Nucleoside Reverse Transcriptase Inhibitors (NRTIs) for Chronic Hepatitis B

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Nucleoside Reverse Transcriptase Inhibitors (NRTIs) for Chronic Hepatitis B


Generic NameBrand Name

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, telbivudine, and tenofovir 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 the liver enzyme alanine aminotransferase (ALT).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

Some studies of entecavir show that it works better than lamivudine or adefovir.3, 4, 5

Adefovir is effective against HBV infections that have become resistant to 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.6

Tenofovir is effective at reducing the amount of hepatitis B virus in the body.7

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, about one-fifth (20%) of HBV was resistant to the medicine.
  • Resistance is rare with entecavir, especially when it is used as the first medicine to treat hepatitis B. It is more common when entecavir is used after lamivudine treatment.
  • Tenofovir works better than adefovir against hepatitis B virus that is resistant to lamivudine.8
  • Not many studies about resistance to tenofovir have been reported..

Side Effects

All medicines have side effects. But many people don't feel the side effects, or they are able to deal with them. Ask your pharmacist about the side effects of each medicine you take. Side effects are also listed in the information that comes with your medicine.

Here are some important things to think about:

  • Usually the benefits of the medicine are more important than any minor side effects.
  • Side effects may go away after you take the medicine for a while.
  • If side effects still bother you and you wonder if you should keep taking the medicine, call your doctor. He or she may be able to lower your dose or change your medicine. Do not suddenly quit taking your medicine unless your doctor tells you to.

Call 911 or other emergency services right away if you have:

  • Trouble breathing.
  • Swelling of your face, lips, tongue, or throat.

Call your doctor if you:

  • Have belly pain or unusual muscle pain.
  • Have weakness or pain in an arm or leg.
  • Feel sick to your stomach or feel unusually cold.
  • Feel dizzy or have a fast heartbeat.
  • Notice yellowing of your skin or the whites of your eyes (jaundice).
  • Develop hives.

Common side effects of these medicines include:

  • Fever.
  • Feeling tired or weak.
  • Headache.
  • Sore throat.
  • Diarrhea.

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

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.

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.9, 10

Adefovir may affect how well medicines for HIV work.

Taking medicine

Medicine is one of the many tools your doctor has to treat a health problem. Taking medicine as your doctor suggests will improve your health and may prevent future problems. If you don't take your medicines properly, you may be putting your health (and perhaps your life) at risk.

There are many reasons why people have trouble taking their medicine. But in most cases, there is something you can do. For suggestions on how to work around common problems, see the topic Taking Medicines as Prescribed.

Advice for women

If you are pregnant, breast-feeding, or planning to get pregnant, do not use any medicines unless your doctor tells you to. Some medicines can harm your baby. This includes prescription and over-the-counter medicines, vitamins, herbs, and supplements. And make sure that all your doctors know that you are pregnant, breast-feeding, or planning to get pregnant.


Follow-up care is a key part of your treatment and safety. Be sure to make and go to all appointments, and call your doctor if you are having problems. It's also a good idea to know your test results and keep a list of the medicines you take.

Complete the new medication information form (PDF)(What is a PDF document?) to help you understand this medication.



  1. Lok SFL, McMahon BJ (2009). Chronic Hepatitis B: Update 2009. Available online:
  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. Chang T-T, et al. (2006). A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. New England Journal of Medicine, 354(10): 1001–1010.
  4. Lai C-L, et al. (2006). Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. New England Journal of Medicine, 354(10): 1011–1020.
  5. Leung N, et al. (2009). Early hepatitis B virus DNA reduction in hepatitis B e antigen-positive patients with chronic hepatitis B: A randomized international study of entecavir versus adefovir. Hepatology, 49(1): 72–79.
  6. 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.
  7. Reynaud L, et al. (2009). Tenofovir and its potential in the treatment of hepatitis B virus. Therapeutics and Clinical Risk Management, 5(1): 177–185.
  8. Hann H-W, et al. (2008). Tenofovir (TDF) has stronger antiviral effect than adefovir (ADV) against lamivudine (LAM)-resistant hepatitis B virus (HBV). Hepatology International, 2(2): 244–249.
  9. 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.
  10. 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.


ByHealthwise Staff
Primary Medical ReviewerKathleen Romito, MD - Family Medicine
Specialist Medical ReviewerW. Thomas London, MD - Hepatology
Last RevisedOctober 29, 2012

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