Telbivudine (Sebivo) is an antiviral medicine that inhibits the reverse transcriptase responsible for viral replication. It is used in the treatment of chronic active hepatitis B infection.

Telbivudine (sebivo) Uses:

• It is used in the treatment of chronic hepatitis B with evidence of viral replication and either persistent transaminase elevations or histologically-active disease.
• Other drugs to treat hepatitis B include interferon, lamvudine, tenofovir, and tenofovir alafnamide.

Telbivudine (sebivo) Dose in Adults

Telbivudine dose in the treatment of chronic hepatitis B:

• 600 mg orally once a day.

• Treatment duration (AASLD practice guidelines):

  • The Treatment duration for nucleoside/ nucleotide analog-based therapy like telbivudine is variable.
  • It is influenced by HBeAg status, duration of HBV suppression, and presence of cirrhosis/decompensation:

• Patients without cirrhosis:

  • Hepatitis B e antigen (HBeAg) positive immune-active chronic hepatitis:

    Treat until HBeAg seroconversion occurs
    • after seroconversion, a prolonged duration of therapy is mostly required in patients treated with nucleoside/ nucleotide analogs.
    • The optimal duration is unknown
    • however, consolidation therapy is generally a minimum of 1 year of persistently normal ALT and undetectable serum HBV DNA levels after HBeAg seroconversion.

  • HBeAg-negative immune-active chronic hepatitis:

    • Indefinite antiviral therapy is given unless there is a 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, give 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:

    • Discontinuation of treatment is not recommended because of the potential for decompensation and death

  • 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 changed to an alternative antiviral monotherapy agent with a high genetic barrier to resistance or receive a 2nd antiviral agent with a complementary resistance profile

Telbivudine (sebivo) Dose in Children

Telbivudine dose in the treatment of chronic Hepatitis B: 

• Adolescents ≥16 years:
  • Refer to adult dosing.

Telbivudine Pregnancy Risk Factor: B

• The AASLD chronic Hepatitis B treatment recommendations for hepatitis B-infected pregnant women (not co-infected with HIV) recommend antiviral therapy to lower the risk of perinatal transmission in HBV-positive pregnant women.
• Limited data are available on routine antiviral therapy to prevent perinatal transmission.
• Patients with viral loads greater than 200,000 units/ml might benefit from treatment.
• However, antiviral therapy is not recommended for patients with viral DNA less than 200,000 units/ml according to AASLD.

Telbivudine use during breastfeeding:

• It is unknown if breast milk contains telbivudine.
• Breastfeeding women with hepatitis B (not co-infected with HIV) should not be considered a contraindication.
• Antivirals are rarely excreted in breast milk and are unlikely to cause any significant toxicities.
• Mothers should inform their infants about the unknown risk of low-level infant exposure.
• This is in addition to the lack of long-term safety data for infants born to mothers who were exposed to antiviral agents during breastfeeding.
• According to the manufacturer breastfeeding during therapy should be considered in light of the risks to infants and the benefits to mothers.

Telbivudine Dose adjustment in patients with renal disease:

• CrCl ≥50 mL/minute:

  • No dosage adjustment is required.

• CrCl 30-49 mL/minute:

  • 600 mg every 48 hours given

• CrCl <30 mL/minute (not requiring dialysis):

  • 600 mg given every 72 hours

• End-stage renal disease (ESRD):

  • 600 mg given every 96 hours

• Hemodialysis:

  • Administer after the dialysis session

Telbivudine  Dose in Liver disease

• Adjustment in the dose is not required in patients with liver disease.

