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Zeffix is a brand name for Lamivudine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Zeffix is indicated for the treatment of chronic hepatitis B in adults with: ▪ compensated liver disease with evidence of active viral replication, persistently elevated serum alanine aminotransferase (ALT) levels and histological evidence of active liver inflammation and/or fibrosis. Initiation of lamivudine…
Verbatim from this product's EMA label. Tap a section to expand.
Therapy with Zeffix should be initiated by a physician experienced in the management of chronic hepatitis B. Posology Adults The recommended dosage of Zeffix is 100 mg once daily. In patients with decompensated liver disease, lamivudine should always be used in combination with a second agent, without cross-resistance to lamivudine, to reduce the risk of resistance and to achieve rapid viral suppression.
Duration of treatment The optimal duration of treatment is unknown. 4). Serum ALT and HBV DNA levels 3 should be followed regularly after treatment discontinuation to detect any late virological relapse. • In patients with HBeAg negative CHB (pre-core mutant) without cirrhosis, treatment should be administered at least until HBs seroconversion or there is evidence of loss of efficacy.
With prolonged treatment, regular reassessment is recommended to confirm that continuation of the selected therapy remains appropriate for the patient. 1). 4). Clinical resistance In patients with either HBeAg positive or HBeAg negative CHB, the development of YMDD (tyrosine-methionine-aspartate-aspartate) mutant HBV may result in a diminished therapeutic response to lamivudine, indicated by a rise in HBV DNA and ALT from previous on-treatment levels.
1). Special populations Renal impairment Lamivudine serum concentrations (AUC) are increased in patients with moderate to severe renal impairment due to decreased renal clearance. The dosage should, therefore, be reduced for patients with a creatinine clearance of < 50 ml/minute.
When doses below 100 mg are required Zeffix oral solution should be used (see Table 1 below).
Table 1:
Dosage of Zeffix in patients with decreased renal clearance. Creatinine clearance ml/min First dose of Zeffix oral solution * Maintenance dose once daily 30 to < 50 20 ml (100 mg) 10 ml (50 mg) 15 to < 30 20 ml (100 mg) 5 ml (25 mg) 5 to < 15 7 ml (35 mg) 3 ml (15 mg) < 5 7 ml (35 mg) 2 ml (10 mg) * Zeffix oral solution containing 5 mg/ml lamivudine.
Data available in patients undergoing intermittent haemodialysis (for less than or equal to 4 hrs dialysis 2-3 times weekly), indicate that following the initial dosage reduction of lamivudine to correct for the patient’s creatinine clearance, no further dosage adjustments are required while undergoing dialysis.
Summary of the safety profile The incidence of adverse reactions and laboratory abnormalities (with the exception of elevations of ALT and CPK, see below) were similar between placebo and lamivudine treated patients. The most common adverse reactions reported were malaise and fatigue, respiratory tract infections, throat and tonsil discomfort, headache, abdominal discomfort and pain, nausea, vomiting and diarrhoea.
Tabulated list of adverse reactions Adverse reactions are listed below by system organ class and frequency. Frequency categories are only assigned to those adverse reactions considered to be at least possibly causally related to lamivudine.
Frequencies are defined as: very common ( 1/10), common ( 1/100 to < 1/10), uncommon ( 1/1000 to < 1/100), rare ( 1/10,000 to < 1/1000), very rare (< 1/10,000) and not known (cannot be estimated from the available data). The frequency categories assigned to the adverse reactions are mainly based on experience from clinical trials including a total of 1,171 patients with chronic hepatitis B receiving lamivudine at 100 mg.
4) Exacerbations of hepatitis, primarily detected by serum ALT elevations, have been reported ‘on-treatment’ and following lamivudine withdrawal. 4). Skin and subcutaneous tissue disorders Common Rash, pruritus Musculoskeletal and connective tissue disorders Common Elevations of CPK Common Muscle disorders, including myalgia and cramps* Not known Rhabdomyolysis * In Phase III studies frequency observed in the lamivudine treatment group was not greater than observed in the placebo group 9 Paediatric population Based on limited data in children aged 2 to 17 years, there were no new safety issues identified compared to adults.
Other special populations In patients with HIV infection, cases of pancreatitis and peripheral neuropathy (or paresthesia) have been reported. In patients with chronic hepatitis B there was no observed difference in incidence of these events between placebo and lamivudine treated patients.
Exacerbations of hepatitis Exacerbations on treatment Spontaneous exacerbations in chronic hepatitis B are relatively common and are characterised by transient increases in serum ALT. After initiating antiviral therapy, serum ALT may increase in some patients as serum HBV DNA levels decline.
In patients with compensated liver disease, these increases in serum ALT were generally not accompanied by an increase in serum bilirubin concentrations or signs of hepatic decompensation. HBV viral subpopulations with reduced susceptibility to lamivudine (YMDD mutant HBV) have been identified with extended therapy.
