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Prior Authorization Protocol
TYZEKAR (telbivudine)


Coverage of drugs is first determined by the member’s pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:
    • The treatment of chronic hepatitis B in adult patients with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease
  2. Health Net Approved Indications and Usage Guidelines:
    Chronic hepatitis B (CHB)
    • Diagnosis of chronic hepatitis B virus infection
    • Failure or clinically significant adverse effects to Viread or Baraclude (new starts only)
  3. Coverage is Not Authorized For:
    • Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.
    • Combination therapy of Tyzeka and pegylated interferon alfa-2a
  4. General Information:
    • Combination of Tyzeka with pegylated interferon alfa-2a is contraindicated because of increased risk of peripheral neuropathy per the Tyzeka package insert
    • Patient co-infected with HIV should be evaluated by an HIV specialist to see if he/she needs to be treated with a HAART (highly active antiretroviral therapy) regimen that includes a component with activity against HBV (e.g. VireadR, EpivirR, or EmtrivaR).
    • According to the American Gastroenterological Association (AGA), recommendations on the treatment of chronic hepatitis B (CHB) are as follows:
      • HBV DNA results should be reported in IU/mL (1 IU/mL = 5.6 copies/mL)
      • The upper limits of normal for serum ALT concentrations for men and women are 30 IU/L and 19 IU/L, respectively.
      • Epivir-HBV is not recommended for first line use EXCEPT:
        • In patients receiving short-term antiviral prophylaxis during chemotherapy or in pregnancy, or
        • As part of an HIV regimen in patient with HBV/HIV co-infection, or
        • In combination with adefovir in patients with hepatic decompensation.
    • According to American Association for the Study of Liver Diseases (AASLD), recommendations for the treatment of CHB are:
      • In view of the high rate of drug resistance during long-term treatment, Epivir HBV or Tyzeka monotherapy are preferred only when used for a short course of treatment with the goal of seroconversion in HBeAg-positive patients.
      • Since Hepsera is less potent than other nucleos(t)ide analogue (NA) and is associated with increasing rate of antiviral resistance after the first year of therapy, it is best utilized as a second line drug in treatment-naive patients.
      • Hepatitis B treatment is recommended if HBV DNA level or ALT becomes higher from baseline in HBeAg-negative patients with initial HBV DNA levels of < 2,000 IU/mL and normal ALT.
      • Management of anti-viral resistant HBV should include monitoring of serum HBV DNA every 3-6 months during treatment.
    • Grading and staging a liver biopsy for patients with hepatitis B are as follows:
      • The grade is given a number based on the amount of inflammation (Knodell Scoring System).
        • 0 = no inflammation
        • 1-4 = minimal inflammation
        • 5-8 = mild inflammation
        • 9-12 = moderate inflammation
        • 13-18 = marked inflammation
      • The stage is scored based on the amount of fibrosis or scarring (Metavir Scoring System).
        • 0 = no scarring
        • 1 = minimal scarring
        • 2 = scarring has occurred and is outside the areas of the liver which include blood vessels
        • 3 = bridging fibrosis
        • 4 = cirrhosis or advanced scarring of the liver
    • Nonresponders may require a switch in treatment if the patient still has HBV DNA level more than 2,000 IU for HBeAg(-) and 20,000 for HBeAg(+) after one year of treatment. If the lack of response is due to drug resistance, pre-existing Tyzeka-resistant or Epivir-HBV-resistant mutations predispose to Baraclude resistance.
    • Cumulative rates of antiviral resistance in nucleos(t)ide-naive CHB patients are as follows:

    NucleoSIDE Analog
    NucleoTIDE Analog
    Epivir HBVR
    Drug Resistance
    (** Baraclude resistance reported within year 1 in patients with prior lamivudine resistance)
    ~20%, year 1
    ~70%, year 5
    ~25% up to year 2
    ~1% up to year 5 **
    None, year 1
    29%, year 5
    None, year 1
    na beyond 1 year