Common Side Effects of Telbivudine (Sebivo):

• Central nervous system:

  • Fatigue

• Neuromuscular & skeletal:

  • Increased creatine phosphokinase

Less Common Side Effects of Sebivo (Telbivudine):

• Central Nervous System:

  • Headache
  • Dizziness
  • Fever
  • Insomnia

• Dermatologic:

  • Skin Rash
  • Pruritus

• Endocrine & Metabolic:

  • Increased Serum Lipase

• Gastrointestinal:

  • Diarrhea
  • Abdominal Pain
  • Nausea
  • Abdominal Distension
  • Dyspepsia

• Hematologic & Oncologic:

  • Neutropenia

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST

• Infection:

  • Exacerbation Of Hepatitis B

• Neuromuscular & Skeletal:

  • Arthralgia
  • Back Pain
  • Myalgia

• Respiratory:

  • Cough
  • Pharyngolaryngeal Pain

Contraindications to Telbivudine (sebivo):

• Concurrent use of peginterferon alfa-2a
• Hypersensitivity to telbivudine and any part of its formulation

Warnings and precautions

• Lactic acidosis/ hepatomegaly:

  • With nucleoside analogs, severe hepatomegaly and steatosis with lactic acidosis have been reported. Some cases even proved fatal.
  • Many cases of postmarketing lactic acidosis were associated with other conditions (rhabdomyolysis and/or muscle-related events (eg myopathy, myositis); some cases were also seen in the context of pancreatitis/hepatic Steasis and renal failure.
  • Patients who have clinical or laboratory evidence of lactic acidosis or hepatotoxicity should not be treated.

• Myopathy/rhabdomyolysis:

  • There have been reports of myopathy, myositis, and rhabdomyolysis, some with lactic acidosis.
  • Myopathy may be undiagnosed for several weeks or months after its initiation.
  • It is caused by undiagnosed muscle aches or weakness, in combination with serum creatine Kinase increases.
  • If myopathy or Rhabdomyolysis is suspected, interrupt therapy and stop therapy if it is confirmed.
  • Patients who take concomitant medication for myopathy should be closely monitored.

• Peripheral neuropathy:

  • Peripheral neuropathy may occur either alone or with the combination of pegylated Interferon Alfa-2a (concurrent usage is contraindicated), or other interferons.
  • Within three months of the therapy's initiation, symptoms were evident.
  • Stop treatment of suspected peripheral neuropathy. If confirmed, symptoms can be reversed by discontinuing.

• Chronic Hepatitis B: [US-Boxed Warning]

  • After discontinuation of treatment. An acute exacerbation may occur if hepatitis B is severe.
  • After stopping treatment, monitor liver function for several months. Restarting anti-hepatitis B therapy might be necessary.

• Human immunodeficiency virus:

  • Telbivudine has no clinically relevant activity against HIV type 1.

• Renal impairment

  • Patients with severe renal dysfunction or ESRD should be cautious. Dosing adjustments are required (CrCl 50 mL/minute).

Telbivudine (United States: Not available): Drug Interaction

Monitor:

• Liver function tests (eg, AST and ALT) should be checked periodically during therapy and for several months after the discontinuation of therapy
• renal function before 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.

• Chronic hepatitis B:

  • HBV DNA and ALT are usually done every three months until undetectable and then every 3 - 6 months thereafter
  • HBeAg
  • Monito for seroconversion (anti-HBe positivity in patients who are HBeAg positive)
  • HBsAg
  • consider monitoring creatine kinase and lactic acidosis if symptoms are concerning
  • monitor for peripheral neuropathy
  • following stopping, monitor for recurrent viremia, ALT flares, seroreversion, and clinical decompensation every 3 months for at least 1 year
  • Monito periodically for hepatocellular carcinoma especially in patients at high risk.

How to administer Telbivudine (Sebivo)?

• May be administered without regard to food.

Mechanism of action of Telbivudine (Sebivo):

• Telbivudine (L-enantiomer thymidine) is a synthetic thymidine nucleoside analog.
• It is phosphorylated intracellularly into the active triphosphate version, which competes against the natural substrate, thymidine 5-'-triphosphate to inhibit hepatitis A viral DNA polymerase
• It blocks the enzyme and inhibits reverse transcriptase activity, resulting in the inhibition of viral DNA replication.

Distribution: V :

• > 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:  

• Via Urine (~42% as unchanged drug)

International Brands of Telbivudine:

• Ramenart
• Sebivo
• Telbihep

Telbivudine Brand Names in Pakistan: