Zeffix Special Precautions

Initiation of lamivudine treatment should only be considered when the use of an alternative antiviral agent with a higher genetic barrier to resistance is not available or appropriate. During initiation and maintenance of treatment patients should be monitored regularly by a physician experienced in the management of chronic hepatitis B.
If ZEFFIX is discontinued or there is a loss of efficacy, some patients may experience clinical or laboratory evidence of recurrent hepatitis. Exacerbation of hepatitis has primarily been detected by serum ALT elevations, in addition to the re-emergence of HBV DNA. See Table 1 in Clinical Studies for more information regarding frequency of post-treatment ALT elevations. Most events appear to have been self-limited. Fatalities are very rare and the causal relationship to discontinuation of ZEFFIX treatment is unknown.
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 for evidence of recurrent hepatitis; patients should then be followed as clinically indicated. For patients who develop evidence of recurrent hepatitis post-treatment, there are insufficient data on the benefits of re-initiation of ZEFFIX treatment.
In patients with moderate to severe renal impairment, serum lamivudine concentrations (AUC) are increased due to decreased renal clearance, therefore the dose should be reduced for patients with a creatinine clearance of less than 50 ml/minute (see Dosage & Administration).
Transplantation recipients and patients with advanced liver disease are at greater risk from active viral replication. Due to marginal liver function in these patients, hepatitis reactivation at discontinuation of ZEFFIX or loss of efficacy during treatment may induce severe and even fatal decompensation. It is recommended that these patients are monitored for parameters associated with hepatitis B, for liver and renal function, and for antiviral response during treatment. If treatment is discontinued for any reason, it is recommended that these patients are monitored for at least 6 months post cessation of treatment. Patients experiencing signs of hepatic insufficiency during or post-treatment should be monitored frequently, as appropriate.
There are limited data on the use of ZEFFIX in patients receiving concurrent immunosuppressive regimes, including cancer chemotherapy.
In HBeAg positive or negative patients, 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 should be considered if serum HBV DNA remains detectable at or beyond 24 weeks of treatment (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
For the treatment of patients who are coinfected with HIV and are currently receiving or are planning to receive an antiretroviral treatment regimen including lamivudine, the dose of lamivudine usually prescribed for HIV infection should be maintained.
There is limited information available on maternal-foetal transmission of hepatitis B virus in pregnant women receiving treatment with ZEFFIX. The standard recommended procedures for hepatitis B virus immunisation in infants should be followed.
Patients should be advised that therapy with ZEFFIX has not been proven to reduce the risk of transmission of hepatitis B virus to others and therefore, appropriate precautions should still be taken.
Effects on Ability to Drive and Use Machines: There have been no studies to investigate the effect of ZEFFIX on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities would not be predicted from the pharmacology of the drug.