Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland
Zeffix is indicated for the treatment of chronic hepatitis B in adults with:
Therapy with Zeffix should be initiated by a physician experienced in the management of chronic hepatitis B.
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.
The optimal duration of treatment is unknown.
If lamivudine is discontinued, patients should be periodically monitored for evidence of recurrent hepatitis (see section 4.4).
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. In order to reduce the risk of resistance in patients receiving lamivudine monotherapy, a switch to or addition of an alternative agent without cross-resistance to lamivudine based on therapeutic guidelines should be considered if serum HBV DNA remains detectable at or beyond 24 weeks of treatment (see section 5.1).
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 έως < 50 | 20 ml (100 mg) | 10 ml (50 mg) |
| 15 έως < 30 | 20 ml (100 mg) | 5 ml (25 mg) |
| 5 έως < 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.
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.
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.
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.
The safety and efficacy of Zeffix in infants, children and adolescents aged below 18 years have not been established. Currently available data are described in sections 4.4 and 5.1 but no recommendation on a posology can be made.
Oral use.
Zeffix can be taken with or without food.
No specific signs or symptoms have been identified following acute overdose with lamivudine, apart from those listed as adverse reactions.
If overdose occurs the patient should be monitored and standard supportive treatment applied as required. Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of overdose, although this has not been studied.
3 years.
Do not store above 30ºC.
Double foil blisters, laminated with polyvinyl chloride.
Pack sizes of 28 or 84 film-coated tablets.
Not all pack-sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
