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Telbivudine (United States: Not available): Drug information

Telbivudine (United States: Not available): Drug information
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For additional information see "Telbivudine (United States: Not available): Patient drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Chronic hepatitis:

Severe, acute exacerbations of hepatitis B have been reported in patients who have discontinued anti–hepatitis B therapy, including telbivudine. Hepatic function should be closely monitored with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

Pharmacologic Category
  • Antihepadnaviral, Reverse Transcriptase Inhibitor, Nucleoside (Anti-HBV)
Dosing: Adult

Note: Tyzeka has been discontinued in the United States for more than 1 year.

Chronic hepatitis B

Chronic hepatitis B: Oral: 600 mg once daily.

Treatment duration (AASLD practice guidelines): Treatment duration for nucleos(t)ide analog-based therapy (eg, telbivudine) is variable and influenced by HBeAg status, duration of HBV suppression, and presence of cirrhosis/decompensation (AASLD [Terrault 2016]):

Patients without cirrhosis:

Hepatitis B e antigen (HBeAg) positive immune-active chronic hepatitis: Treat until HBeAg seroconversion; after seroconversion, prolonged duration of therapy is often required in patients treated with nucleos(t)ide analogues. Optimal duration is unknown; however, consolidation therapy is generally a minimum of 12 months of persistently normal ALT and undetectable serum HBV DNA levels after HBeAg seroconversion.

HBeAg-negative immune-active chronic hepatitis: Indefinite antiviral therapy is suggested unless there is competing rationale for discontinuation (risk/benefit decision); treatment discontinuation may be considered in patients with loss of HBsAg; however, there is insufficient evidence to guide decisions in these patients.

Patients with cirrhosis:

HBeAg-positive immune-active chronic hepatitis: In patients who seroconvert on therapy, continue antiviral therapy indefinitely due to concerns with decompensation and death, unless there is a strong competing rationale for discontinuation.

HBeAg-negative immune-active chronic hepatitis: Treatment discontinuation is not recommended due to potential for decompensation and death (limited data).

Viral breakthrough ( AASLD practice guidelines) : Patients with confirmed viral breakthrough (HBV DNA ≥100 units/mL with previously undetectable levels [<10 units/mL] or >1 log increase in HBV DNA) should either be switched to an alternative antiviral monotherapy agent with a high genetic barrier to resistance or receive a second antiviral agent with a complementary resistance profile; consult current clinical practice guidelines for recommended agents (AASLD [Terrault 2016]).

Dosing: Kidney Impairment: Adult

CrCl ≥50 mL/minute: No dosage adjustment is necessary.

CrCl 30-49 mL/minute: 600 mg every 48 hours

CrCl <30 mL/minute (not requiring dialysis): 600 mg every 72 hours

End-stage renal disease (ESRD): 600 mg every 96 hours

Hemodialysis: Administer after dialysis session

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

Note: Tyzeka has been discontinued in the US for more than 1 year.

Chronic hepatitis B

Chronic hepatitis B: Oral: Adolescents ≥16 years: Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Central nervous system: Fatigue (13%)

Neuromuscular & skeletal: Increased creatine phosphokinase (79%; grades 3/4: 16%, most asymptomatic and transient)

1% to 10%:

Central nervous system: Headache (10%), dizziness (4%), fever (4%), insomnia (3%)

Dermatologic: Skin rash (4%), pruritus (2%)

Endocrine & metabolic: Increased serum lipase (grades 3/4: 2%)

Gastrointestinal: Diarrhea (6%), abdominal pain (3% to 6%), nausea (5%), abdominal distension (3%), dyspepsia (3%)

Hematologic & oncologic: Neutropenia (grades 3/4: 2%)

Hepatic: Increased serum ALT (grades 3/4: 5% to 7%), increased serum AST (grades 3/4: 6%)

Infection: Exacerbation of hepatitis B (2%)

Neuromuscular & skeletal: Arthralgia (4%), back pain (4%), myalgia (3%)

Respiratory: Cough (6%), pharyngolaryngeal pain (5%)

<1%, postmarketing, and/or case reports: Hepatomegaly, hyperbilirubinemia, hypoesthesia, increased amylase, lactic acidosis, liver steatosis, myopathy, myositis, paresthesia, peripheral neuropathy, rhabdomyolysis, thrombocytopenia

Contraindications

Concurrent use with peginterferon alfa-2a.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to telbivudine or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases. Postmarketing cases of lactic acidosis were often associated with other conditions (rhabdomyolysis) and/or muscle-related events (eg, myopathy, myositis); some cases were also associated with pancreatitis, liver failure/hepatic steatosis, and renal failure. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).