    • Prophylactic antiviral therapy is recommended for HBV carriers several weeks before or at the onset of cancer chemotherapy or a finite course of immunosuppressive therapy and maintained for 6 months afterwards. Antiviral prophylaxis is also considered for patients with HBsAg(+) undergoing therapy with anti-TNF agents (e.g. Remicade, Enbrel) for rheumatoid arthritis or inflammatory bowel disease. Epivir or Tyzeka can be used if the treatment is short (<12 months). Baraclude or Viread is preferred if longer duration of treatment is anticipated. Hepsera is a less suitable choice in the renal transplantation setting because of its risk of nephrotoxicity.
    • The risk of infection after transplantation of liver from HBsAg-negative, anti-HBc-positive donors has been reported to be as high as 75% and is related to the HBV immune status of the recipients. If anti-HBcpositive donor organs are used for HBV seronegative recipients, antiviral therapy should be administered to prevent de novo HBV infection. While the optimal duration of prophylactic therapy has not been determined, a limited duration such as 6-12 months may be sufficient for transplantation of non-hepatic solid organs. For transplantation of livers, life-long antiviral therapy is recommended, but whether HBIG is necessary is unclear.
    • Tyzeka resistant mutations are cross-resistant with Epivir.
    • For lamivudine-refractory patients, combination therapy of Epivir HBV and Hepsera or Viread has been shown effective in terms of virologic and biologic improvement. Adding Baraclude to Epivir lacks supporting data. Adding Tyzeka to Epivir is not more effective than Tyzeka alone.
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose
    Pegasys (peginterferon alfa 2a)*

    180 mcg SC q week as monotherapy

    180 mcg weekly for 48 weeks

    BaracludeTM (entecavir)

    Epivir-HBV -naive patients
    0.5 mg PO daily
    Dosage should be reduced in patients with renal impairment.
    Creatinine Clearance (mL/min): Dosing
    ≥ 50: 0.5 mg once daily
    30-49: 0.25 mg once daily or 0.5 mg every 48 hrs
    10-29: 0.15 mg once daily or 0.5 mg every 72 hrs
    <10, hemodialysis, continuous ambulatory peritoneal dialysis (CAPD): 0.05 mg once daily following hemodialysis or 0.5 mg every 7 days
    Patients with prior Epivir-HBV treatment or decompensated liver disease:
    1 mg PO daily
    Dosage should be reduced in patients with renal impairment.
    Creatinine Clearance (mL/min): Dosing
    ≥ 50: 1 mg once daily
    30-49: 0.5 mg once daily or 1 mg every 48 hrs
    10-29: 0.3 mg once daily or 1 mg every 72 hours
    <10, hemodialysis, CAPD: 0.1 mg once daily or 1 mg every 7 days following hemodialysis

    0.5 mg daily

    Viread* (tenofovir)

    300 mg PO daily
    Dosage should be reduced in patients with renal impairment.
    Creatinine Clearance (mL/min): Dosing
    ≥ 50: 300 mg once daily
    30-49: 300 mg every 48 hrs
    10-29: 300 mg every 72 to 96 hrs
    Hemodialysis: 300 mg every 7 days or after 12 hours of dialysis
    300 mg daily

    HepseraR (adefovir dipivoxil)

    10 mg PO daily
    Dosage should be reduced in patients with renal impairment.
    Creatinine Clearance (mL/min): Dosing
    > 50: 10 mg once daily
    30-49: 10 mg every 48 hrs
    10-29: 10 mg every 72 hrs
    Hemodialysis: 10 mg every 7 days following dialysis

    10 mg/day
    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit


    600 mg PO daily
    Dosage should be reduced in patients with renal impairment
    Creatinine Clearance (mL/min): Dosing
    > 50: 600 mg once daily
    30-49: 600 mg every 48 hrs or 400 mg once daily
    <30 (not on dialysis): 600 mg every 72 hrs or 200 mg once daily
    ESRD: 600 mg every 96 hrs after hemodialysis or 120 mg once daily after hemodialysis

