Incivek™ (telaprevir) and Hepatitis C

What types of adverse reactions were reported when taking Incivek™?

UPDATE: As of August 2014 Vertex announced it will discontinue selling Incivek.

Serious drug reactions occurred in 3% of those subjects who received Incivek™ combination therapy and there were no reported adverse drug reactions in those in the study that were receiving peginterferon alfa and ribavirin alone.

14% of subjects discontinued Incivek™ due to adverse drug reactions, the most frequent being rash, anemia, fatigue, pruritus, nausea and vomiting.

The most common drug reactions to Incivek™ (an indidence at least 5% higher with Incivek™ than in controls) were rash, pruritus, anemia, nausea, hemorrhoids, diarrhea, anorectal discomforte, dysgeusia (alteration of taste), fatigue, vomiting and anal pruritus.

The most serious adverse reactions included skin disorders (rash and/or pruritus) and anemia.

Rash

Rash developed in 56% of study subjects who were in the study arm receiving Incivek™ triple therapy, only 34% of those in the study arm receiving just peginterferon alfa and ribavirin reported rash events. Rashes most frequently began during the first 4 weeks, however it could occur at any time during Incivek™ combination treatment. Severe rash was reported in 4% of subjects who received Incivek™ combination therapy compared to less than 1% of those in the study arm that received only peginterferon alfa and ribavirin.

Rash events led to the discontinuation of just Incivek™ in 6% of study subjects and discontinuation of the entire Incivek™ combination treatment in 1% of study subjects.

If one develops a mild to moderate rash they should be followed for progression of the rash. If the rash progresses and becomes severe or if systemic symptoms develop, Incivek™ should be discontinued although peginterferon alfa and ribavirin may be continued. If there is no improvement after discontinuation of Incivek™ within 7 days, then interruption or discontinuation of ribavirin and/or peginterferon alfa should be considered. It is possible, if medically indicated, that an earlier interruption or discontinuation of ribavirin and peginterferon alfa should be considered. Since Incivek™ dosage must not be reduced, if Incivek™ is discontinued due to rash it cannot be restarted.

Serious skin reactions were also reported including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson Syndrome (SJS) in less than 1% of subjects who received Incivek™ combination treatment. These serious skin reactions required hospitalization.

Anemia

While anemia has been reported with peginterferon alfa and ribavirin therapy, adding Incivek™ to this treatment created an additional decrease in hemoglobin concentrations. Of those subjects who received Incivek™ combination treatment, 36% had hemoglobin values less than or equal to 10 g/dL compared to 17% of those in the study receiving just peginterferon alfa and ribavirin. Furthermore, hemoglobin values less than 8.5 g/dL were reported in 14% of those receiving Incivek™ combination therapy versus 5% of those being treated in the study with just peginterferon alfa and ribavirin.

Of the participants of the study arm receiving Incivek™ combination therapy, 4% discontinued just Incivek™, 1% discontinued the entire Incivek™ triple therapy and 32% had a ribavirin dose modification (reduction, interruption or discontinuation) due to anemia. For those subjects of the study arm receiving just peginterferon alfa and ribavirin, 2 people discontinued and 12% had a ribavirin dose modification.

Vertex recommends that hemoglobin should be monitored prior to treatment with Incivek™ and at least every 4 weeks during Incivek ™ combination therapy. To manage anemia it is recommended that ribavirin dose reductions be used based on ribavirin dose reduction guidelines. If ribavirin dose reductions are not working, discontinuation of Incivek™ should be considered.  However, if ribavirin is permanently discontinued for the management of anemia, Incivek™ must be permanently discontinued as well and not restarted.

Other Adverse Reactions

There were anorectal events in 29% of subjects treated with Incivek™ combination treatment (compared to 7% being treated with just peginterferon alfa and ribavirin). The majority of these anorectal events included hemorrhoids, anorectal discomfort, anal pruritus and rectal burning which were mild to moderate in severity. Less than 1% of these events led to treatment discontinuation and all resolved during or after Incivek™ dosing.

Incivek™ treatment could cause decreases in white blood cell count as well as platelet counts, which is also the case with peginterferon alfa treatment.

Incivek™ treatment could increase bilirubin and uric acid levels.

Last Updated: July 2014