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VIEKIRA XR(dasabuvir, ombitasvir, paritaprevir, and ritonavir)extended-release tablets(十五)
inical dose.
In a pre- and postnatal developmental study in rats, dasabuvir was administered orally at 0, 50, 200, or 800 mg/kg/day from GD 7 to lactation day 21. There were no treatment-related effects at maternal exposures 44-times higher than exposures in humans at the recommended clinical dose.
Ombitasvir
Ombitasvir was administered orally to pregnant mice (0, 15, 50, or 150 mg/kg/day) and rabbits (0, 10 or 60 mg/kg/day) during the period of organogenesis (on gestation days (GD) 6 to 15, and GD 7 to 19, respectively). There were no ombitasvir-related embryofetal effects (malformations or fetal toxicity) at any dose level in either species. The systemic exposures at the highest doses were 28-times higher (mice) and 4-times higher (rabbits) than the exposures in humans at the recommended clinical dose.
In a pre- and postnatal developmental study in mice, ombitasvir was administered orally at 0, 10, 40, or 200 mg/kg/day from GD 6 to lactation day 20. There were no ombitasvir-related effects at maternal exposures 25-times higher than exposures in humans at the recommended clinical dose.
The major human metabolites of ombitasvir, M29 and M36, were tested in pregnant mice during the period of organogenesis from GD 6 to 15. M29 was administered orally at doses of 0, 1, 2.5 or 4.5 mg/kg/day. M36 was dosed orally at doses 1.5, 3, or 6 mg/kg/day. In both cases, there were no treatment related embryofetal effects (malformations or fetal toxicity) at any dose level. The highest doses produced exposures approximately 26-times higher than the exposures in humans at the recommended clinical dose.
Paritaprevir/ritonavir
Paritaprevir/ritonavir was administered orally to pregnant rats (0/0, 30/15, 100/15, 450/45 mg/kg/day) and mice (0/0, 30/30, 100/30, or 300/30 mg/kg/day) during the period of organogenesis (on GD 6 to 17, and GD 6 to 15, respectively). There were no test article-related embryofetal effects (malformations or fetal toxicity) at any dose level in either species. The highest systemic exposure of paritaprevir was 8-times higher (rats) and 98-times higher (mice) than the exposures in humans at the recommended clinical dose.
In a pre- and postnatal developmental study in rats, paritaprevir/ritonavir were administered orally at 0/0, 6/30, 30/30, or 300/30 mg/kg/day from GD 7 to lactation day 20. There were no treatment related effects at maternal exposures 17-times higher than exposures in humans at the recommended clinical dose.
8.2 Lactation
Risk Summary
It is not known whether VIEKIRA XR and its metabolites are present in human breast milk, affect human milk production or have effects on the breastfed infant. Unchanged ombitasvir, paritaprevir and its hydrolysis product M13, and dasabuvir were the predominant components observed in the milk of lactating rats, without effect on nursing pups [see Data].
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VIEKIRA XR and any potential adverse effects on the breastfed child from VIEKIRA XR or from the underlying maternal condition.
If VIEKIRA XR is administered with ribavirin, the nursing mother’s information for ribavirin also applies to this combination regimen. Refer to the ribavirin prescribing information for more information on use during lactation.
Data
Animal Data
Dasabuvir
No effects of dasabuvir on growth and postnatal development were observed in nursing pups at the highest dose tested (800 |
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