Sebivo600 mg

Sebivo is a nucleoside analogue antiviral medicine approved for the treatment of chronic hepatitis B virus (HBV) infection in adults.

Established/FDA-approved use

• Treatment of chronic hepatitis B in adults with evidence of active viral replication (detectable HBV DNA) and either persistently elevated serum aminotransferases (ALT or AST) or histologically active liver disease on biopsy.

Sebivo is used to suppress HBV replication and improve liver histology; it is not a cure and does not eliminate the virus from the body.

Note: Sebivo is not indicated for infection with HIV, hepatitis C, or hepatitis A, and is not used for post-exposure prophylaxis.

Each film-coated tablet contains Telbivudine 600 mg as the active ingredient. An oral solution formulation containing Telbivudine 100 mg/5 mL may also be available in some markets.

Sebivo is a synthetic thymidine nucleoside analogue with selective activity against hepatitis B virus (HBV). It works by being incorporated into viral DNA after intracellular phosphorylation, thereby inhibiting HBV DNA polymerase (reverse transcriptase) activity and halting viral replication. Sebivo is administered orally, generally as a once-daily 600 mg tablet, for the long-term management of chronic hepatitis B infection in adults.

Sebivo belongs to the class of antiviral agents known as nucleoside reverse transcriptase inhibitors (specifically an L-nucleoside analogue), used in the management of chronic hepatitis B virus infection.

Mechanism of Action

Telbivudine is phosphorylated intracellularly by cellular kinases to its active triphosphate form. This triphosphate competes with the natural substrate thymidine 5'-triphosphate for incorporation into viral DNA by HBV DNA polymerase. Once incorporated, it causes DNA chain termination, thereby inhibiting HBV DNA synthesis.

Pharmacokinetics

• Absorption: Well absorbed orally; food does not significantly affect exposure.
• Distribution: Low plasma protein binding (approximately 3.3%).
• Metabolism: Not significantly metabolized by cytochrome P450 enzymes.
• Elimination: Primarily eliminated unchanged in urine via renal excretion; terminal half-life is approximately 40-49 hours.

Sebivo tablets should be swallowed whole with water, once daily, at approximately the same time each day, with or without food. If a dose of Sebivo is missed, it should be taken as soon as remembered unless it is almost time for the next dose, in which case the missed dose should be skipped - do not double the dose.

Pegylated Interferon alfa-2a

Co-administration of Sebivo with pegylated interferon alfa-2a increases the risk of peripheral neuropathy and is contraindicated (see Contraindications).

Other Interferons

The combination of Sebivo with other interferon formulations has not been adequately studied and is not recommended.

Drugs Affecting Renal Function

Since Sebivo is eliminated primarily by renal excretion, co-administration with medicines that affect renal function may alter Sebivo plasma concentrations; renal function should be monitored when such combinations are necessary.

Other Nucleoside Analogues

Sebivo is not recommended for use in combination with other nucleoside/nucleotide analogues used for hepatitis B (e.g., lamivudine), as combination has not shown added benefit and may increase the risk of adverse effects.

Common

• Fatigue
• Headache
• Cough
• Diarrhea
• Nausea
• Abdominal pain
• Elevated creatine kinase (CK)
• Upper respiratory tract infection

Serious (less common but important)

• Myopathy/rhabdomyolysis
• Peripheral neuropathy
• Lactic acidosis with severe hepatomegaly and steatosis
• Severe acute exacerbation of hepatitis B after stopping treatment

Patients should seek prompt medical attention for unexplained muscle pain, weakness, tenderness, numbness or tingling in the limbs, unusual fatigue, or difficulty breathing while taking Sebivo (see Precautions and Warnings).

Sebivo has been assigned to Pregnancy Category B in some regulatory classifications, based on animal reproduction studies that did not show evidence of harm to the fetus; however, adequate and well-controlled studies in pregnant women are limited. Sebivo should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus, and management should be individualized by a specialist, particularly when used as part of strategies to prevent perinatal (mother-to-child) transmission of hepatitis B. It is not known whether Sebivo is excreted in human breast milk; because many drugs are excreted in breast milk and due to the potential for adverse effects in the nursing infant, a decision should be made to discontinue breastfeeding or discontinue Sebivo, taking into account the importance of treatment to the mother. Always consult a physician before using Sebivo during pregnancy or while breastfeeding.

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with the use of nucleoside analogues including Sebivo. Treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of this condition.

Myopathy and Rhabdomyolysis

Sebivo has been associated with elevations in creatine kinase and, rarely, myopathy or rhabdomyolysis. Patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness; Sebivo should be discontinued if myopathy is confirmed or suspected.

Peripheral Neuropathy

Peripheral neuropathy has been reported, with increased risk when Sebivo is combined with pegylated interferon alfa-2a; this combination should be avoided (see Contraindications and Interactions).

Exacerbation of Hepatitis B After Discontinuation

Severe acute exacerbations of hepatitis B have been reported in patients who discontinued Sebivo. Liver function should be monitored closely, both clinically and with laboratory testing, for at least several months after stopping Sebivo; resumption of treatment may be warranted in some cases.

Development of Resistance

Prolonged use of Sebivo as monotherapy carries a risk of selecting for resistant HBV strains, which may reduce treatment effectiveness over time; adherence to the prescribed regimen and regular monitoring of viral load are important.

Renal Function

Because Sebivo is renally eliminated, dose adjustment is required in patients with impaired renal function (see Dosage and Administration); renal function should be assessed before and periodically during treatment.

Sebivo should always be taken exactly as prescribed; patients should not stop, skip, or alter their dose of Sebivo without consulting their physician, as this may lead to worsening of hepatitis B.

Limited clinical experience is available with Sebivo overdose. In the event of a suspected overdose of Sebivo, patients should seek immediate medical attention or contact a poison control center/emergency services. Management should include general supportive measures and monitoring of vital signs and clinical status; Sebivo is removed by hemodialysis, which may be considered if clinically indicated.

Store Sebivo at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Use

The safety and efficacy of Sebivo in patients younger than 18 years have not been established; use in this age group is not recommended.

Elderly (Geriatric) Use

Clinical studies of Sebivo have not included sufficient numbers of patients aged 65 and over. Since elderly patients are more likely to have decreased renal function, dose selection should be cautious and renal function should be monitored, with dose adjustment as needed (see Dosage and Administration).

Renal Impairment

Dose adjustment of Sebivo is required in patients with creatinine clearance below 50 mL/min, including those on hemodialysis (see Dosage and Administration).

Hepatic Impairment

No dose adjustment of Sebivo is required based on hepatic function.

HBV/HIV Co-infection

Sebivo has not been adequately studied in patients co-infected with HIV; such patients should be managed under specialist supervision.

The optimal duration of treatment with Sebivo for chronic hepatitis B has not been definitively established and should be individualized by the treating physician based on viral response (HBV DNA levels), hepatitis B e-antigen (HBeAg) status, and liver function tests. Treatment with Sebivo is generally long-term; patients should not discontinue therapy without medical supervision because of the risk of severe post-treatment exacerbation of hepatitis B.

Antiviral - Nucleoside (thymidine) analogue reverse transcriptase inhibitor, specific for hepatitis B virus.

Telbivudine is phosphorylated intracellularly to its active triphosphate form, which inhibits HBV DNA polymerase by competing with the natural nucleotide substrate and causing termination of the growing viral DNA chain, thereby suppressing HBV replication.

B

The safety and efficacy of Sebivo have not been established in pediatric patients (under 18 years of age). Sebivo is therefore not recommended for use in children and adolescents outside of a specialist clinical setting or clinical trial.