*Patients receiving the 400 mg and 800 mg doses in the SC were down-dosed to receive 100 mg in an open-label fashion. Down dosing occurred in SC at various time points while on MK-5172. No patients were down-dosed in the VC.
The frequency and severity of ALT/AST elevations after TW 4 were dose dependent. The frequencies of ALT/AST elevations in the MK-5172 100 mg arm and the control arm after TW 4 were comparable at 2 percent each, (1/66) and (1/66), respectively.
The frequency of ALT/AST elevations observed in the MK-5172 200 mg, MK-5172 400 mg and MK-5172 800 mg arms after TW 4 were higher.
One patient in the MK-5172 800 mg arm experienced a serious adverse event due to elevated ALT and total bilirubin levels, which returned to normal after discontinuation of all therapy.
Important Safety Information about VICTRELIS (boceprevir)
All contraindications to PR also apply since VICTRELIS must be administered with PR. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with PR is contraindicated in pregnant women and in men whose female partners are pregnant. Avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; have monthly pregnancy tests; and use two or more forms of effective contraception, including intrauterine devices and barrier methods, during treatment and for at least 6 months after treatment has concluded. Systemic hormonal contraceptives may not be as effective in women while taking VICTRELIS (boceprevir). VICTRELIS is contraindicated in coadministration with drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
VICTRELIS also is contraindicated in coadministration with potent CYP3A4/5 inducers, where significantly reduced VICTRELIS plasma concentrations may be associated with reduced efficacy. Drugs that are contraindicated with VICTRELIS (boceprevir) include: alfuzosin, carbamazepine, phenobarbital, phenytoin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John's Wort (hypericum perforatum), lovastatin, simvastatin, drosperinone, Revatio
(sildenafil) or Adcirca
(tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and orally administered midazolam.
Anemia and/or Neutropenia -- The addition of VICTRELIS (boceprevir) to PR is associated with an additional decrease in hemoglobin concentrations compared to PR alone and/or may result in worsening of neutropenia associated with PR therapy alone. Dose reduction or discontinuation of peginterferon alfa and/or ribavirin may be required. Dose reduction of VICTRELIS is not recommended. VICTRELIS must not be administered in the absence of PR.