Embryofetal RTV 15 8.46 0.9 development PAR 100 45.2 65 (main GD17 RTV 15 8.22 0.9 PAR 450 58.6 8 RTV 45 26.2 2.8 Mouse Embryofetal PAR 30 224 32 development CD-1 PAR 100 631 90 (main study) GD15 PAR 300 686 98 RTV 30 49.7 5.2 Rat Pre/postnatal PAR 30 0.345* 0.05 (Crl:CD1[ICR]) development RTV 30 18.1* 1.9 PAR 60 5.36* 0.8 RTV 30 20.2* 2 PAR 300 116* 17 RTV 30 17* 1.8 Human (healthy steady PAR 150 mg/day 6.99 – volunteers) Human (healthy steady state 100 mg/day 9.47 - volunteers) RTV # = animal: human plasma AUC0–24 h. * = maternal plasma AUC Pregnancy classification The sponsor has proposed Pregnancy Category B1 for paritaprevir. The reference regarding animal data in the pregnancy category statement for B1 is consistent with the results from the nonclinical assessment. This category would be appropriate if the clinical data indicates that paritaprevir has indeed been taken by a limited number of pregnant women and women of childbearing age without an evidence of an increase in the frequency of malformation or indirect harmful effects. When combined with ritonavir (Pregnancy Category B3) or ribavirin (Pregnancy Category X) then the higher pregnancy category takes precedence. This is discussed in the evaluation of the combination products Viekira Pak and Viekira Pak–RBV. Photosafety No nonclinical phototoxicity studies have been submitted based on supporting clinical safety information from Phase III clinical studies. Although paritaprevir absorbs light in the
Embryofetal development (main GD17 RTV 15 8.46 0.9 PAR 100 45.2 65 RTV 15 8.22 0.9 PAR 450 58.6 8 RTV 45 26.2 2.8 Mouse CD-1 Embryofetal development (main study) GD15 PAR 30 224 32 PAR 100 631 90 PAR 300 686 98 RTV 30 49.7 5.2 Rat (Crl:CD1[ICR]) Pre/postnatal development PAR 30 0.345* 0.05 RTV 30 18.1* 1.9 PAR 60 5.36* 0.8 RTV 30 20.2* 2 PAR 300 116* 17 RTV 30 17* 1.8 Human (healthy volunteers) steady PAR 150 mg/day 6.99 – Human (healthy volunteers) steady state RTV 100 mg/day 9.47 - # = animal: human plasma AUC0–24 h. * = maternal plasma AUC Pregnancy classification The sponsor has proposed Pregnancy Category B1 for paritaprevir. The reference regarding animal data in the pregnancy category statement for B1 is consistent with the results from the nonclinical assessment. This category would be appropriate if the clinical data indicates that paritaprevir has indeed been taken by a limited number of pregnant women and women of childbearing age without an evidence of an increase in the frequency of malformation or indirect harmful effects. When combined with ritonavir (Pregnancy Category B3) or ribavirin (Pregnancy Category X) then the higher pregnancy category takes precedence. This is discussed in the evaluation of the combination products Viekira Pak and Viekira Pak–RBV. Photosafety No nonclinical phototoxicity studies have been submitted based on supporting clinical safety information from Phase III clinical studies. Although paritaprevir absorbs light in the
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