• Myopathy/rhabdomyolysis: Myopathy, myositis, and rhabdomyolysis (including fatalities) have been reported; some cases have been associated with lactic acidosis. Myopathy (unexplained muscle aches and/or muscle weakness in conjunction with serum creatine kinase increases) may occur several weeks to months after initiation. Interrupt therapy if myopathy or rhabdomyolysis is suspected and discontinue therapy if myopathy or rhabdomyolysis is diagnosed. Patients taking concomitant medications associated with myopathy should be monitored closely.

• Peripheral neuropathy: May occur alone or in combination with pegylated interferon alfa-2a (concurrent use is contraindicated) or possibly other interferons. Symptoms have been observed within 3 months after initiation of therapy. Interrupt treatment for suspected peripheral neuropathy and discontinue if confirmed; symptoms may be reversible with discontinuation.

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Monitor liver function several months after stopping treatment; reinitiation of anti-hepatitis B therapy may be required.

• Human immunodeficiency virus: Telbivudine does not exhibit any clinically-relevant activity against HIV type 1.

• Renal impairment: Use caution in patients with moderate-to-severe renal dysfunction and ESRD; dosing adjustment required (CrCl <50 mL/minute).

Special populations:

• African-American or Hispanic patients: Safety and efficacy have not been established in Black/African-American or Hispanic patients.

• Coinfections: Safety and efficacy have not been studied in patients coinfected with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV).

• Liver transplant recipients: Safety and efficacy in liver transplant recipients have not been established; monitor renal function in patients receiving concurrent therapy of cyclosporine or tacrolimus.

Other warnings/precautions:

• Appropriate use: Current clinical hepatitis B practice guidelines do not recommend telbivudine for initial use in the management of chronic HBV due to high rates of developing resistance rapidly; other antiviral agents with a high genetic barrier to drug resistance are preferred (eg, tenofovir or entecavir) (AASLD [Terrault 2016]).

• Resistance: Cross-resistance among hepatitis B antivirals may develop; use caution in patients failing previous lamivudine therapy.

Product Availability

Tyzeka has been discontinued in the US for more than 1 year.

Generic Equivalent Available: US

May be product dependent

Pricing: US

Tablets (Tyzeka Oral)

600 mg (30): $1285.26

Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly.

Administration: Adult

May be administered without regard to food.

Administration: Pediatric

Oral: May be administered without regard to food.

Use: Labeled Indications

Treatment of chronic hepatitis B with evidence of viral replication and either persistent transaminase elevations or histologically-active disease

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination

Interferons (Alfa): May enhance the adverse/toxic effect of Telbivudine. Specifically, the risk of peripheral neuropathy may be increased. Risk C: Monitor therapy

Peginterferon Alfa-2a: May enhance the adverse/toxic effect of Telbivudine. Specifically, the risk for peripheral neuropathy may be increased. Risk X: Avoid combination

Food Interactions

Food does not have a significant effect on telbivudine absorption. Management: Administer without regard to meals.

Reproductive Considerations

Treatment for hepatitis B should be evaluated prior to pregnancy. Telbivudine is not recommended for use in pregnant patients (AASLD [Terrault 2018]; EASL 2017).

Pregnancy Considerations

Outcome data following maternal use of telbivudine during pregnancy are available (Deng 2020; Funk 2021; Jiang 2021; Li 2020; Li 2022; Nguyen 2022; Pan 2021; Ren 2020; Yi 2021; Zhu 2021). Agents other than telbivudine are recommended when hepatitis B treatment is needed in pregnant patients. Patients who become pregnant while taking telbivudine should be switched to the preferred agent (AASLD [Terrault 2018]; EASL 2017).

