DESCRIPTION
Seven pharmaceutical agents are approved for the treatment of chronic hepatitis B (CHB) in the United States. Two agents are recombinant products of naturally occurring proteins, the interferons, which have both antiviral and immunomodulating properties. One interferon product is pegylated, a process by which a molecule of polyethylene glycol is joined to the active interferon molecule enabling the interferon to remain active longer in the body. The other five agents are analogs of nucleosides or nucleotides, basic components of RNA and DNA. These agents inhibit a critical step of the hepatitis B virus (HBV) life cycle by preventing the conversion of viral RNA to DNA.
Examples of preparations of recombinant interferons for the treatment of chronic hepatitis B are interferon alfa-2b (Intron® A) and peginterferon alfa-2a (Pegasys®).
Examples of preparations of nucleosides or nucleotides for the treatment of chronic hepatitis B are adefovir dipivoxil (Hepsera®), entecavir (Baraclude®), lamivudine (EpiVir® HBV), telbuvidine (Tyzeka®) and tenofovir disoproxil fumarate (Viread®).
REFER TO DECISION SUPPORT TREE
POLICY
Pharmaceutical management of chronic hepatitis B (CHB) is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
MEDICAL APPROPRIATENESS
Pharmaceutical management of chronic hepatitis B (CHB) is considered medically appropriate if ALL of the following criteria are met:
Individual has been positive for the hepatitis B surface antigen (HBsAg-positive) for at least six months
Individual has indication of active viral replication with HBV DNA levels at ANY ONE of the following:
Greater than 20,000 IU/mL for hepatitis B e-antigen positive (HBeAg-positive) disease
2,000 IU/mL or greater for HBeAg-negative disease
Compensated liver function (as required for treatment with specific agents) is evidenced by ALL of the following:
Absence of hepatic encephalopathy, variceal bleeding, ascites and other signs of clinical decompensation
Normal bilirubin levels
Albumin levels stable and within normal limits
Prothrombin times of ANY ONE of the following:
Individuals 18 years of age or older, less than 3 seconds prolonged
Individuals 1 to 17 years of age, less than or equal to 2 seconds prolonged
White blood cell counts greater than or equal to 4000/mm3
Platelet counts of ANY ONE of the following:
For individuals 18 years of age or older, greater than or equal to 100,000/mm3
For individuals 1 to 17 years of age, greater than or equal to 150,000/mm3
Treatment is with ANY ONE of the following agents:
Interferon alfa-2b if ALL of the following criteria are met:
Individual is one year of age or older
CBC and platelet counts are monitored during treatment
Individual has elevated levels of alanine aminotransferase (ALT) greater than 2 times normal
Liver function is compensated
Peginterferon alfa-2a if ALL of the following criteria are met:
Individual is 18 years of age or older
Individual has elevated levels of alanine aminotransferase (ALT) greater than 2 times normal
Liver function is compensated
Adefovir dipivoxil if ANY ONE of the following criteria are met:
Individual is 12 years of age to less than 18 years of age with ALL of the following:
HBeAg-positive
Compensated liver function
Evidence of ANY ONE of the following:
Elevated levels of alanine aminotransferase (ALT) greater than 2 times normal
Histologically active disease
Individual is 18 years of age or older with ALL of the following:
Compensated liver function
Evidence of ANY ONE of the following:
Elevated levels of alanine aminotransferase (ALT) greater than 2 times normal
Histologically active disease
Individual is 18 years of age or older with ALL of the following:
Clinical evidence of lamivudine-resistant disease with ANY ONE of the following:
Compensated liver function
Decompensated liver function
Evidence of ANY ONE of the following:
Elevated levels of alanine aminotransferase (ALT) greater than 2 times normal
Histologically active disease
Entecavir if ALL of the following criteria are met:
Individual is 18 years of age or older
Individual has evidence of ANY ONE of the following:
Elevated levels of alanine aminotransferase (ALT) greater than 2 times normal
Histologically active disease
Liver function is ANY ONE of the following:
Compensated
Decompensated
Lamivudine if ALL of the following criteria are met:
Individual is 2 years of age or older
Individual is HBeAg-positive
Individual has evidence of ANY ONE of the following:
Elevated levels of alanine aminotransferase (ALT) greater than 2 times normal
Histologically active disease
Liver function is compensated
Telbivudine if ALL of the following criteria are met:
Individual is 16 years of age or older
Individual has evidence of ANY ONE of the following:
Elevated levels of alanine aminotransferase (ALT) greater than 2 times normal
Histologically active disease
Liver function is compensated
Tenofovir disoproxil fumarate if ALL of the following criteria are met:
Individual is 18 years of age or older
Liver function is compensated
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
HBV DNA assay is a direct measure of viral load. PCR-based assays (those assays based on polymerase chain reaction technology) are standards for the measurement of HBV DNA. The World Health Organization (WHO) has established an international standard for hepatitis B quantification units in which one international unit (IU) is equal to about five genome equivalents.
