Victrelis( Boceprevir ) has been approved by the FDA ( Food and Drug Administration ) for the treatment of chronic hepatitis C genotype 1 infection, in combination with Peginterferon alfa and Ribavirin, in adult patients ( 18 years of age and older ) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous Interferon and Ribavirin therapy.

The following points should be considered when initiating Boceprevir for treatment of chronic hepatitis C infection: Boceprevir must not be used as monotherapy and should only be used in combination with Peginterferon alfa and Ribavirin; Boceprevir efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes Boceprevir or other HCV NS3/4A protease inhibitors.
Boceprevir in combination with Peginterferon alfa and Ribavirin has not been studied in patients documented to be historical null responders ( less than a 2 log HCV-RNA decline by treatment week 12 ) during prior therapy with Peginterferon alfa and Ribavirin. The clinical studies included patients who were poorly Interferon responsive. Patients with less than 0.5 log HCV-RNA decline in viral load at treatment week 4 with Peginterferon alfa plus Ribavirin alone are predicted to have a null response ( less than a 2 log HCV-RNA decline by treatment week 12 ) to Peginterferon alfa and Ribavirin therapy.
Poorly Interferon responsive patients who were treated with Boceprevir in combination with Peginterferon alfa and Ribavirin have a lower likelihood of achieving a sustained virologic response ( SVR ), and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to Peginterferon alfa and Ribavirin.

All contraindications to Peginterferon alfa and Ribavirin also apply since Boceprevir must be administered with Peginterferon alfa and Ribavirin. Because Ribavirin may cause birth defects and fetal death, Boceprevir in combination with Peginterferon alfa and Ribavirin 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 Boceprevir.

Boceprevir 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. Boceprevir also is contraindicated in coadministration with potent CYP3A4/5 inducers where significantly reduced Boceprevir plasma concentrations may be associated with reduced efficacy. Drugs that are contraindicated with 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 Midazolam ( orally administered ).

Anemia has been reported with Peginterferon alfa and Ribavirin therapy. The addition of Boceprevir to Peginterferon alfa and Ribavirin is associated with an additional decrease in hemoglobin concentrations. The addition of Boceprevir may result in a worsening of neutropenia associated with Peginterferon alfa and Ribavirin alone. Complete blood counts should be obtained pretreatment, and at treatment weeks 4, 8 and 12, and should be monitored closely at other time points, as clinically appropriate. If a patient has a serious adverse reaction potentially related to Peginterferon alfa and Ribavirin therapy, the Peginterferon alfa and/or Ribavirin dose should be reduced or discontinued. Boceprevir must not be administered in the absence of Peginterferon alfa and Ribavirin. Dose reduction of Boceprevir is not recommended.

The most commonly reported adverse reactions ( greater than 35% ) in clinical trials in adult patients receiving the combination of Boceprevir with Peginterferon alfa-2b and Ribavirin were fatigue, anemia, nausea, headache and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates greater than or equal to 5% above the rates for Peginterferon alfa and Ribavirin alone in either clinical study. The incidence of these adverse reactions in previously untreated patients who received Boceprevir combination therapy compared with Peginterferon and Ribavirin alone were: fatigue ( 58 vs 59% ), anemia ( 50 vs 30% ), nausea ( 46 vs 42% ), dysgeusia ( 35 vs 16% ), respectively. The incidence of these adverse reactions in previously treated patients who received Boceprevir combination therapy compared with Peginterferon and Ribavirin alone were: fatigue ( 55 vs 50% ), anemia ( 45 vs 20% ), nausea ( 43 vs 38% ), dysgeusia ( 44 vs 11% ), respectively.

Boceprevir is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for drug-drug interactions must be considered prior to and during therapy.

Source: Merck, 2011

XagenaMedicine2011


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