2). 1). Exacerbations after treatment discontinuation Acute exacerbation of hepatitis has been observed in patients who have discontinued hepatitis B therapy and is usually detected by serum ALT elevations and re-emergence of HBV DNA.
In the controlled Phase III trials with no-active-treatment follow-up, the incidence of post-treatment ALT elevations (more than 3 times baseline) was higher in lamivudine-treated patients (21%) compared with those receiving placebo (8%).
1). For lamivudine-treated patients, the majority of post-treatment ALT elevations occurred between 8 and 12 weeks post-treatment. Most events have been self-limiting, however some fatalities have been observed. If Zeffix is discontinued, patients should be periodically monitored both clinically and by assessment of serum liver function tests (ALT and bilirubin levels), for at least four months, and then as clinically indicated.
Exacerbations in patients with decompensated cirrhosis Transplantation recipients and patients with decompensated cirrhosis are at greater risk from active viral replication. Due to the marginal liver function in these patients, hepatitis reactivation at 5 discontinuation of lamivudine or loss of efficacy during treatment may induce severe and even fatal decompensation.
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Hepatic impairment Data obtained in patients with hepatic impairment, including those with end-stage liver disease awaiting transplant, show that lamivudine pharmacokinetics are not significantly affected by hepatic dysfunction. Based on these data, no dose adjustment is necessary in patients with hepatic impairment unless accompanied by renal impairment.
4 HIV co-infection For the treatment of patients who are co-infected with HIV and are currently receiving or plan to receive combined antiretroviral treatment including lamivudine, the dose of lamivudine prescribed for HIV infection (usually 150 mg/twice daily in combination with other antiretrovirals) should be used.
Elderly In elderly patients, normal ageing with accompanying renal decline has no clinically significant effect on lamivudine exposure, except in patients with creatinine clearance of < 50 ml/min. Paediatric population The safety and efficacy of Zeffix in infants, children and adolescents aged below 18 years have not been established.
1 but no recommendation on a posology can be made. Method of administration Oral use. Zeffix can be taken with or without food.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
These patients should be monitored for clinical, virological and serological parameters associated with hepatitis B, liver and renal function, and antiviral response during treatment (at least every month), and, if treatment is discontinued for any reason, for at least 6 months after treatment.
Laboratory parameters to be monitored should include (as a minimum) serum ALT, bilirubin, albumin, blood urea nitrogen, creatinine, and virological status: HBV antigen/antibody, and serum HBV DNA concentrations when possible. Patients experiencing signs of hepatic insufficiency during or post-treatment should be monitored more frequently as appropriate.
For patients who develop evidence of recurrent hepatitis post-treatment, there are insufficient data on the benefits of re-initiation of lamivudine treatment. Mitochondrial dysfunction Nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage.
There have been reports of mitochondrial dysfunction in infants exposed in utero and/or post-natally to nucleoside analogues. The main adverse events reported are haematological disorders (anaemia, neutropenia), metabolic disorders (hyperlipasemia).
Some late-onset neurological disorders have been reported (hypertonia, convulsion, abnormal behaviour). The neurological disorders might be transient or permanent. Any child exposed in utero to nucleoside and nucleotide analogues, should have clinical and laboratory follow-up and should be fully investigated for possible mitochondrial dysfunction in cases which have relevant signs or symptoms.
Paediatric patients Lamivudine has been administered to children (2 years and above) and adolescents with compensated chronic hepatitis B. 1). Delta hepatitis or hepatitis C The efficacy of lamivudine in patients co-infected with Delta hepatitis or hepatitis C has not been established and caution is advised.
Immunosuppressive treatments Data are limited on the use of lamivudine in HBeAg negative (pre-core mutant) patients and in those receiving concurrent immunosuppressive regimes, including cancer chemotherapy. Lamivudine should be used with caution in these patients.
Monitoring During treatment with Zeffix patients should be monitored regularly. Serum ALT and HBV DNA levels should be monitored at 3 month intervals and in HBeAg positive patients HBeAg should be assessed every 6 months. HIV co-infection For the treatment of patients who are co-infected with HIV and are currently receiving or plan to receive treatment with an antiretroviral combination regimen including lamivudine, the dose of lamivudine prescribed for HIV infection (usually 150 mg/twice daily in combination with other antiretrovirals) should be used.
The 100 mg usual dose of lamivudine used for the treatment of HBV is not appropriate for patients who acquire HIV or are co-infected with HBV and HIV. If a patient with unrecognised or untreated HIV infection is prescribed the dose of lamivudine recommended for the treatment of HBV, rapid emergence of HIV resistance and a limitation of treatment options is likely to result because of the 6 subtherapeutic dose and the inappropriate use of monotherapy for HIV treatment.
HIV counselling and testing should be offered to all patients before beginning treatment with lamivudine for HBV and periodically during treatment. Transmission of hepatitis B There is no […]