Examples

Generic Name	Brand Name
adefovir	Hepsera
entecavir	Baraclude
lamivudine	Epivir-HBV
telbivudine	Tyzeka

How It Works

Nucleoside reverse transcriptase inhibitors (NRTIs) are medicines that slow the ability of the hepatitis B virus (HBV) to multiply in the body. They are taken as pills once a day for at least a year, and usually much longer. Entecavir is also available as a liquid that you swallow.

Adefovir, entecavir, and telbivudine are approved by the U.S. Food and Drug Administration (FDA) for use in adults. Lamivudine is approved for use by adults and by children ages 2 to 17.

Why It Is Used

NRTIs are used to treat long-term (chronic) HBV infection in adults and children who are at risk for liver disease. The American Association for the Study of Liver Disease has made recommendations on who should receive treatment for chronic hepatitis B based on the presence of hepatitis B antigens in your blood, the level of hepatitis B virus DNA (HBV DNA) in your blood, and the levels of your liver enzymes.¹

How Well It Works

Treatment for HBV infection is considered successful if blood tests show that the virus is no longer multiplying in the body, if liver enzyme levels return to normal, and if liver damage (such as inflammation and scarring) improves. NRTIs work in most of the people who take them, but relapse (the virus starts to multiply again) is common after a medicine is stopped, so you may have to take the medicine for a long time.^{1, 2}

The hepatitis B virus may develop resistance to some of the NRTIs:¹

• After 1 year of treatment with lamivudine, up to one-third of hepatitis B viruses may be resistant to the medicine. After 5 years of treatment, up to 70% of HBV may be resistant to lamivudine.
• Resistance is less of a problem with telbivudine than with lamivudine. But resistance to telbivudine goes up greatly after one year of treatment.
• Resistance is less of a problem with adefovir. After 5 years of adefovir treatment, less than one-third of HBV may be resistant to the medicine.
• Resistance is rare with entecavir, especially when it is used as the first medicine to treat hepatitis B. It is slightly more common when entecavir is used after lamivudine treatment.

Side Effects

NRTIs rarely have side effects. If you have any side effects, they may include:

• Fever.
• Feeling tired or weak.
• Headache.
• Sore throat.
• Diarrhea.
• Dizziness.
• Pain in your belly or back.

Adefovir may harm your kidneys if you are at risk for or have a kidney problem.

In rare cases, NRTIs have led to severe liver problems or to a buildup of acid in the blood (lactic acidosis). Call your doctor if you develop any symptoms of these problems such as:

• Unusual muscle pain.
• Belly pain.
• Nausea.
• Feeling cold.
• Dizziness.
• A fast heartbeat.
• Yellowing of your skin or the whites of your eyes (jaundice).
• Light-colored stools.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

• It is important to talk to your doctor about all the medicines and herbal remedies you are taking. These may affect how well your medicine for chronic hepatitis B works.
• After treatment with any type of NRTI is stopped, your infection may come back (relapse), and you may need to start taking the same or a different medicine again.
• Lamivudine was the first NRTI approved to treat chronic hepatitis B. It is safe for people who have significant cirrhosis or who have a weakened immune system from another health problem. It also can be used for pregnant women if the benefits outweigh the risks.
• The choice of NRTI depends upon how well it works, its safety, costs, and side effects:
  • Lamivudine costs less than adefovir and entecavir. Lamivudine also costs less than interferons, but you will end up taking it for a longer time than if you were taking interferons.
  • Some studies of entecavir show that it works better than lamivudine or adefovir.^{3, 4}
  • Lamivudine should be used for at least 1 year. If lamivudine is used for a long time, the hepatitis B virus may become resistant and no longer respond to the medicine.
  • Adefovir is effective against HBV infections that have become resistant to lamivudine, but adefovir costs more than lamivudine.¹ A study showed that treatment with adefovir worked better for some people with chronic hepatitis B if the medicine was taken for 144 weeks than if it was taken for only 48 weeks.⁵
  • Resistance is not as big a problem for adefovir and entecavir as it is for lamivudine.
  • Entecavir was approved by the U.S. Food and Drug Administration (FDA) in 2005, so experts do not yet know the long-term effects of this medicine or how long it should be used.
  • Telbivudine was approved by the FDA in 2006, so experts do not yet know the long-term effects of this medicine or how long it should be used. Studies have shown that telbivudine works better than lamivudine.⁶ But telbivudine is more expensive than lamivudine and may have similar problems with resistance.
• There have been some studies combining lamivudine with peginterferon. The studies have had different results about how well combining these medicines works compared to using only one medicine.^{7, 8}
• Adefovir may affect how well medicines for HIV work.
• NRTIs may get into breast milk and so are not thought to be safe for babies whose mothers are breast-feeding.
• Some NRTIs approved to treat HIV are being used to treat hepatitis B infections that have become resistant to lamivudine, adefovir, entecavir, or telbivudine.

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Citations

1. Lok ASF, McMahon BJ (2007). Chronic hepatitis B. Hepatology, 45(2): 507–539.

2. Hadziyannis SJ, et al. (2003). Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. New England Journal of Medicine, 348(9): 800–807.

3. Lai CL, et al. (2002) Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection. Gastroenterology, 123(6): 2135–2140.

4. de Man RA, et. al. (2001) Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection. Hepatology, 34(3): 578–82.

5. Hadziyannis, SJ, et al. (2005). Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. New England Journal of Medicine, 352(26): 2673–2681.

6. Lai C-L, et al. (2007). Telbivudine versus lamivudine in patients with chronic hepatitis B. New England Journal of Medicine, 357(25): 2576–2588.

7. Chan HLY, et al. (2005). A randomized, controlled trial of combination therapy for chronic hepatitis B: Comparing pegylated interferon alfa-2b and lamivudine with lamivudine alone. Annals of Internal Medicine, 142(4): 240–250.

8. Janssen, H (2005). Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: A randomised trial. Lancet, 365(9454): 123–129.