The FDA ( Food and Drug Administration ) has approved Viread ( Tenofovir disoproxil fumarate ) for the treatment of chronic hepatitis B, a serious liver disease caused by the hepatitis B virus ( HBV ). Chronic hepatitis B is the leading cause of liver cancer worldwide and affects an estimated two million individuals in the United States.

Viread is administered as a once-daily tablet, and works by blocking HBV DNA polymerase, the enzyme that is necessary for the virus to replicate in liver cells. Viread has been available in the United States as a treatment for HIV infection in adults since 2001.

The approval is based on data from two ongoing, randomized and double-blind Phase III clinical trials, Studies 102 and 103, which compared Viread to Hepsera ( Adefovir dipivoxil ) over 48 weeks of treatment. Results from both studies show that a significantly greater percentage of patients with chronic hepatitis B who received Viread achieved a complete response to treatment compared to those who received Hepsera. A complete response was defined as serum HBV DNA levels below 400 copies/mL and histologic improvement characterized by at least a two point reduction in the Knodell necroinflammatory score with no concurrent worsening of fibrosis. Trial participants included both patients new to HBV therapy ( n=375 ) and patients ( n=51 ) who had received prior nucleoside treatment. To date, more than 400 chronic hepatitis B patients have been treated with Viread in these studies.

Because chronic HBV infection can persist for years without causing any noticeable symptoms, many people are unaware they are infected and do not seek treatment.

The following points should be considered when initiating therapy with Viread for the treatment of HBV infection:

-- This indication is based on data from one year of treatment in primarily nucleoside-treatment-naive adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease.

-- The numbers of patients in clinical trials who were nucleoside-experienced or who had Lamivudine-associated mutations at baseline was too small to reach conclusions of efficacy.

-- Viread has not been evaluated in patients with decompensated liver disease.

The recommended dose for the treatment of chronic hepatitis B is 300 mg once daily taken orally without regard to food. Dose interval adjustment is recommended in renal impairment.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals.

Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including Viread. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

New onset or worsening of renal impairment including cases of acute renal failure and Fanconi syndrome have been reported with the use of Viread. It is recommended to assess creatinine clearance ( CrCl ) before initiating treatment with Viread and monitor CrCl and serum phosphorus in patients at risk. Administering Viread with concurrent or recent use of nephrotoxic drugs, including Hepsera should be avoided.

HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with Viread. Viread should only be used as part of an appropriate antiretroviral combination regimen in HIV-infected patients with or without HBV coinfection.

Decreases in bone mineral density ( BMD ) have been observed in HIV-infected patients. It is recommended that BMD monitoring be considered for patients with a history of pathologic fracture or who are at risk for osteopenia. The bone effects of Viread have not been studies in patients with chronic HBV infection.

In controlled clinical trials in patients with chronic hepatitis B, the most common adverse reaction ( all grades ) is nausea. Other treatment-emergent adverse reactions reported in greater than 5 percent of patients treated with Viread included: abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain and skin rash.

The hepatitis B virus ( HBV ) is up to 100 times more easily transmitted than HIV. While most new cases of HBV infection in previously healthy adults are cleared by the immune system within a few months, many people - especially those infected as newborns and young children - will develop chronic, lifelong infections. In these cases, chronic hepatitis B can slowly destroy the liver, causing cirrhosis, liver disease, or liver cancer over many years or decades. Because it is believed to be the cause of 80 percent of all liver cancer cases worldwide, HBV is second only to tobacco among known human carcinogens.

The hepatitis B virus can be transmitted by any activity that involves exposure to blood and other body fluids, including sexual contact and use of contaminated needles during injection drug use. It can also be transmitted from mother to child at birth, which is the primary transmission route among Asian Americans.

Although there is no simple cure for chronic hepatitis B, antiviral treatment can slow viral replication and therefore reduce liver inflammation and liver injury.

Source: Gilead Sciences, 2008

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