Data collection to monitor pregnancy and infant outcomes following exposure to telbivudine are ongoing. Health professionals are encouraged to enroll patients exposed to telbivudine in the antiretroviral pregnancy registry (1-800-258-4263).

Breastfeeding Considerations

It is not known if telbivudine is present in breast milk.

Patients requiring antivirals for hepatitis B may breastfeed if the infant received immunoprophylaxis at birth; however, recommendations are not specific to telbivudine, and other agents may be preferred (AASLD [Terrault 2018]; EASL 2017; SMFM [Dionne-Odom 2016]). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Manufacturer’s labeling: LFTs (eg, AST and ALT) periodically during therapy and for several months following discontinuation of therapy; renal function prior to initiation and periodically during treatment; signs and symptoms of peripheral neuropathy (eg, weakness, paresthesia, leg pain) or myopathy (eg, unexplained muscle pain, tenderness or weakness); serum creatine kinase.

Alternate recommendations: Chronic hepatitis B: HBV DNA and ALT (HBV DNA usually done every 3 months until undetectable and then every 3 to 6 months thereafter); HBeAg; anti-HBe (in patients who are HBeAg-positive to monitor for seroconversion); HBsAg; consider monitoring creatine kinase and lactic acidosis if symptoms are concerning; monitor for peripheral neuropathy; following discontinuation, monitor for recurrent viremia, ALT flares, seroreversion, and clinical decompensation every 3 months for at least 1 year (AASLD [Terrault 2016]). As antivirals do not eliminate the risk of hepatocellular carcinoma, continued monitoring for this complication is recommended in at-risk patients.

Mechanism of Action

Telbivudine, a synthetic thymidine nucleoside analogue (L-enantiomer of thymidine), is intracellularly phosphorylated to the active triphosphate form, which competes with the natural substrate, thymidine 5'-triphosphate, to inhibit hepatitis B viral DNA polymerase; enzyme inhibition blocks reverse transcriptase activity thereby reducing viral DNA replication.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vd: > total body water

