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  • Sebivo
    / Novartis


    Active Ingredient
    Telbivudine 600 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    28 X 600 mg

    partial basket chart 86389 19849

    Dosage

    Adults: The recommended dose of Sebivo for the treatment of chronic hepatitis B is 600 mg once daily, taken orally, with or without food. Due to risk of higher rates of resistance that may develop with longer term treatment among patients with incomplete viral suppression, treatment should only be initiated after baseline HBV DNA criteria are met.
    Monitoring and duration of treatment: On-treatment response at week 24 has been shown to be predictive of longer-term response. HBV DNA levels should be monitored at 24 weeks of treatment to assure complete viral suppression (HBV DNA less than 300 copies/mL). Alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment. HBV DNA should be monitored every 6 months to assure continued response. If patients are tested positive for HBV DNA at any time after their initial response, alternate treatment should be instituted. Optimal treatment should be guided by resistance testing. The optimal treatment duration has not been established.
    Renal impairment/insufficiency: Sebivo may be used for the treatment of chronic hepatitis B in patients with impaired renal function. No adjustment of the recommended dose of telbivudine is necessary in patients whose creatinine clearance is ≥50 mL/min. Dose adjustment is required in patients with creatinine clearance <50 mL/min including those with end stage renal disease (ESRD) on haemodialysis.
    End Stage Renal Disease (ESRD) patients: For patients with ESRD, Sebivo should be administered after haemodialysis.
    Hepatic impairment: No adjustment of the recommended dose of Sebivo is necessary in patients with hepatic impairment.
    Paediatric patients (age below 16 years): No studies have been performed in children under the age of 16 years. Therefore, until more information is available, Sebivo is not recommended for use in children.
    Elderly patients (age above 65 years): No data are available to support a specific dose recommendation for patients over the age of 65 years.
    Missed Doses: If a dose is missed, the patient may take the missed dose only up to 4 hours prior to the next scheduled dose. The next dose should be taken at the usual time.
    For full details see prescribing information.


    Indications

    Sebivo is indicated for the treatment of chronic hepatitis B in patients with evidence of viral replication and active liver inflammation in adults over 16 years of age.  The following points should be considered when initiating therapy with Sebivo: For HBeAg-positive patients, Sebivo treatment should only be initiated in patients with baseline HBV DNA < 9log 10 copies/mL and baseline ALT ≥ 2x ULN. For HBeAg-negative patients, Sebivo treatment should only be initiated in patients with baseline HBV DNA < 7 log 10 copies/mL.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients. Combination of telbivudine with pegylated or standard interferon alfa.


