RESUMEN
: Product labels for cobicistat with atazanavir or darunavir, and for elvitegravir/cobicistat/emtricitabine/tenofovir (alafenamide or disoproxil fumarate) were recently updated to state that these products are not recommended for initiation during pregnancy, and an alternative regimen is recommended for those who become pregnant during therapy with these products. Herein, we present the rationale for these recommendations, which are based on studies in pregnant women evaluating the pharmacokinetics and antiviral activity of darunavir/cobicistat or elvitegravir/cobicistat-containing antiretroviral regimens. In these studies, mean steady-state minimum concentrations in the second and third trimester versus postpartum of cobicistat, darunavir, and elvitegravir were reduced by 61-83%, 89-92%, and 82-86%, respectively. In the absence of data with atazanavir/cobicistat, we leveraged the available data with darunavir/cobicistat and elvitegravir/cobicistat to make recommendations for atazanavir/cobicistat. Darunavir/ritonavir and atazanavir/ritonavir remain viable treatment options for pregnant women.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacocinética , Terapia Antirretroviral Altamente Activa/métodos , Cobicistat/administración & dosificación , Cobicistat/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Femenino , Humanos , Embarazo , Resultado del TratamientoRESUMEN
The development and ultimate approval of tecovirimat for the antiviral treatment of smallpox, a disease that has been eradicated from the world for nearly 40 years, required a unique regulatory approach based on the US Food and Drug Administration's Animal Rule. We summarise the regulatory pathway and describe the challenges involved.
Asunto(s)
Antivirales/uso terapéutico , Benzamidas/uso terapéutico , Aprobación de Drogas , Isoindoles/uso terapéutico , Viruela/tratamiento farmacológico , Erradicación de la Enfermedad , Humanos , Resultado del Tratamiento , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Single tablet, once-daily HIV treatment regimens offer patient convenience, the potential for increased adherence, and fewer patient-related dosing errors[1] . Stribild® (manufactured and marketed by Gilead Sciences; referred to as "applicant" in this report), a 4-drug fixed-dose combination (FDC) tablet, is approved for the treatment of HIV-1 infection in treatment-naïve adult patients. Stribild® contains elvitegravir (an integrase strand transfer inhibitor), cobicistat (an inhibitor of cytochrome P450 enzymes), and the nucleoside/nucleotide reverse transcriptase inhibitors emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF).