Telbivudine

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Telbivudine
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]

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Black Box Warning

WARNING
See full prescribing information for complete Boxed Warning.
LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS AND SEVERE ACUTE EXACERBATIONS OF HEPATITIS B:
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals.
Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including Tyzeka. Hepatic function should be monitored closely 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.

Overview

Telbivudine is a HBV nucleoside analogue reverse transcriptase inhibitor that is FDA approved for the {{{indicationType}}} 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. There is a Black Box Warning for this drug as shown here. Common adverse reactions include fatigue, increased creatine kinase (CK), headache, cough, diarrhea, abdominal pain, nausea, pharyngolaryngeal pain, arthralgia, pyrexia, rash, back pain, dizziness, myalgia, ALT increased, dyspepsia, insomnia, and abdominal distension.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Chronic Hepatitis B
  • Due to higher rates of resistance that may develop with longer term treatment among patients with incomplete viral suppression, treatment should only be initiated, if pre-treatment HBV DNA and ALT measurements are known, in the following patient populations:
  • For HBeAg-positive patients, HBV DNA should be less than 9 log10 copies per mL and ALT should be greater than or equal to 2x ULN prior to treatment with Tyzeka.
  • For HBeAg-negative patients, HBV DNA should be less than 7 log10 copies per mL prior to treatment with Tyzeka.
  • HBV DNA levels should be monitored at 24 weeks of treatment to assure complete viral suppression (HBV DNA less than 300 copies per mL). Alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment. Optimal therapy should be guided by further resistance testing.
  • The recommended dose of Tyzeka for the treatment of chronic hepatitis B is 600 mg once daily, taken orally, with or without food.
  • Tyzeka oral solution (30 mL) may be considered for patients who have difficulty with swallowing tablets.
  • Duration of Therapy
  • For patients with incomplete viral suppression (HBV DNA greater than or equal to 300 copies per mL) after 24 weeks of treatment, alternate therapy should be instituted. HBV DNA should be monitored every 6 months to assure continued response. If patients test positive for HBV DNA at any time after their initial response, alternate treatment should be instituted. Optimal therapy should be guided by resistance testing.
  • The optimal duration of therapy with Tyzeka for patients with chronic hepatitis B is unknown.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Telbivudine in adult patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Telbivudine in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Telbivudine in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Telbivudine in pediatric patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Telbivudine in pediatric patients.

Contraindications

Warnings

WARNING
See full prescribing information for complete Boxed Warning.
LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS AND SEVERE ACUTE EXACERBATIONS OF HEPATITIS B:
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals.
Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including Tyzeka. Hepatic function should be monitored closely 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.

Precautions

  • Lactic Acidosis
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals. Female gender, obesity, and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering HBV nucleoside analogue reverse transcriptase inhibitors to patients with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with Tyzeka should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
  • Exacerbations of Hepatitis B after Discontinuation of Treatment
  • Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including Tyzeka. Hepatic function should be monitored closely 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.
  • Myopathy
  • Cases of myopathy/myositis have been reported with Tyzeka use several weeks to months after starting therapy. Myopathy has also been reported with some other drugs in this class. Rhabdomyolysis has been reported during postmarketing use of Tyzeka.
  • Uncomplicated myalgia has been reported in Tyzeka-treated patients. Myopathy, defined as persistent unexplained muscle aches and/or muscle weakness in conjunction with increases in creatine kinase (CK) values, should be considered in any patient with diffuse myalgias, muscle tenderness, or muscle weakness. Among patients with Tyzeka-associated myopathy, no pattern with regard to the degree or timing of CK elevations has been observed. In addition, the predisposing factors for the development of myopathy among Tyzeka recipients are unknown. Patients should be advised to report promptly unexplained muscle aches, pain, tenderness, or weakness. Tyzeka therapy should be interrupted if myopathy is suspected, and discontinued if myopathy is confirmed. It is unknown whether the risk of myopathy during treatment with drugs in this class is increased with concurrent administration of other drugs associated with myopathy, including but not limited to: corticosteroids, chloroquine, hydroxychloroquine, certain HMGCoA reductase inhibitors, fibric acid derivatives, penicillamine, zidovudine, cyclosporine, erythromycin, niacin, and certain azole antifungals. Physicians initiating concomitant treatment with any drug associated with myopathy should monitor patients closely for any signs or symptoms of unexplained muscle pain, tenderness, or weakness.
  • Peripheral Neuropathy

Adverse Reactions

Clinical Trials Experience

  • Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
  • Assessment of adverse reactions is primarily based on two trials (007 GLOBE and NV-02B-015) in which 1,699 subjects with chronic hepatitis B received double-blind treatment with Tyzeka 600 mg per day (n=847 subjects) or lamivudine (n=852 subjects) for 104 weeks. The median duration of therapy was 104 weeks for both treatment groups.
  • In the 104 week clinical trials, most adverse experiences reported with Tyzeka were classified as mild or moderate in severity and were not attributed to Tyzeka. Selected adverse events of any severity which were reported in greater than or equal to 3% of Tyzeka and lamivudine recipients are shown in Table 2. With the exception of increased creatine kinase (CK), which was reported more frequently among Tyzeka recipients, the adverse event profile was similar for the two drugs.

