Nucleoside Reverse Transcriptase Inhibitors (NRTIs) for Chronic Hepatitis B

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

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 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 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, 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.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

Dizziness. It is more common when entecavir is used after lamivudine treatment. Feeling tired or weak. If you have any side effects. A fast heartbeat. Resistance is rare with entecavir. • • Side Effects NRTIs rarely have side effects. Adefovir and tenofovir may harm your kidneys if you are at risk for or have a kidney problem.8 Resistance to tenofovir has not been reported. they may include: • • • • • • • Fever. Resistance is less of a problem with adefovir. In rare cases. Tenofovir works better than adefovir against hepatitis B virus that is resistant to lamivudine. Feeling cold. less than one-third of HBV may be resistant to the medicine. Call your doctor if you develop any symptoms of these problems such as: • • • • • • Unusual muscle pain. Nausea. But resistance to telbivudine goes up greatly after one year of treatment. Headache. Belly pain. Pain in your belly or back. Resistance is less of a problem with telbivudine than with lamivudine. Dizziness. After 5 years of treatment. . up to 70% of HBV may be resistant to lamivudine. Diarrhea. NRTIs have led to severe liver problems or to a buildup of acid in the blood (lactic acidosis). Sore throat. But tenofovir is the newest NRTI approved to treat hepatitis B. up to one-third of hepatitis B viruses may be resistant to the medicine. After 5 years of adefovir treatment. especially when it is used as the first medicine to treat hepatitis B.• • • • After 1 year of treatment with lamivudine.

Lamivudine also costs less than interferons. and you may need to start taking the same or a different medicine again. Light-colored stools. See Drug Reference for a full list of side effects. If you are taking both telbivudine and peginterferon alfa-2a. Some NRTIs approved to treat HIV are being used to treat hepatitis B infections that have become resistant to lamivudine. 11 Treatment of hepatitis B with a combination of telbivudine and peginterferon alfa-2a increases the risk of nerve problems in your arms and legs (peripheral neuropathy).• • Yellowing of your skin or the whites of your eyes (jaundice). Telbivudine was approved by the FDA in 2006. 45(2): 507539. It also can be used for pregnant women if the benefits outweigh the risks. tell your doctor if you have any weakness or pain in an arm or leg. Adefovir may affect how well medicines for HIV work. entecavir.10. but you will end up taking it for a longer time than if you were taking interferons. These may affect how well your medicine for chronic hepatitis B works.) What To Think About • • • It is important to talk to your doctor about all the medicines and herbal remedies you are taking. so experts do not yet know the longterm effects of this medicine or how long it should be used. Hepatology. (Drug Reference is not available in all systems. • • • • • • • Complete the new medication information form (PDF) to help you understand this medication. NRTIs may get into breast milk and so are not thought to be safe for babies whose mothers are breast-feeding. McMahon BJ (2007). Studies have shown that telbivudine works better than lamivudine. your infection may come back (relapse). Lamivudine was the first NRTI approved to treat chronic hepatitis B. After treatment with any type of NRTI is stopped. Lamivudine costs less than adefovir and entecavir.9 But telbivudine is more expensive than lamivudine and may have similar problems with resistance. Citations 1. The studies have had different results about how well combining these medicines works compared to using only one medicine. There have been some studies combining lamivudine with peginterferon. Chronic hepatitis B. It is safe for people who have significant cirrhosis or who have a weakened immune system from another health problem. Lok ASF. adefovir. . or telbivudine.

Lai C-L. New England Journal of Medicine. (2005). Telbivudine versus lamivudine in patients with chronic hepatitis B. Reynaud L. A randomized. et al. 348(9): 800-807. SJ. 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. 2(2): 244-249. Tenofovir (TDF) has stronger antiviral effect than adefovir (ADV) against lamivudine (LAM)-resistant hepatitis B virus (HBV). (2006). 49(1): 72-79. et al. 9. et al. et al. controlled trial of combination therapy for chronic hepatitis B: Comparing pegylated interferon alfa-2b and lamivudine with lamivudine alone. (2009). Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. 8. Tenofovir and its potential in the treatment of hepatitis B virus. 352(26): 2673-2681.webmd. New England Journal of Medicine. 5(1): 177-185. H (2005). Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: A randomised trial. Janssen. et al. http://www. Lai C-L. (2009). 6. 357(25): 2576-2588. Hepatology International. Chang T-T. Leung N. Lancet. (2008). 354(10): 1001-1010. 5. (2005).com/hepatitis/nucleoside-reverse-transcriptase-inhibitorsnrtis-for-chronic-hepatitis-b#uf1284 . 3.2. et al. Annals of Internal Medicine. Hepatology. (2006). Hann H-W. New England Journal of Medicine. 4. 10. (2003). 365(9454): 123-129. 142(4): 240250. 7. Hadziyannis SJ. Entecavir versus lamivudine for patients with HBeAgnegative chronic hepatitis B. New England Journal of Medicine. 11. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. (2007). et al. 354(10): 1011-1020. Therapeutics and Clinical Risk Management. et al. New England Journal of Medicine. Chan HLY. et al. Hadziyannis.

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