Telbivudine

Usage

• Medical Conditions: Telbivudine is prescribed for the treatment of chronic hepatitis B (HBV) infection in adult patients with evidence of viral replication and either persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. It is important to note that telbivudine does not cure hepatitis B, but helps to control the viral replication.
• Pharmacological Classification: Nucleoside analogue reverse transcriptase inhibitor (NRTI), Antiviral agent.
• Mechanism of Action: Telbivudine inhibits HBV DNA polymerase (reverse transcriptase), blocking viral DNA replication. It is a synthetic thymidine nucleoside analogue that is phosphorylated intracellularly to its active triphosphate form. This active form competes with the natural substrate (thymidine 5’-triphosphate) for incorporation into viral DNA. The incorporation of telbivudine triphosphate into the viral DNA chain terminates further DNA synthesis, thus effectively halting viral replication.

Alternate Names

• International Nonproprietary Name (INN): Telbivudine
• Brand Name: Tyzeka (Note: Tyzeka has been discontinued in the US.)
• Other Names: Sebivo (EU)

How It Works

• Pharmacodynamics: Telbivudine exerts its antiviral effect by inhibiting HBV DNA polymerase. This leads to a reduction in HBV DNA levels in serum, indicating a decrease in viral load and replication.

• Pharmacokinetics:

  • Absorption: Telbivudine is well absorbed orally and can be taken with or without food. Its absorption and exposure are unaffected by a high-fat, high-calorie meal.
  • Metabolism: No metabolites of telbivudine have been detected in humans following administration.
  • Elimination: Primarily eliminated by renal excretion (~42% as unchanged drug). The terminal elimination half-life is 40-49 hours.

• Mode of Action: Telbivudine acts as a competitive inhibitor of HBV DNA polymerase by binding to the active site of the enzyme. This prevents the enzyme from incorporating natural nucleotides into the growing viral DNA chain.

• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Telbivudine functions as a viral DNA polymerase inhibitor. It does not significantly bind to other receptors or modulate neurotransmitters.

• Elimination Pathways: Primarily via renal excretion.

Dosage

Standard Dosage

Adults:

• 600 mg orally once daily, with or without food.

Children:

• Not recommended for use in children under 16 years of age.

Special Cases:

• Elderly Patients: No specific dose adjustment recommended for patients over 65 years of age, but consider renal function in elderly patients.
• Patients with Renal Impairment: Dose adjustment necessary for patients with creatinine clearance < 50 mL/min.
  • CrCl 30-49 mL/min: 600 mg every 48 hours.
  • CrCl < 30 mL/min (not requiring dialysis): 600 mg every 72 hours.
  • ESRD on hemodialysis: 600 mg every 96 hours (administer after hemodialysis).
• Patients with Hepatic Dysfunction: No dose adjustment necessary.
• Patients with Comorbid Conditions: Caution advised in patients with concomitant HIV infection.

Clinical Use Cases

Telbivudine is specifically indicated for chronic hepatitis B and doesn’t have a role in acute medical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations such as status epilepticus or cardiac arrest.

Dosage Adjustments

See above in “Special Cases”.

Side Effects

Common Side Effects

• Fatigue, headache, cough, diarrhea, abdominal pain, nausea, upper respiratory tract infection, arthralgia, myalgia, elevated creatine kinase, back pain, dizziness, insomnia.

Rare but Serious Side Effects

• Lactic acidosis, severe hepatomegaly with steatosis, peripheral neuropathy (especially with concomitant interferon alfa use), myopathy.

Long-Term Effects

• Potential for development of drug resistance with prolonged use.
• Risk of severe acute exacerbations of hepatitis B after discontinuation of therapy.

Adverse Drug Reactions (ADR)

• Lactic acidosis, severe hepatomegaly with steatosis, myopathy, peripheral neuropathy.

Contraindications

• Hypersensitivity to telbivudine.
• Concurrent use with pegylated interferon alfa-2a.

Drug Interactions

• Drugs affecting renal function (e.g., aminoglycosides, loop diuretics, platinum compounds, vancomycin, amphotericin B) may alter telbivudine plasma concentrations.
• Pegylated interferon alfa-2a increases the risk and severity of peripheral neuropathy.
• Other potential interactions exist. Consult a comprehensive drug interaction database for detailed information (e.g., drugs.com).

