New Medications for Patients with Hepatitis C

Hepatitis C (HCV) was first discovered in 1989.  Prior to that time, it was called hepatitis A and non-B.  Approximately 4.0 million persons are infected with hepatitis C.  Many Americans have the disease but are unaware they have it. Hepatitis C is the major cause of chronic liver disease, cirrhosis and liver cancer.

The risk factors include: IV drug use, intranasal cocaine use, body piercings, tattoos, multiple sexual partners, blood transfusions before 1992 and possible military vaccinations.

There are multiple subsets of Hepatitis C called genotypes.  There are six subsets, 1 through 6.  Seventy-five percent of people with hepatitis C in the United States are infected with genotype 1 virus.  Patients with genotype 1 HCV are two to three-fold less likely to respond to the standard peg interferon alfa (peg IFN) and ribavirin (RBV) combination treatment than patients with genotype 2 or 3.  About 40% to 50% of the patients with genotype 1 HCV achieve sustained viral response (SVR) with peg IFN/RBV meaning that there is no detectable virus in the blood.

The HCV virus uses existing machinery inside the liver cell to read its RNA and produce proteins to build new virus particles, known as virons.  Interferon alfa promotes increased expression of proteins that interfere with viral replication.  Ribavirin enhances the antiviral effect of interferon; its precise mechanism of action is not certain.  Telaprevir (Incivek) and boceprevir (Victrelis) directly and specifically inhibit the HCV NS 3/4A serine protease, thereby halting viral replication.

Incivek (telaprevir)

Incivek, in combination with peg interferon alfa and ribavirin, is indicated for genotype 1 HCV in adults with functioning liver disease, including cirrhosis, who have never been treated or who have previously been treated with interferon-based treatment, but did not clear the virus or cleared the virus during treatment but then returned after stopping the medication.

Incivek has been evaluated in three adequate and well-controlled phase III trials in adult patients with genotype 1 chronic HCV: ADVANCE study, ILLUMINATE study and REALIZE study.  Incivek was administered at a dosage of 750 mg every eight weeks.  Patients in all three studies also received peg IFN and ribavirin.  Incivek had a cure rate of 79% in all populations.

Victrelis (boceprevir)

Victrelis is also indicated for chronic HCV genotype 1 infection in combination with peg Intron/Ribavirin in adult patients (18 years and older) with functioning liver disease, including cirrhosis, who are previously untreated or who have failed previous treatment.  Non-responders were not included in these studies.  Victrelis has been evaluated in two adequate and well controlled phase III trials: Sprint-2 using previously untreated patients and Respond-2 using patients who have failed previous therapy.  The cure rate in both studies was 66% with a relapse rate of 12%.

The recommended dose of Incivek is 750 mg taken orally three times per day (7-9 hours apart) with fatty foods.  It must not be administered as single therapy and must only be prescribed with peg-IFN/RBV.  To prevent treatment failure, the dose of Incivek must not be reduced or interrupted.

Patients who have never been treated (naïve) and prior relapsers can complete treatment if they have no detectable virus at week four and 12 at 24 weeks.  Treatment-naïve with cirrhosis, prior non and current responders are treated for 48 weeks.

The recommended dosage for Victrelis is 800 mg three times daily (every 7-9 hours with a meal or a light snack.  It also must be administered in combination with peg-IFN/RBV.  This treatment program initially starts with only peg-IFN/RBV, then on week five Victrelis is started.  Treatment-naïve, relapsers and partial responders without cirrhosis that have no detectable virus at week eight and 24 can stop treatment at week 36.  Patients with cirrhosis must complete 48 weeks of treatment.

Side effects for both drugs are: rash, fatigue, pruritus, nausea, anemia, diarrhea, vomiting, hemorrhoids, rectal discomfort, metallic taste and anal itching.  Incivek has a higher incidence of a skin rash than Victrelis.  Victrelis, on the other hand, has a higher reported incidence of anemia.

Contraindications for both protease inhibitors are: women who are or may become pregnant, men whose female partners are pregnant, drugs that are metabolized by a specific liver enzyme called CYP3A.  It is important to tell your doctor all your medications, over-the-counter and prescribed, so that potential interactions can be avoided.

Tina M. Navitsky, CRNP