No controlled studies were found in the published literature that validate the use of other interferons, pegylated interferons or analogs of nucleosides or nucleotides in the treatment of chronic hepatitis B.
SOURCES
American Association for the Study of Liver Disease. (2009, September). Chronic hepatitis B: update 2009. Retrieved August 17, 2010 from http://www.guideline.gov/content.aspx?id=15475&search=chronic+hepatitis+b.
Genentech, Inc. (2010, June). Pegasys® (peginterferon alfa-2a). Retrieved August 17, 2010 from (http://www.gene.com/gene/products/information/pegasys/pdf/pi.pdf.
Lexi-Comp Online. (2010). AHFS DI. Adefovir dipivoxil. Retrieved August 17, 2010 from Lexi-Comp Online with AHFS.
Lexi-Comp Online. (2010). AHFS DI. Entecavir. Retrieved August 17, 2010 from Lexi-Comp Online with AHFS.
Lexi-Comp Online. (2010). AHFS DI. Interferon alfa (antiviral). Retrieved August 17, 2010 from Lexi-Comp Online with AHFS.
Lexi-Comp Online. (2010). AHFS DI. Lamivudine. Retrieved August 17, 2010 from Lexi-Comp Online with AHFS.
Lexi-Comp Online. (2010). AHFS DI. Peginterferon alfa. Retrieved August 17, 2010 from Lexi-Comp Online with AHFS.
Lexi-Comp Online. (2010). AHFS DI. Telbivudine. Retrieved August 17, 2010 from Lexi-Comp Online with AHFS.
Lexi-Comp Online. (2010). AHFS DI. Tenofovir disoproxil fumarate. Retrieved August 17, 2010 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2010). Adefovir dipivoxil. Retrieved August 17, 2010 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2010). Entecavir. Retrieved August 17, 2010 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2010). Interferon alfa-2b. Retrieved August 17, 2010 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2010). Lamivudine. Retrieved August 17, 2010 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2010). Peginterferon alfa-2a. Retrieved August 17, 2010 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2010). Telbivudine. Retrieved August 17, 2010 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2010). Tenofovir disoproxil fumarate. Retrieved August 17, 2010 from MICROMEDEX Healthcare Series.
Schering-Plough. (2009, August). Intron® A (interferon alfa-2b, recombinant) for injection product information. Retrieved August 17, 2010 from http://www.introna.com/introna/home.action.
U. S. Food and Drug Administration. (2007, September). Center for Drug Evaluation and Research. Epivir®-HPV (lamivudine). Retrieved August 17, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021003s010,021004s010lbl.pdf.
U. S. Food and Drug Administration. (2009, July). Center for Drug Evaluation and Research. Baraclude® (entecavir) tablets. Retrieved November 8, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021797s010,021798s011lbl.pdf.
U. S. Food and Drug Administration. (2009, October). Center for Drug Evaluation and Research. Hepsera® (adefovir dipivoxil) tablets. Retrieved August 17, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021449s016lbl.pdf.