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B (US FDA). Shown to reduce the risk of mother-to-infant HBV transmission when given in combination with hepatitis B immune globulin and HBV vaccine to the newborn. Use only if clearly needed.
• Breastfeeding: An alternate agent may be preferred, particularly while breastfeeding newborn or preterm infants. Not studied in nursing mothers being treated for HBV infection.

Drug Profile Summary

• Mechanism of Action: HBV DNA polymerase inhibitor.
• Side Effects: Fatigue, headache, cough, diarrhea, nausea, lactic acidosis, severe hepatomegaly with steatosis, peripheral neuropathy, myopathy.
• Contraindications: Hypersensitivity, concurrent use with pegylated interferon alfa-2a.
• Drug Interactions: Drugs affecting renal function, pegylated interferon alfa-2a.
• Pregnancy & Breastfeeding: Category B; an alternate agent may be preferred during breastfeeding.
• Dosage: 600 mg orally once daily; dose adjustment in renal impairment.
• Monitoring Parameters: HBV DNA, ALT/AST, creatinine kinase, renal function tests.

Popular Combinations

Telbivudine is generally used as monotherapy. Combination with pegylated interferon alfa-2a is contraindicated.

Precautions

• General Precautions: Monitor renal function, especially in patients with pre-existing renal impairment. Monitor for signs and symptoms of lactic acidosis, hepatomegaly, myopathy, and peripheral neuropathy. Monitor for HBV resistance.
• Specific Populations: See “Dosage - Special Cases.”
• Lifestyle Considerations: No specific lifestyle considerations are generally associated with telbivudine use. However, counsel patients on the importance of adhering to their prescribed treatment regimen and avoiding behaviors that could worsen liver health (e.g., excessive alcohol consumption).

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Telbivudine?

A: The standard adult dose is 600mg orally once daily. Dose adjustments are necessary for patients with renal impairment. Refer to the ‘Dosage’ section above for more details.

Q2: How should I counsel patients on potential side effects of telbivudine?

A: Inform patients about the common side effects like fatigue, headache, cough, and gastrointestinal issues. Emphasize the importance of reporting any signs of muscle pain/weakness, numbness/tingling, or symptoms of liver problems promptly, as these could indicate rare but serious side effects.

Q3: What monitoring parameters are essential during telbivudine therapy?

A: Monitor HBV DNA levels, ALT/AST, creatinine kinase, and renal function tests regularly to assess treatment response, monitor for potential side effects, and detect drug resistance.

Q4: Is telbivudine safe in pregnancy?

A: Telbivudine is Pregnancy Category B. While animal studies haven’t shown fetal harm, it should be used during pregnancy only if clearly needed. It has been shown to reduce the risk of mother-to-infant HBV transmission when used in the second and/or third trimester along with hepatitis B immunoglobulin and HBV vaccine administered to the newborn. Discuss the risks and benefits with the patient.

Q5: Can telbivudine be used in patients with decompensated cirrhosis?

A: The safety and efficacy of telbivudine have not been established in patients with decompensated cirrhosis. Caution is advised in this patient population.

Q6: What is the role of telbivudine in the management of lamivudine-resistant HBV?

A: Telbivudine is not recommended for patients with established lamivudine-resistant HBV infection due to potential cross-resistance.

Q7: What is the recommended duration of telbivudine therapy?

A: The optimal duration of therapy is not established. Treatment decisions should be individualized based on factors such as HBeAg status, HBV DNA levels, ALT normalization, and the development of drug resistance.

Q8: Can telbivudine be combined with other antiviral agents for HBV?

A: The combination of telbivudine with pegylated or standard interferon alfa is contraindicated due to an increased risk of peripheral neuropathy. Other antiviral combinations should be used with caution and under specialist guidance.

Q9: How does renal impairment affect telbivudine dosing?

A: Telbivudine is primarily renally excreted, requiring dose adjustments in patients with renal impairment. Specific dosing recommendations are available in the ‘Dosage’ section. Ensure close monitoring of renal function and virologic response in these patients.