T2

  • Moderate to severe (Grade 2-4) adverse events were reported in 239/847 (28%) of Tyzeka recipients and 229/852 (27%) of lamivudine recipients. The profile of adverse events of moderate to severe intensity was similar in both treatment groups and no individual adverse event was reported in greater than 2% of subjects in either treatment group.
  • Discontinuations due to adverse events were reported in 4% of Tyzeka recipients and 4% of lamivudine recipients. The most common adverse events resulting in Tyzeka discontinuation included increased CK, nausea, diarrhea, fatigue, myalgia, and myopathy.
  • Peripheral neuropathy was reported as an adverse event in less than 1% (2/847) of subjects receiving Tyzeka monotherapy [see Warnings and Precautions (5.4)]. Of Tyzeka-treated subjects less than 1% (5/847) were diagnosed with myopathy/myositis (presenting with muscular weakness).
  • Laboratory Abnormalities
  • Frequencies of selected treatment-emergent laboratory abnormalities in the 007 GLOBE and NV-02B-015 trials are listed in Table 3.

T3

  • Creatine Kinase (CK) Elevations
  • Creatine kinase (CK) elevations were more frequent among subjects on Tyzeka treatment. By 104 weeks of treatment, Grade 1-4 CK elevations occurred in 79% of Tyzeka-treated subjects and 47% of lamivudine-treated subjects. Grade 3 or 4 CK elevations occurred in 13% of Tyzeka-treated subjects and 4% of lamivudine-treated subjects. Most CK elevations were asymptomatic, but the mean recovery time was longer for subjects on Tyzeka than subjects on lamivudine.
  • Among Tyzeka-treated subjects with Grade 1-4 CK elevations, 10% developed a musculoskeletal adverse event compared to 5% of lamivudine-treated subjects. A total of 2% (13/847) Tyzeka-treated subjects interrupted or discontinued trial drug due to CK elevation or musculoskeletal adverse events1.
  • 1 Includes the Preferred Terms: back pain, chest wall pain, non-cardiac chest pain, chest discomfort, flank pain, muscle cramp, muscular weakness, musculoskeletal pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal stiffness, myalgia, myofascial pain syndrome, myopathy, myositis, neck pain, and pain in extremity.
  • ALT Flares During Treatment
  • The incidence of ALT flares, defined as ALT greater than 10 x ULN and greater than 2 x baseline, was similar in the two treatment arms (3%) in the first six months. After week 24, ALT flares were reported less frequently in the Tyzeka arm (2%) compared to the lamivudine arm (5%). Periodic monitoring of hepatic function is recommended during chronic hepatitis B treatment.
  • Exacerbations of Hepatitis after Discontinuation of Treatment
  • In the subset of subjects who discontinued treatment prematurely for reasons other than efficacy, or who elected not to continue Tyzeka in another clinical trial, 9/154 (6%) Tyzeka-treated and 10/180 (6%) lamivudine-treated subjects experienced an exacerbation of hepatitis (ALT elevation greater than 2 x baseline and greater than 10 x ULN) in the 4-month post-treatment period.
  • Results at 208 Weeks
  • After 104 weeks of blinded therapy in trials 007 GLOBE and NV-02B-015, 667 subjects received Tyzeka in an open-label extension trial, CLDT600A2303. Of those initially randomized to Tyzeka therapy, 78% of subjects (530/680) from trial 007 GLOBE and 82% (137/167) of subjects from trial NV-02B-015 enrolled into the extension trial and continued Tyzeka treatment for up to 208 weeks. The long-term Tyzeka safety population in trial CLDT600A2303 consisted of 655 subjects, including 518 subjects from trial 007 GLOBE and 137 subjects from trial NV-02B-015.
  • The overall safety profile from the pooled analysis up to 104 and 208 weeks was similar. Grade 3/4 CK elevations occurred in 16% of subjects (104/655) treated with Tyzeka in trial CLDT600A2303. Most grade 3/4 CK elevations were asymptomatic (74% of subjects without any muscle related adverse reaction) and transient (98% of episodes lasted one or two visits (visit interval 2 - 12 weeks) and 87% of subjects had one or two episodes). Most grade 3/4 CK elevations (93%) resolved spontaneously or returned to baseline levels. Two cases of myopathy and two cases of myositis were reported in the 655 Tyzeka-treated subjects.
  • Among the cohort of 655 subjects continuing Tyzeka for up to 208 weeks in trial CLDT600A2303, including the subgroup of patients (n=223) with mild renal impairment (eGFR 60-90 mL per min) at baseline, mean estimated GFR assessed by MDRD did not decline.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Telbivudine in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Drug Interactions

  • Drug
  • Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Telbivudine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Telbivudine during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Telbivudine with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Telbivudine with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Telbivudine with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Telbivudine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Telbivudine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Telbivudine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Telbivudine in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Telbivudine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Telbivudine in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Telbivudine in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Telbivudine in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Telbivudine in the drug label.

Pharmacology

There is limited information regarding Telbivudine Pharmacology in the drug label.

Mechanism of Action

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Telbivudine in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Telbivudine in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Telbivudine in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Telbivudine in the drug label.

How Supplied

Storage

There is limited information regarding Telbivudine Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Telbivudine in the drug label.

Precautions with Alcohol

  • Alcohol-Telbivudine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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