Entecavir Oral Tablet (Brand name: Baraclude)

is an antiviral medicine approved for the treatment of chronic hepatitis B virus (HBV) infections in certain adults and pediatric patients 2 years of age and older. Other common alternative therapies include drugs such as tenofovir alafenamide, tenofovir disoproxil fumarate [tenofovir DF]. Less common alternative therapies include drugs such as adefovir, lamivudine, telbivudine, interferon alfa, and peginterferon alfa.

Hepatitis B (HBV)

is a viral liver infection that can cause acute and/or chronic infections. Acute infections often do not require treatment and infrequently turn into a chronic disease. Chronic infections (6 months or more) can have long-term consequences on the liver including cirrhosis and liver cancer. Treatment of chronic HB is complicated, and usually should be managed by a specialist such as a gastroenterologist, hepatologist or an infectious disease specialist.

The American Association for the Study of Liver Diseases (AASLD, https://www.aasld.org) has published guidelines for management of HBV in 2016 (Terrault et al., AASLD Guidelines for Treatment of Chronic Hepatitis B, Hepatology. 2016 Jan;63(1):261-83) and an updated guidance in 2018 (Terrault et al., Update on prevention, diagnosis, and treatment of chronic1hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599). Additional information about treatment indications in patients with HBV are provided in the review paper by Fricker (Fricker et al., When (and When Not) to Treat Patients With HBV Infection, Clinical Gastroenterology and Hepatology 2019;17:2644–2647).

Definitions

• "ALT and AST" refers to liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that are indicators of liver damage or injury from different types of diseases or conditions.
• "anti-HBs" refers to antibody to hepatitis B surface antigen, indicative of recovery and immunity from HBV infection. It is also seen in people who have been successfully vaccinated against HBV.
• "anti-HBc" refers to antibody to hepatitis B core antigen, indicative of previous or ongoing HBV infection. It demonstrates recent or past exposure of the immune system to the hepatitis B virus and usually remains positive for life. To diagnose acute HBV, anti-HBc IgM antibody is used.
• "DNA" refers to Deoxyribonucleic Acid, a small molecule inside of cells that contain genetic information.
• "HBsAg" refers to hepatitis B surface antigen, indicative of HBV infection (can be acute or chronic).
• "Nucleoside analog" is a class of drugs used to treat viral infections that work by inhibiting the ability of the virus to replicate.

Medical Necessity Criteria for Initial Authorization

The Plan considers entecavir (Baraclude) medically necessary when ALL the following criteria are met for the applicable indication listed below:

Treatment of chronic hepatitis B virus infection

1. The requested medication is being prescribed by or in consultation with a gastroenterologist, hepatologist, or infectious disease specialist; AND
2. The member is 2 years of age or older; AND
3. The member has a documented diagnosis of chronic hepatitis B virus (HBV) infection with evidence (viral laboratory test results required) of active HBV replication and ONE (1) of the following:
   • a. persistent elevations in serum aminotransferase (ALT or AST) concentrations; or
   • b. histologic evidence of active liver disease in liver biopsy; or
   • c. histologic or radiographic evidence of liver cirrhosis; or
   • d. the member is pregnant, with HBV DNA > 200,000 IU/mL; AND
4. If the member is coinfected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV), the member meets ONE (1) of the following:
   • a. the member has hepatitis B and HIV coinfection AND is receiving a fully suppressive antiretroviral (ARV) treatment regimen for HIV; or
   • b. the member is coinfected with hepatitis B and chronic HCV and is currently receiving hepatitis C direct-acting antiviral (DAA) therapy; AND

Chart documentation and supporting laboratory test results are provided for review to substantiate the above listed requirements.

Hepatitis B virus reactivation prophylaxis

1. The requested medication is being prescribed by or in consultation with an oncologist, gastroenterologist, hepatologist, infectious disease, or transplant specialist; AND
2. The member is 2 years of age or older; AND
3. The requested medication is being used for prophylaxis against hepatitis B reactivation; AND
4. The member meets ONE of the following:
   • a. is anti-HBc-positive, HBsAg-positive AND receiving immunosuppressive or cytotoxic (e.g., anticancer) therapy; or
   • b. is anti-HBc-positive, HBsAg-negative AND undergoing stem cell transplantation or receiving anti-CD20 therapy, such as rituximab; or
   • c.is a non-liver solid organ transplant recipient of ONE (1) of the following:
     1. i. a HBsAg-positive extrahepatic organ; or
     2. ii. an anti-HBc-positive, HBsAg-negative organ; AND
5. If the member is coinfected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV), the member meets ONE (1) of the following:
   • a. the member has hepatitis B and HIV coinfection AND is receiving a fully suppressive antiretroviral (ARV) treatment regimen for HIV; or
   • b. the member is coinfected with hepatitis B and chronic HCV and is currently receiving hepatitis C direct-acting antiviral (DAA) therapy; AND
6. Chart documentation and supporting laboratory test results are provided for review to substantiate the above listed requirements.