Protein binding: ~3%

Metabolism: No metabolites detected

Half-life elimination: Terminal: 40-49 hours

Time to peak, plasma: 1-4 hours

Excretion: Urine (~42% as unchanged drug)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Sebivo;
  • (AU) Australia: Sebivo;
  • (BG) Bulgaria: Sebivo;
  • (BR) Brazil: Sebivo;
  • (CN) China: Su bi fu;
  • (DE) Germany: Sebivo;
  • (ES) Spain: Sebivo;
  • (FI) Finland: Sebivo;
  • (FR) France: Sebivo;
  • (GB) United Kingdom: Sebivo;
  • (GR) Greece: Sebivo;
  • (ID) Indonesia: Sebivo;
  • (IE) Ireland: Sebivo;
  • (IL) Israel: Sebivo;
  • (IN) India: Sebivo;
  • (KE) Kenya: Sebivo;
  • (KR) Korea, Republic of: Sebibo;
  • (KW) Kuwait: Sebivo;
  • (MA) Morocco: Sebivo;
  • (NL) Netherlands: Sebivo;
  • (NO) Norway: Sebivo;
  • (PH) Philippines: Sebivo;
  • (PK) Pakistan: Hepatel | Virokalim;
  • (PL) Poland: Sebivo;
  • (PY) Paraguay: Sebivo;
  • (RU) Russian Federation: Sebivo;
  • (SA) Saudi Arabia: Sebivo;
  • (SE) Sweden: Sebivo;
  • (SI) Slovenia: Sebivo;
  • (TH) Thailand: Sebivo;
  • (TR) Turkey: Sebivo;
  • (UA) Ukraine: Sebivo;
  • (UY) Uruguay: Sebivo;
  • (ZM) Zambia: Sebivo
  1. Deng H, Liang S, Xu M, et al. Clinical efficacy and safety in telbivudine- or tenofovir-treated hepatitis B e antigen-positive pregnant women. Antivir Ther. 2020;25(1):33-41. doi:10.3851/IMP3345 [PubMed 32049069]
  2. DHHS Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Department of Health and Human Services. November 2013. http://aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf.
  3. Dionne-Odom J, Tita AT, Silverman NS; Society for Maternal-Fetal Medicine (SMFM). SMFM Consult Series: #38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol. 2016;214(1):6-14. doi:10.1016/j.ajog.2015.09.100 [PubMed 26454123]
  4. European Association for the Study of the Liver (EASL). EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-398. doi:10.1016/j.jhep.2017.03.021 [PubMed 28427875]
  5. Funk AL, Lu Y, Yoshida K, et al. Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis. Lancet Infect Dis. 2021;21(1):70-84. doi:10.1016/S1473-3099(20)30586-7 [PubMed 32805200]
  6. Jiang H, Ye X, Chen C, Zhou G, Han G. Efficacy and long-term safety of telbivudine usage during second or third trimester in hepatitis B surface antigen positive mothers with high viral load: a 10-year prospective study. J Clin Gastroenterol. Published online October 11, 2022. doi:10.1097/MCG.0000000000001779 [PubMed 36227027]
  7. Kim JW, Park SH, Louie SG. Telbivudine: A Novel Nucleoside Analog for Chronic Hepatitis B. Ann Pharmacother. 2006;40(3):472-478. [PubMed 16507625]
  8. Li Z, Duan X, Hu Y, et al. Efficacy and safety of lamivudine or telbivudine in preventing mother-to-child transmission of hepatitis B virus: a real-world study. Biomed Res Int. 2020;2020:1374276. doi:10.1155/2020/1374276 [PubMed 32420317]
  9. Li Z, Xie B, Yi N, Cai H, Yi W, Gao X. Efficacy and safety of tenofovir disoproxil fumarate or telbivudine used throughout pregnancy for the prevention of mother-to-child transmission of hepatitis B virus: a cohort study. Eur J Obstet Gynecol Reprod Biol. 2022;276:102-106. doi:10.1016/j.ejogrb.2022.07.009 [PubMed 35853269]
  10. Liu M, Cai H, Yi W. Safety of Telbivudine Treatment for Chronic Hepatitis B for the Entire Pregnancy. J Viral Hepat. 2013;20(suppl 1):65-70. [PubMed 23458527]
  11. Nguyen HT, Thavorncharoensap M, Phung TL, et al. Comparative efficacy and safety of pharmacologic interventions to prevent mother-to-child transmission of hepatitis B virus: a systematic review and network meta-analysis. Am J Obstet Gynecol. 2022;227(2):163-172. doi:10.1016/j.ajog.2022.02.042 [PubMed 35263648]
  12. Pan CQ, Li MH, Zeng HH, et al. Developmental consequences of prenatal telbivudine exposure during the third trimester. Clin Gastroenterol Hepatol. 2021;19(5):1061-1063. doi:10.1016/j.cgh.2020.04.056 [PubMed 32371166]
  13. Ren C, Wang L, Sun W, Ma L, Dong Z, Hao A, Zhou L, Li F, Ma W. Efficacy and safety of telbivudine treatment for the prevention of HBV perinatal transmission. Medicine (Baltimore). 2020;99(24):e20583. doi:10.1097/MD.0000000000020583 [PubMed 32541488]
  14. Sebivo (telbivudine) [product monograph]. Dorval, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; June 2017.
  15. 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. doi:10.1002/hep.29800 [PubMed 29405329]
  16. 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 [PubMed 26566064]
  17. Tyzeka (telbivudine) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; December 2018.
  18. Yang H, Qi X, Sabagal A, et al. Cross-Resistance Testing of Next-Generation Nucleoside and Nucleotide Analogues Against Lamivudine-Resistant HBV. Antivir Ther. 2005;10(5):625-633. [PubMed 16152756]
  19. Yi W, Cao X, Zeng Z, et al. Developmental consequences of children born from mothers with telbivudine treatment during late pregnancy: a prospective study with 3-year follow-up. Virulence. 2021;12(1):1527-1537. doi:10.1080/21505594.2021 [PubMed 34120564]
  20. Zhu B, Lv X, Zhao Z, et al. Comparison of the efficacy and safety of tenofovir and telbivudine in interrupting mother-to-child transmission of hepatitis B virus. Medicine (Baltimore). 2021;100(44):e27695. doi:10.1097/MD.0000000000027695 [PubMed 34871254]
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