VIEKIRA XR(dasabuvir, ombitasvir, paritaprevir, and ritonavir)extended-release tablets(十一)
eline levels post-treatment. Two subjects had CD4+ T-cell counts decrease to less than 200 cells/mm3 during treatment without a decrease in CD4%. No subject experienced an AIDS-related opportunistic infection.
Components of VIEKIRA XR with Ribavirin in Selected Liver Transplant Recipients
The components of VIEKIRA XR with ribavirin were assessed in 34 post-liver transplant subjects with recurrent HCV infection. Adverse events occurring in more than 20% of subjects included fatigue 50%, headache 44%, cough 32%, diarrhea 26%, insomnia 26%, asthenia 24%, nausea 24%, muscle spasms 21% and rash 21%. Ten subjects (29%) had at least one post-baseline hemoglobin value of less than 10 g/dL. Ten subjects underwent a ribavirin dose modification due to decrease in hemoglobin and 3% (1/34) had an interruption of ribavirin. Five subjects received erythropoietin, all of whom initiated ribavirin at the starting dose of 1000 to 1200 mg daily. No subject received a blood transfusion [see Clinical Studies (14.5)].
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of the components of VIEKIRA XR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune System Disorders: Hypersensitivity reactions (including angioedema).
Hepatobiliary Disorders: Hepatic decompensation, hepatic failure [see Warnings and Precautions (5.2)].
7 DRUG INTERACTIONS
7.1 Potential for VIEKIRA XR to Affect Other Drugs
Dasabuvir, ombitasvir, and paritaprevir are inhibitors of UGT1A1, and ritonavir is an inhibitor of CYP3A4. Paritaprevir is an inhibitor of OATP1B1 and OATP1B3 and dasabuvir, paritaprevir, and ritonavir are inhibitors of BCRP. Co-administration of VIEKIRA XR with drugs that are substrates of CYP3A, UGT1A1, BCRP, OATP1B1 or OATP1B3 may result in increased plasma concentrations of such drugs [see also Contraindications (4), Warnings and Precautions (5.5), and Clinical Pharmacology (12.3)].
7.2 Potential for Other Drugs to Affect One or More Components of VIEKIRA XR
Paritaprevir and ritonavir are primarily metabolized by CYP3A enzymes. Co-administration of VIEKIRA XR with strong inhibitors of CYP3A may increase paritaprevir and ritonavir concentrations. Dasabuvir is primarily metabolized by CYP2C8 enzymes. Co-administration of VIEKIRA XR with drugs that inhibit CYP2C8 may increase dasabuvir plasma concentrations. Ombitasvir is primarily metabolized via amide hydrolysis while CYP enzymes play a minor role in its metabolism. Ombitasvir, paritaprevir, dasabuvir and ritonavir are substrates of P-gp. Ombitasvir, paritaprevir and dasabuvir are substrates of BCRP. Paritaprevir is a substrate of OATP1B1 and OATP1B3. Inhibition of P-gp, BCRP, OATP1B1 or OATP1B3 may increase the plasma concentrations of the various components of VIEKIRA XR.
7.3 Established and Other Potential Drug Interactions
If dose adjustments of concomitant medications are made due to treatment with VIEKIRA XR, doses should be re-adjusted after administration of VIEKIRA XR is completed. TABLE 5 provides the effect of co-administration of VIEKIRA XR on concentrations of concomitant drugs and the effect of concomitant drugs on the various components of VIEKIRA XR. Refer to Contraindications for drugs that are contraindicated with VIEKIRA XR [see Contraindications (4 |
