Version May 2024
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.
Note: Tyzeka has been discontinued in the United States for more than 1 year.
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]).
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
No dosage adjustment necessary.
Note: Tyzeka has been discontinued in the US for more than 1 year.
Chronic hepatitis B: Oral: Adolescents ≥16 years: Refer to adult dosing.
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
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
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.
Tyzeka has been discontinued in the US for more than 1 year.
May be product dependent
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Sebivo: 600 mg [DSC]
May be administered without regard to food.
Oral: May be administered without regard to food.
Treatment of chronic hepatitis B with evidence of viral replication and either persistent transaminase elevations or histologically-active disease
None known.
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 Lexicomp 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 does not have a significant effect on telbivudine absorption. Management: Administer without regard to meals.
Treatment for hepatitis B should be evaluated prior to pregnancy. Telbivudine is not recommended for use in pregnant patients (AASLD [Terrault 2018]; EASL 2017).
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).
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.
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.
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.
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)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
