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VIEKIRA XR(dasabuvir, ombitasvir, paritaprevir, and ritonavir)extended-release tablets(十)
t therapy was 3% (2/59).
ALT elevations were typically asymptomatic, generally occurred during the first 4 weeks of treatment (mean time 20 days, range 8-57 days) and most resolved with ongoing therapy. The majority of these ALT elevations were assessed as drug-related liver injury. Elevations in ALT were generally not associated with bilirubin elevations. Cirrhosis was not a risk factor for elevated ALT [see Warnings and Precautions (5.3)].
Serum Bilirubin Elevations
Post-baseline elevations in bilirubin at least 2 x ULN were observed in 15% of subjects receiving the components of VIEKIRA XR with ribavirin compared to 2% in those receiving the components of VIEKIRA XR without ribavirin. These bilirubin increases were predominately indirect and related to the inhibition of the bilirubin transporters OATP1B1/1B3 by paritaprevir and ribavirin-induced hemolysis. Bilirubin elevations occurred after initiation of treatment, peaked by study Week 1, and generally resolved with ongoing therapy. Bilirubin elevations were not associated with serum ALT elevations.
Anemia/Decreased Hemoglobin
Across all Phase 3 studies, the mean change from baseline in hemoglobin levels in subjects treated with the components of VIEKIRA XR with ribavirin was -2.4 g/dL and the mean change in subjects treated with the components of VIEKIRA XR without ribavirin was -0.5 g/dL. Decreases in hemoglobin levels occurred early in treatment (Week 1-2) with further reductions through Week 3. Hemoglobin values remained low during the remainder of treatment and returned towards baseline levels by post-treatment Week 4. Less than 1% of subjects treated with the components of VIEKIRA XR with ribavirin had hemoglobin levels decrease to less than 8.0 g/dL during treatment. Seven percent of subjects treated with the components of VIEKIRA XR with ribavirin underwent a ribavirin dose reduction due to a decrease in hemoglobin levels; three subjects received a blood transfusion and five required erythropoietin. One patient discontinued therapy due to anemia. No subjects treated with the components of VIEKIRA XR without ribavirin had a hemoglobin level less than 10 g/dL.
Components of VIEKIRA XR with Ribavirin in HCV/HIV-1 Co-infected Subjects
The components of VIEKIRA XR with ribavirin were assessed in 63 subjects with HCV/HIV-1 co-infection who were on stable antiretroviral therapy. The most common adverse events occurring in at least 10% of subjects were fatigue (48%), insomnia (19%), nausea (17%), headache (16%), pruritus (13%), cough (11%), irritability (10%), and ocular icterus (10%).
Elevations in total bilirubin greater than 2 x ULN (mostly indirect) occurred in 34 (54%) subjects. Fifteen of these subjects were also receiving atazanavir at the time of bilirubin elevation and nine also had adverse events of ocular icterus, jaundice or hyperbilirubinemia. None of the subjects with hyperbilirubinemia had concomitant elevations of aminotransferases [see Warnings and Precautions (5.6), Adverse Reactions (6.1) and Clinical Studies (14.6)]. No subject experienced a grade 3 ALT elevation.
Seven subjects (11%) had at least one post-baseline hemoglobin value of less than 10 g/dL, and six of these subjects had a ribavirin dose modification; no subject in this small cohort required a blood transfusion or erythropoietin.
Median declines in CD4+ T-cell counts of 47 cells/mm3 and 62 cells/mm3 were observed at the end of 12 and 24 weeks of treatment, respectively, and most returned to bas |
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