    Special Precautions

    Severe acute exacerbations of chronic hepatitis B are relatively frequent, and are characterised by transient elevation of serum ALT. Following initiation of antiviral treatment, serum ALT may rise in some patients while serum levels of HBV DNA fall. On average, 4-5 weeks elapsed prior to the occurrence of an exacerbation in patients treated with telbivudine. Overall, ALT flares occurred more frequently in HBeAg-positive patients than in HBeAg-negative patients. In patients with compensated liver disease, this elevation of serum ALT is generally not accompanied by elevated levels of serum bilirubin or by other signs of hepatic decompensation. The risk of hepatic decompensation – and of a subsequent exacerbation of hepatitis – may be elevated in patients with cirrhosis. Such patients should therefore be closely monitored.
    Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy. Hepatic function must be monitored closely, with both clinical and laboratory follow-up for at least 6 months in patients who discontinue antihepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
    Lactic acidosis: Rare post-marketing cases of lactic acidosis have been reported with telbivudine. Cases were more often secondary to other serious conditions (e.g. rhabdomyolysis) and/or associated muscle-related events (e.g. myopathy, myositis). When secondary to other conditions, some cases were also associated with pancreatitis, liver failure/hepatic steatosis and renal failure. In some cases, fatal outcomes were reported when lactic acidosis was secondary to rhabdomyolysis. Patients should be followed closely. Treatment with telbivudine should be discontinued when metabolic/lactic acidosis of unknown aetiology occurs. Benign digestive symptoms, such as nausea, vomiting and abdominal pain, may be indicative of lactic acidosis development.
    Muscular effects: Cases of myopathy and myalgia have been reported with telbivudine use several weeks to months after starting therapy. Myopathy has also been reported with some other drugs in this class. Isolated cases of rhabdomyolysis have been reported during post-marketing use of telbivudine Uncomplicated myalgia has been reported in telbivudine-treated patients. Myopathy, defined as persistent unexplained muscle aches and/or muscle weakness regardless of the degree of increases in creatine kinase (CK) levels, should be considered in any patient with unexplained diffuse myalgias, muscle tenderness or muscle weakness. Among patients with telbivudine-associated myopathy, there has not been a uniform pattern with regard to the degree or timing of CK elevations. In addition, the predisposing factors for the development of myopathy among telbivudine recipients are unknown. Patients should be advised to report promptly any persistent unexplained muscle aches, pain, tenderness or weakness. Telbivudine therapy should be discontinued if myopathy is diagnosed. It is not known if the risk of myopathy during treatment with drugs in this class is increased with concurrent administration of other drugs associated with myopathy (e.g. statins, fibrates, or ciclosporin). Physicians considering concomitant treatment with other agents associated with myopathy should weigh carefully the potential benefits and risks and should monitor patients for any signs or symptoms of unexplained muscle pain, tenderness, or weakness.
    Peripheral neuropathy: Peripheral neuropathy has been uncommonly reported in telbivudine-treated patients. If peripheral neuropathy is suspected, treatment with telbivudine should be reconsidered.
    Renal function: Telbivudine is eliminated primarily by renal excretion, therefore dose interval adjustment is recommended in patients with creatinine clearance <50 mL/min, including patients on haemodialysis. The effectiveness of dosing interval adjustment has not been clinically evaluated. Therefore, virological response should be closely monitored in patients with increased dosage interval.
    Patients with cirrhosis without decompensation: Due to the limited data available (about 3% of patients enrolled had cirrhosis), telbivudine should be used with particular caution in cirrhotic patients. These patients should be closely monitored for clinical, biochemical and virological parameters associated with hepatitis B during treatment and after treatment is discontinued.
    Patients with cirrhosis with decompensation: There are no efficacy and safety data in patients with decompensated cirrhosis. Sebivo is not indicated in patients with decompensated cirrhosis.
    Patients with previous exposure to nucleoside/nucleotide analogues: In vitro, telbivudine was not active against the HBV strains containing rtM204V/rtL180M or rtM204I mutations (see section 5.1). Telbivudine monotherapy is not an option for patients with established lamivudine-resistant hepatitis B virus infection. Patients who failed to achieve virological response following treatment with lamivudine for more than 24 weeks are unlikely to benefit from telbivudine monotherapy. There is currently no clinical data to properly assess the benefit and risk of switching to telbivudine for lamivudine-treated patients who achieve complete viral suppression on lamivudine. There are no data on telbivudine treatment in patients with established adefovir-resistant hepatitis B virus single mutations of rtN236T or A181V. Results from cell-based assays showed that the adefovir resistance-associated substitution A181V had 1.5- to approximately 4-fold reduced susceptibility to telbivudine.
    Liver transplant recipients: The safety and efficacy of telbivudine in liver transplant recipients are unknown.
    Use in elderly patients: Clinical studies of telbivudine did not include sufficient numbers of patients ≥ 65 years of age to determine whether they respond differently from younger subjects. In general, caution must be exercised when prescribing Sebivo to elderly patients in view of the greater frequency of decreased renal function due to concomitant disease or concomitant use of other medicinal products.
    Other Special populations: Sebivo has not been investigated in co-infected hepatitis B patients (e.g. patients co-infected with HIV, HCV or HDV).
    For full details see prescribing information.


    Side Effects

    Common: Dizziness, headache, Cough, Diarrhoea, blood lipase increased, nausea, abdominal pain, Rash, Fatigue, Blood creatine phosphokinase increased, blood alanine aminotransferase increased, blood amylase increased.
    For full details see prescribing information.


    Drug interactions

    Since telbivudine is eliminated primarily by renal excretion, co-administration of Sebivo with substances that affect renal function (such as aminoglycosides, loop diuretics, platinum compounds, vancomycin, amphotericin B) may affect plasma concentrations of telbivudine and/or the co-administered substance. The combination of telbivudine with these medicinal products should be used with caution. The steady-state pharmacokinetics of telbivudine were unaltered following multiple dose administration in combination with lamivudine, adefovir dipivoxil, tenofovir disoproxil fumarate , ciclosporin or pegylated interferon-alfa 2a. In addition, telbivudine does not alter the pharmacokinetics of lamivudine, adefovir dipivoxil, tenofovir disoproxil fumarate or ciclosporin. No definitive conclusion could be drawn regarding the effects of telbivudine on the pharmacokinetics of pegylated interferon due to high interindividual variability of pegylated interferon-alfa 2a concentrations.
    A clinical trial investigating the combination of telbivudine, 600 mg daily, with pegylated interferon alfa-2a, 180 micrograms once weekly by subcutaneous administration, indicates that this combination is associated with an increased risk of developing peripheral neuropathy. The mechanism behind these events is not known. The combination of telbivudine with any interferon alfa-containing product is contraindicated Telbivudine is not a substrate, inhibitor or inducer of the cytochrome P450 (CYP450) enzyme system. Therefore, the potential for CYP450-mediated drug interactions involving Sebivo is low.
    For full details see prescribing information.


    Pregnancy and Lactation

    Pregnancy: Sebivo should be used during pregnancy only if the benefit to the mother outweighs the potential risk to the foetus.
    Lactation: Telbivudine is excreted in the milk of rats. It is not known whether telbivudine is excreted in human milk. Women should not breastfeed if they are taking Sebivo.


    Overdose

    No case of overdose with Sebivo has been reported. Tested doses up to 1,800 mg/day, three times greater than the recommended daily dose, have been well tolerated. A maximum tolerated dose of telbivudine has not been determined. In the event of an overdose, Sebivo should be discontinued and appropriate general supportive treatment applied as necessary.


    Important notes

    Storage: Store in the original package below 30°c.


    Manufacturer
    Novartis Pharma Stein AG Switzerland
    Licence holder
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