U. S. Food and Drug Administration. (2010, March). Center for Drug Evaluation and Research. Tyzeka® (telbivudine). Retrieved August 17, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022011s003,022154s001lbl.pdf.
U. S. Food and Drug Administration. (2010, March). Center for Drug Evaluation and Research. Viread® (tenofovir disoproxil fumarate) tablets. Retrieved August 17, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021356s033lbl.pdf.
ORIGINAL EFFECTIVE DATE: 3/14/2008
MOST RECENT REVIEW DATE: 10/6/2010
ID_BT
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
Pharmaceutical Decision Support Tree
Pharmaceutical Management of Chronic Hepatitis B
If yes, go to question #2
If no, this does not meet medical necessity and/or medical appropriateness criteria
Has the individual tested positive for hepatitis B surface antigen (HBsAg-positive) for at least six months?
If yes, go to question #3
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual show evidence of active viral replication with HBV DNA levels at greater than 20,000 IU/mL for HBeAg-positive disease or 2,000 IU/mL or greater for HBeAg-negative disease?
If yes, go to question #4
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual show that liver function is compensated as evidenced by ALL of the following?
Absence of hepatic encephalopathy, variceal bleeding, ascites and other signs of clinical decompensation
Normal bilirubin levels
Albumin levels stable and within normal limits
Prothrombin times of ANY ONE of the following:
Individuals 18 years of age or older, prolonged less than 3 seconds
Individuals 1 to 17 years of age, prolonged less than or equal to 2 seconds
White blood cell counts greater than or equal to 4000/mm3
Platelet counts of ANY ONE of the following:
For individuals 18 years of age or older, greater than or equal to 100,000/mm3
For individuals 1 to 17 years of age, greater than or equal to 150,000/mm3
If yes, go to question #5
If no, go to question #21
Is the requested agent interferon alfa-2b (Intron A®)?
If yes, go to question #6
If no, go to question #7
Does the individual show evidence of ALL of the following?
Individual is one year of age or older
CBC and platelet counts are to be monitored during treatment
Elevated level of serum alanine aminotransferase (ALT)
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is the requested agent peginterferon alfa-2a (Pegasys®)?
If yes, go to question #8
If no, go to question #9
Is the individual 18 years of age or older with persistent elevations in serum aminotransferases (ALT/AST)?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is the requested agent entecavir (Baraclude®)?
If yes, go to question #10
If no, go to question #11
Is the individual 18 years of age or older with persistent elevations in serum aminotransferases (ALT/AST) or histologically active disease?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is the requested agent lamivudine (EpiVir® HBV)?
If yes, go to question #12
If no, go to question #13
Is the individual 2 years of age or older with HBeAg-positive disease and persistent elevations in serum aminotransferases (ALT/AST) or histologically active disease?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is the requested agent telbuvidine (Tyzeka®)?
If yes, go to question #14
If no, go to question #15
Is the individual 16 years of age or older with persistent elevations in serum aminotransferases (ALT/AST) or histologically active disease?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is the requested agent tenofovir disoproxil fumarate (Viread®)?
If yes, go to question #16
If no, go to question #17
Is the individual 18 years of age or older?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is the requested agent adefovir dipivoxil (Hepsera®)?
If yes, go to question #18
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual show evidence of persistent elevations in serum aminotransferases (ALT/AST) or histologically active disease?
If yes, go to question #19
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is the individual 12 years of age to less than 18 years of age with HBeAg-positive disease?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #20
Is the individual 18 years of age or older?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual show evidence of ALL of the following?
Individual is 18 years of age or older
Persistent elevations in serum aminotransferases (ALT/AST) or histologically active disease
If yes, go to question #22
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual show clinical evidence of lamivudine-resistant disease and the requested agent is adefovir dipivoxil (Hepsera®)?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #23
Is the requested agent entecavir (Baraclude®)?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.