRATION (2.2)]. Use of GENVOYA in this age group is supported by studies in adults and by an open-label trial of 50 antiretroviral treatment-naïve HIV-1 infected pediatric subjects 12 to less than 18 years old receiving GENVOYA through Week 48 (Study 106). The safety and efficacy of GENVOYA in these subjects was similar to that in antiretroviral treatment-naïve adults [see ADVERSE REACTIONS (6.1), CLINICAL PHARMACOLOGY (12.3), and CLINICAL STUDIES (14.5)].
Safety and effectiveness of GENVOYA in pediatric patients less than 12 years of age or less than 35 kg have not been established.
8.5 Geriatric Use
Clinical trials of GENVOYA included 97 subjects (80 receiving GENVOYA) aged 65 years and over. No differences in safety or efficacy have been observed between elderly subjects and those between 12 and less than 65 years of age.
8.6 Renal Impairment
The pharmacokinetics, safety, and virologic and immunologic responses of GENVOYA in HIV-1 infected adult subjects with renal impairment (eGF |
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