ng treatment of adult subjects with the combination of VICTRELIS with PegIntron and REBETOL are described in Table 4.
Hemoglobin
Decreases in hemoglobin may require a decrease in dosage/interruption or discontinuation of ribavirin [see Warnings and Precautions (5.2) and Clinical Studies (14); see Package Insert for ribavirin].
Neutrophils and Platelets
The proportion of subjects with decreased neutrophil and platelet counts was higher in the VICTRELIS-containing arms compared to subjects receiving PegIntron/REBETOL alone. Three percent of subjects receiving the combination of VICTRELIS with PegIntron/REBETOL had platelet counts of less than 50 × 109/L compared to 1% of subjects receiving PegIntron/REBETOL alone. Decreases in neutrophils or platelets may require a decrease in dosage or interruption of peginterferon alfa, or discontinuation of therapy [see Package Inserts for peginterferon alfa and ribavirin].
Table 4 Selected Hematological Parameters
|
|
Previously Untreated
(SPRINT-1 & SPRINT-2) |
Previous Treatment Failures
(RESPOND-2) |
|
|
Percentage of Subjects Reporting Selected Hematological Parameters |
Percentage of Subjects Reporting Selected Hematological Parameters |
|
Hematological Parameters |
VICTRELIS + PegIntron + REBETOL
(n=1225) |
PegIntron + REBETOL
(n=467) |
VICTRELIS + PegIntron + REBETOL
(n=323) |
PegIntron + REBETOL
(n=80) |
|
Hemoglobin (g/dL) |
|
<10 |
49 |
29 |
49 |
25 |
|
<8.5 |
6 |
3 |
10 |
1 |
|
Neutrophils (× 109/L) |
|
<0.75 |
31 |
18 |
26 |
13 |
|
<0.5 |
8 |
4 |
7 |
4 |
|
Platelets (× 109/L) |
|
<50 |
3 |
1 |
4 |
0 |
|
<25 |
<1 |
0 |
0 |
0 |
7 DRUG INTERACTIONS
See also Contraindications (4), Warnings and Precautions (5.4), and Clinical Pharmacology (12.3).
7.1Potential for VICTRELIS to Affect Other Drugs
Boceprevir is a strong inhibitor of CYP3A4/5. Drugs metabolized primarily by CYP3A4/5 may have increased exposure when administered with VICTRELIS, which could increase or prolong their therapeutic and adverse effects. Boceprevir does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 in vitro. In addition, boceprevir does not induce CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or CYP3A4/5 in vitro.
Boceprevir is a potential inhibitor of p-glycoprotein (P-gp) based on in vitro studies. The potential for a drug interaction with sensitive substrates of p-glycoprotein (e.g., digoxin) has not been eva luated in a clinical trial.
7.2Potential for Other Drugs to Affect VICTRELIS
Boceprevir is primarily metabolized by aldo-ketoreductase (AKR). In drug interaction trials conducted with AKR inhibitors diflunisal and ibuprofen, boceprevir exposure did not increase to a clinically significant extent. VICTRELIS may b
