General Information

Viread (tenofovir disoproxil fumarate) is an oral nucleotide analogue DNA polymerase inhibitor. DNA polymerase is the enzyme that is necessary for the virus to replicate in liver cells.

Viread is specifically indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older weighing at least 10 kg.

Viread is specifically indicated for the treatment of chronic hepatitis B in adults. Viread has not been evaluated in patients with decompensated liver disease.

Prior to or when initiating Viread, test patients for HBV infection and HIV-1 infection. Viread alone should not be used in patients with HIV-1 infection

Viread is supplied as a tablet designed for oral administration. Dosing recommendations are the same for both indications. The recommended initial dose of the drug is 300 mg once daily taken orally, without regard to food.

The dosing interval of Viread should be adjusted in patients with baseline creatinine clearance <50 mL/min using the following recommendations:
Creatinine Clearance <50 mL/min recommended 300 mg dosing interval is every 24 hours.
Creatinine Clearance 30-49 mL/min recommended 300 mg dosing interval is every 48 hours.
Creatinine Clearance 10-29 mL/min recommended 300 mg dosing interval is every 72 to 96 hours.

In hemodialysis patients the recommended 300 mg dosing interval is every 7 days or after a total of approximately 12 hours of dialysis.

Clinical Results

HIV: Approval of Viread is supported by placebo-controlled clinical studies conducted with more than 1,000 HIV positive subjects. Viread was administered both alone and in combination with subjects' existing antiretroviral regimens. When used in addition to other antiretroviral products, Viread was shown to reduce the level of HIV in the blood for up to 48 weeks and to reduce the viral load even in subjects whose HIV had previously developed resistance to available antiretroviral medications. Resistance to Viread was rare and slow to develop.

HBV: 

FDA approval of Viread was based on the results of two phase III clinical trials.

HBeAg-Negative Chronic Hepatitis B
This randomized, double-blind, active-controlled study, dubbed Study 0102, enrolled 375 subjects with HBeAg- (anti-HBe+) Hepatitis B and compensated liver function. At baseline, the mean Knodell necroinflammatory score was 7.8; mean plasma HBV DNA was 6.9 log10 copies/mL; and mean serum ALT was 140 U/L. The subjects received Viread 300 mg or Hepsera 10 mg and were measured for complete response at 48 weeks. 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. This was observed in 71% of the subjects who received Viread compared to 49% of the subjects who received Hepsera. Histological Response was observed in 72% of the Viread group and 69% of the Hepsera group; HBV DNA reductions <400 copies/mL (<69 IU/mL) occurred in 93% and 63% of the Viread and Hepsera arms, respectively and normalized ALT was observed in 76% and 77% of the Viread and Hepsera arms, respectively.

HBeAg-Positive Chronic Hepatitis B
This randomized, double-blind, active-controlled study, dubbed Study 0103, enrolled 266 subjects with HBeAg+ nucleoside-naïve Hepatits B and compensated liver function. At baseline, subjects had a mean Knodell necroinflammatory score of 8.4; mean plasma HBV DNA was 8.7 log10 copies /mL; and mean serum ALT was 147 U/L. The subjects received Viread 300 mg or Hepsera 10 mg and evaluated for complete response at 48 weeks. Complete response was observed in 67% of the subjects who received Viread and 12% of the subjects who received Hepsera. Histological response was seen in 74% and 68% of the Viread and Hepsera arms, respectively; HBV DNA levels <400 copies/mL (<69 IU/mL) was observed in 76% of the Viread arm and 13% of the Hepsera arm and normalized ALT was reached in 68% and 54% of the Viread and Hepsera arms, respectively. In addition, HBeAg Loss/Seroconversion was seen in 20%/19% and 16%/16% of the Viread and Hepsera arms, respectively and HBsAg Loss/Seroconversion was seen in 3%/1% and 0/0 of the Viread and Hepsera arms, respectively.

Side Effects

Adverse events associated with the use of Viread may include (but are not limited to) the following:

•  
• Nausea
• Diarrhea
• Asthenia
• Headache
• Vomiting
• Flatulence

Adverse events associated with the use of Viread may include, but are not limited to, the following:

• nausea
• abdominal pain
• diarrhea
• headache
• dizziness
• fatigue
• nasopharyngitis
• back pain
• skin rash

Mechanism of Action

Viread is an HIV nucleotide analog reverse transcriptase inhibitor that helps block an enzyme crucial to the production and replication of HIV. Its active ingredient, tenofovir disoproxil fumarate, is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. In the body, this analog is converted to tenofovir, then is formed to tenofovir diphosphate by cellular enzymes. Lowering the amount of HIV in the blood, may in turn increase the number of T cells. This would improve the immune system, increasing its ability to defend the body against HIV infection.