When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
4.6 Pregnancy and lactation Corrected the typographical error to replace the name ‘Zeffix’ with ‘Epivir’
4.8 Undesirable effects
· Updated the format of the frequency categorisation
· Added angiodema as a rare side effect
Warning/ Change in drug interactions (Epivir should not be taken with any other medicinal products containing lamivudine or medicinal products containing emtricitabine) & Update on pregnancy warnings
Addition of the following text:
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To ensure administration of the entire dose, the tablet(s) should ideally be swallowed without crushing. For patients who are unable to swallow tablets, lamivudine is available as an oral solution. Alternatively, the tablets may be crushed and added to a small amount of semi-solid food or liquid, all of which should be consumed immediately (see section 5.2).
5.2 Pharmacokinetic properties
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Administration of crushed tablets with a small amount of semi-solid food or liquid would not be expected to have an impact on the pharmaceutical quality, and would therefore not be expected to alter the clinical effect. This conclusion is based on the pharmacokinetic properties and physicochemical behaviour in water, and assumes that the patient crushes and transfers 100% of the tablet and ingests immediately.
Duration of treatment:
In patients with HBeAg positive chronic hepatitis B (CHB) treatment should be administered for at least 3-6 months afterHBeAg seroconversion (HBeAg and HBV DNA loss with HBeAb detection) is confirmed, to limit the risk of virological relapse, or until HBsAg seroconversion. This recommendation is based on limited data (see section 5.1).
Addition of the following wording to section 5.1:
Following HBeAg seroconversion, serologic response and clinical remission are generally durable after stopping lamivudine. However, relapse following seroconversion can occur. In a long-term follow-up study of patients who had previously seroconverted and discontinued lamivudine, late virological relapse occurred in 39% of the subjects. Therefore, following HBeAg seroconversion, patients should be periodically monitored to determine that serologic and clinical responses are being maintained. In patients who do not maintain a sustained serological response, consideration should be given to retreatment with either lamivudine or an alternative antiviral agent for resumption of clinical control of HBV.
Section 4.4 Addition of following:
Osteonecrosis: Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy (CART). Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Section 4.8, addition of following:
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term combined antiretroviral exposure (cART). The frequency of which is unknown (see section 4.4).