Hepatitis B virus reinfection prophylaxis

1. The requested medication is being prescribed by or in consultation with a gastroenterologist, hepatologist, infectious disease, or transplant specialist; AND
2. The member is 2 years of age or older; AND
3. The requested medication is being used for prophylaxis of hepatitis B virus (HBV) reinfection; AND
4. The member has documentation of BOTH of the following:
   • a. history of chronic hepatitis B infection; and
   • b. liver transplant; AND
5. If the member is coinfected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV), the member meets ONE (1) of the following:
   • a. the member has hepatitis B and HIV coinfection AND is receiving a fully suppressive antiretroviral (ARV) treatment regimen for HIV; or
   • b. the member is coinfected with hepatitis B and chronic HCV and is currently receiving hepatitis C direct-acting antiviral (DAA) therapy; AND
6. Chart documentation and supporting laboratory test results are provided for review to substantiate the above listed requirements.

If the above prior authorization criteria are met, entecavir (Baraclude) will be approved for 12 months.

Medical Necessity Criteria for Reauthorization

Reauthorization for 12 months will be granted if BOTH of the following criteria are met:

1. the member still meets the applicable initial criteria; AND
2. recent (within the last 3 months) chart and laboratory test results documentation shows the member has experienced therapeutic response to the requested medication as evidenced by ONE (1) of the following:
   • a. a decrease or suppression of serum HBV DNA levels (viral load, reported in international units/mL or in copies/mL) compared to baseline (pre-treatment); or
   • b. a decrease or normalization of serum aminotransferase (ALT or AST) concentrations compared to baseline (pre-treatment); or
   • c. undetectable levels of serum HBV DNA or only minimal histologic evidence of liver injury

Experimental or Investigational / Not Medically Necessary

Entecavir (Baraclude) for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

References

1. Baraclude (entecavir) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; December 2018.
2. Chu M, Cho SM, Choe B, et al. Virologic responses to add-on adefovir dipivoxil treatment versus entecavir monotherapy in children with lamivudine-resistant chronic hepatitis B. J Pediatr Gastroenterol Nutr. 2012;55:648-652.

References

1. Baraclude (entecavir) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; December 2018.
2. Chu M, Cho SM, Choe B, et al. Virologic responses to add-on adefovir dipivoxil treatment versus entecavir monotherapy in children with lamivudine-resistant chronic hepatitis B. J Pediatr Gastroenterol Nutr. 2012;55:648-652.
3. Fricker, Z. P., & Reddy, K. R. (2019). When (and when not) to treat patients with HBV infection. Clinical Gastroenterology and Hepatology, 17(13), 2644-2647.
4. Fung J, Cheung C, Chan SC, et al. Entecavir monotherapy is effective in suppressing hepatitis B virus after liver transplantation. Gastroenterology. 2011;141(4):1212-1219.
5. Fung J, Wong T, Chok K, et al. Long-term outcomes of entecavir monotherapy for chronic hepatitis B after liver transplantation: results up to 8 years. Hepatology. 2017;66(4):1036-1044.
6. Huang H, Li X, Zhu J, et al. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA. 2014;312(23):2521-2530.
7. Li HR, Huang JJ, Guo HQ, et al. Comparison of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients during chemotherapy. J Viral Hepat. 2011;18(12):877-883.
8. Perrillo R, Buti M, Durand F, et al. Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B. Liver Transplant. 2013;19:887-895.
9. Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148(1):221-244.
10. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261-283. doi: 10.1002/hep.28156.
11. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599.
12. Yu S, Luo H, Pan M, et al. Comparison of entecavir and lamivudine in preventing HBV reactivation in lymphoma patients undergoing chemotherapy: a meta-analysis. Int J Clin Pharm. 2016;38(5):1035-1043.

Clinical Guideline Revision / History Information

Original Date: 11/05/2020

Reviewed/Revised: 10/14/2021, 12/01/2021, 9/15/2022, 9/21/2023