General measures listed BAY 57-1293 for treatment of grade 1 rashes can be employed. If a grade 2 rash progresses despite these measures, it is recommended that telaprevir be discontinued. In a patient with stable grade 2 rash not responding to conservative measures, one could consider temporarily withdrawing ribavirin, as it may be difficult to confidently distinguish rash secondary to telaprevir from that induced by ribavirin or even interferon. Despite the long half-life of ribavirin, it has been reported that withdrawing it for as short as 48 hours may result in resolution of the rash.20 Grade

3 rash (severe) involves more than 50% of the integument or any of the following: vesicles/bullae, any ulceration of mucous membranes, epidermal detachment, targetoid lesion, or palpable purpura. Management of grade 3 rash includes immediate discontinuation of telaprevir, followed by ribavirin/pegylated interferon for nonresolution, and consideration of dermatology consultation. Stevens Johnson Syndrome, toxic epidermal necrolysis syndrome (TENS), erythema multiforme, and drug-related eosinophilia with systemic symptoms

(DRESS) also constitute grade 3 rash, which merit discontinuation of all 3 agents. The DRESS syndrome rash may present with fever, facial edema, hypereosinophilia, and liver www.selleckchem.com/products/PD-0332991.html (elevated liver tests/hepatomegaly) or renal dysfunction.21, 22 Once telaprevir has been discontinued, it should not be restarted. Of note, systemic steroids to allow continued telaprevir dosing should be avoided for rash management, because its impact on rash progression and viral breakthrough have not been assessed. The next most common side effect

is anemia. On average, the addition of telaprevir to PR results in an additional 1 g/dL decline in hemoglobin, in addition to the mean maximal drop of 3 g/dL Reverse transcriptase from pegylated interferon and ribavirin. In phase 3 studies, anemia with hemoglobin <10 g/dL occurred in 36% of patients on telaprevir versus 17% on SOC. The incidence of more severe anemia with a hemoglobin <8.5 g/dL was 14% with telaprevir compared to 5% with SOC. These resulted in dose reduction, interruption or discontinuation of ribavirin in approximately one-third of patients and discontinuation of telaprevir in 4%. The rate of decline of hemoglobin during weeks 1-4 is not any steeper with triple therapy than with SOC. In those receiving telaprevir, however, there is a continued decline between weeks 4 and 8. In theory, anemia of ribavirin should be distinguishable from that of telaprevir by markers of hemolysis. In practice, however, whether such a distinction is going to be helpful in clinical decision making remains uncertain. The most important principle to remember is that telaprevir cannot be dose-reduced or interrupted. Once it is stopped, it should not be restarted.