If HARVONI is administered with ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partners are pregnant. Describe the ribavirin recommending information for more information on ribavirin-associated threats of use during pregnancy.
No adequate human data are offered to establish whether or not HARVONI poses a risk to pregnancy results.
In animal recreation studies, no evidence of unfavorable developmental results was observed with the components of HARVONI (ledipasvir or sofosbuvir) at direct exposures than those in people at the recommended human dosage (RHD).
During organogenesis in the rat and bunny, systemic exposures (AUC) to ledipasvir were roughly 4 (rats) and 2 (rabbits) times the direct exposure in human beings at the RHD, while exposures to the predominant flowing metabolite of sofosbuvir (GS-331007) were ≥ 3 (rats) and 7 (rabbits) times the exposure in human beings at the RHD.
In rat pre/postnatal development research studies, maternal systemic direct exposures (AUC) to ledipasvir and GS-331007 were approximately 5 and 7 times, respectively, the direct exposure in human beings at the RHD.
The background risk of significant abnormality and miscarriage for the suggested population is unidentified. In the U.S. basic population, the estimated background risk of significant abnormality and miscarriage in medically acknowledged pregnancies is 2– 4% and 15– 20%, respectively.
Data
Animal Data
Ledipasvir: Ledipasvir was administered orally to pregnant rats (approximately 100 mg/kg/day) and rabbits (up to 180 mg/kg/day) on gestation days 6 to 18 and 7 to 20, respectively, and also to rats (oral doses up to 100 mg/kg/day) on gestation day 6 to lactation/post-partum day 20.
No substantial results on embryo-fetal (rats and bunnies) or pre/postnatal (rats) development were observed at the greatest dosages checked. Systemic exposures (AUC) to ledipasvir were ≥ 4 (rats) and 2 (bunnies) times the direct exposure in human beings at the RHD.
Sofosbuvir: Sofosbuvir was administered orally to pregnant rats (approximately 500 mg/kg/day) and rabbits (approximately 300 mg/kg/day) on pregnancy days 6 to 18 and 6 to 19, respectively, as well as to rats (oral doses up to 500 mg/kg/day) on gestation day 6 to lactation/post-partum day 20.
No significant results on embryo-fetal (rats and bunnies) or pre/postnatal (rats) development were observed at the highest dosages checked. Systemic exposures (AUC) to the primary circulating metabolite of sofosbuvir (GS-331007) were ≥ 3 (rats) and 7 (rabbits) times the direct exposure in people at the RHD, with exposures increasing during pregnancy from around 3 to 6 (rats) and 7 to 17 (bunnies) times the direct exposure in people at the RHD.
Lactation
It is unknowned whether ledipasvir or sofosbuvir, the elements of HARVONI, or their metabolites are present in human breast milk, affect human milk production or have effects on the breastfed baby.
When administered to lactating rats, ledipasvir was identified in the plasma of nursing puppies likely due to the existence of ledipasvir in milk, without clear impacts on nursing puppies. The predominant distributing metabolite of sofosbuvir (GS-331007) was the primary part observed in the milk of breast feeding rats, without result on nursing puppies.
The development and health advantages of breastfeeding ought to be thought about in addition to the mother’s clinical requirement for HARVONI and any prospective adverse results on the breastfed child from HARVONI or from the underlying maternal condition.
If HARVONI is administered with ribavirin, the nursing mother’s info for ribavirin likewise uses to this mix routine. Describe the ribavirin recommending information for more details on use during lactation.
Information
Ledipasvir: No results of ledipasvir on growth and postnatal development were observed in nursing pups at the highest dosage evaluated in rats. Maternal systemic direct exposure (AUC) to ledipasvir was roughly 5 times the exposure in people at the RHD.
Although not measured straight, ledipasvir was likely present in the milk of lactating rats, because systemic direct exposure (AUC) to ledipasvir of roughly 25% that of maternal exposure was observed in nursing puppies on lactation day 10.
Sofosbuvir: No impacts of sofosbuvir on growth and postnatal development were observed in nursing puppies at the highest dose checked in rats. Maternal systemic direct exposure (AUC) to the predominant distributing metabolite of sofosbuvir (GS-331007) was roughly 7 times the direct exposure in people at the RHD, with exposure of roughly 2% that of maternal exposure observed in nursing pups on lactation day 10.
In a lactation research study, sofosbuvir metabolites (primarily GS-331007) were excreted into the milk of breast feeding rats following administration of a single oral dose of sofosbuvir (20 mg/kg) on lactation day 2, with milk concentrations of around 10% that of maternal plasma concentrations observed 1 hour post-dose.
Females and Males of Reproductive Potential
If HARVONI is administered with ribavirin, the details for ribavirin with regard to pregnancy testing, contraception, and infertility likewise applies to this combination regimen. Describe ribavirin recommending information for extra information.
Renal Impairment
No dosage adjustment of HARVONI is needed for patients with mild or moderate kidney problems. The safety and efficacy of HARVONI have not been established in patients with severe kidney problems (eGFR less than 30 mL/min/1.73 m2) or ESRD requiring hemodialysis.
No dosage recommendation can be given for patients with severe kidney disability or ESRD. Describe ribavirin recommending details concerning use in patients with renal disability.
Hepatic Impairment
No dosage adjustment of HARVONI is required for patients with mild, moderate, or severe hepatic disability (Child-Pugh Class A, B, or C), Clinical Pharmacology.
Medical and hepatic laboratory monitoring, as scientifically suggested, is recommended for patients with decompensated cirrhosis getting treatment with HARVONI and ribavirin.
Good luck! Have a nice weekend!
