BETHESDA, MD 23 May 2011—Ten days after FDA approved the first hepatitis C virus (HCV) NS3/4A protease inhibitor, a second drug in the class has passed the agency's review for the treatment of adults with chronic HCV infection.
Telaprevir, which Vertex Pharmaceuticals expects to ship to pharmacies this week, will be sold as Incivek. Like boceprevir, which was approved May 13, the newer antiviral is indicated, in combination with peginterferon alfa and ribavirin, for the treatment of infections caused by HCV genotype 1 isolates.
Telaprevir is indicated for use in adults with compensated liver disease, including cirrhosis, whose infection has not been treated or has not responded to previous treatment with peginterferon alfa and ribavirin.
The recommended dosage described in the FDA-approved labeling (PDF) for telaprevir is two 375-mg tablets taken three times a day, preferably every seven to nine hours, with a fat-containing meal.
For the first 12 weeks of therapy, patients should undergo concomitant treatment with telaprevir, peginterferon alfa, and ribavirin. HCV DNA levels should be monitored after 4 and 12 weeks, and dual therapy with peginterferon alfa and ribavirin continued for an additional 12 or 36 weeks, depending on the degree of viral suppression, in patients who responded to the triple therapy.
If week 4 or week 12 HCV RNA levels exceed 1000 IU/mL using the assay recommended in the labeling, treatment should be discontinued after the initial 12 weeks of triple therapy.
The labeling for telaprevir includes a medication guide, but FDA did not require the creation of a risk evaluation and mitigation strategy for the drug.
The medication guide and labeling warn that telaprevir can harm or kill a developing fetus. The labeling states that women who use the drug must take a pregnancy test just before initiating telaprevir therapy and monthly thereafter and must use two forms of contraception. Female partners of male patients must avoid pregnancy for six months after treatment ends.
Medications that have a narrow therapeutic range and depend highly on a cytochrome P-450 isoeyzyme 3A for clearance are contraindicated in patients undergoing therapy with telaprevir. Many such drugs are listed in the labeling, as are other medications that may interact adversely with the HCV drug.
The most common adverse events associated with telaprevir use in clinical trials were itching, nausea, diarrhea, vomiting, taste changes, fatigue, and anal or rectal problems, according to the labeling.
Many clinical trial participants reported skin rashes, most of them mild, during treatment with telaprevir. Severe skin rashes, including Stevens-Johnson syndrome and drug rashes with eosinophilia and systemic symptoms, were reported by a small percentage of clinical trial participants. In some cases, the patients required hospitalization for the treatment of the rash.
The labeling advises patients to report signs of rash to their health care provider.
The labeling warns that telaprevir treatment increases patients' risk for anemia and recommends periodic blood tests to monitor hemoglobin levels.
Telaprevir is supplied as 375-mg capsules packaged in bottles of 168 tablets. The drug is also supplied in six-tablet blister strips, with each strip containing a day's worth of medication. The strips are packaged seven per carton, with four cartons constituting a single 28-day "packer" of the drug.
The drug should be stored at 25 degrees C, with excursions permitted to 15–30 degrees C.