    Length of Benefit

  7. Product Availability:
    Tyzeka: 600 mg tablet, 100 mg/5mL oral solution (300 mL bottle)
  8. References:
    1. Epivir HBV [Prescribing Information] Research Triangle Park, NC: GlaxoSmithKlineDecember 2013.
    2. Viread [Prescribing Information] Foster City, CA: Gilead Sciences;October 2013.
    3. Baraclude [Prescribing Information] Princeton, NJ: Bristol Myers Squibb Company;March 2014.
    4. Hepsera [Prescribing Information] Foster City, CA: Gilead Sciences; November 2012.
    5. Tyzeka [Prescribing Information] East Hanover, NJ: Novartis Pharmaceuticals Corp; January 2013.
    6. Pegasys [Prescribing Information] Hutley, NJ: Hoffmann-La Roche Inc; March 2015.
    7. Keeffe EB, Dieterich DT, Han SB, et al. A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2008 Update. Clin Gastroenterol Hepatol. 2008;6:1315-1341.
    8. Lok ASF, McMahon BJ. AASLD Practice Guidelines-Chronic Hepatitis B: Update 2009. Hepatology 2009; Vol. 50, No.3, 1-36.
    9. Dore GJ. The impact of HIV therapy on co-infection with hepatitis B and hepatitis C viruses. Curr Opin Infect Dis. 2001;14(6):749-755.
    10. Liaw YF. Management of YMDD mutations during lamivudine therapy in patients with chronic Hepatitis B. J Gastroenterol and Hepatol. 2002;17, S333-S337.
    11. Marcellin P, Lau GK, Bonino F, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Eng J Med. 2004; 351:1206-1217.
    12. Sung JJY, Lai YF, Zeuzem S, et al. A randomized, double-blind phase II study of lamivudine (LAM) compared to lamivudine plus adefovir dipivoxil (ADV) for the treatment of naove patients with chronic hepatitis B (CHB): week 52 analysis (abstr). J Hepatol. 2003;38:25.
    13. Ghany M, Lutchman G, Kleiner D, et al. Lamivudine and adefovir versus adefovir alone for HbeAg-positive chronic hepatitis B (abstr). Hepatology. 2005;42:591A-592A.
    14. Data on file, GlaxoSmithKline (NUC20912). Safety and efficacy of treatment with combination Epivir-HBV and Hepsera vs. Epivir-HBV alone in CHB patients.
    15. Sherman M, Yurdaydin C, Sollano J, et al. Entecavir is superior to continued lamivudine for the treatment of lamivudine-refractory HBeAg+ chronic hepatitis B: results of phase III study ETV-026 (abstr). Hepatology. 2004;40:664A.
    16. Gish R, Chang TT, Hadziyannis S, et al. Sustained viral load and ALT reduction following 48 weeks of entecavir treatment in HBeAg-negative and –positive patients with chronic hepatitis B who have failed prior lamivudine therapy [abstract]. J Hepatol. 2003;38(suppl 2):32.
    17. Lai CL, Rosmawati M, Lao J, et al. Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection. Gastroenterology. 2002;123:1831-1838.
    18. US National Institutes of Health. Entecavir plus tenofovir combination therapy versus entacavir monotherapy in naive subjects with chronic hepatitis B. Available at: Accessed June 4, 2015.
    19. US National Institutes of Health. Entecavir plus adefovir combination therapy versus entacavir monotherapy and adefovir monotherapy for chronic hepatitis B infected subjects. Available at:  Accessed June 4, 2015.
    20. MicromedexR Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically.  Accessed June 4, 2015.
    21. Clinical Pharmacology Web site. Available at:  Accessed June 4, 2015..
    22. American Hospital Formulary Service Drug Information Web site. Available at:  Accessed June 4, 2015.
The material provided to you are guidelines used by this plan to authorize, modify or determine coverage for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract.