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.
4.8 Undesirable effects
· Updated the format of the frequency categorisation · Added angiodema as a rare side effect
· Added angiodema as a rare side effect
Changes:
Addition in red, deletion in blue
4.4 Special warnings and precautions for use
Epivir should not be taken with any other medicinal products containing lamivudine or medicinal products containing emtricitabine.
4.5 Interaction with other medicinal products and other forms of interaction
Interaction studies have only been performed in adults
Lamivudine may inhibit the intracellular phosphorylation of zalcitabine when the two medicinal products are used concurrently. Epivir is therefore not recommended to be used in combination with zalcitabine.
Co-administration of lamivudine with intravenous ganciclovir or foscarnet is not recommended.
(e.g. didanosine and zalcitabine) like
4.6 Pregnancy and lactation
A large amount of data on pregnant women (more than 1000 exposed outcomes) indicate no malformative toxicity. Epivir can be used during pregnancy if clinically needed.
For patients co-infected with hepatitis who are being treated with lamivudine and subsequently become pregnant, consideration should be given to the possibility of a recurrence of hepatitis on discontinuation of lamivudine.
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 (see section 4.4).
Pregnancy: The safety of lamivudine in human pregnancy has not been established. Reproductive studies in animals have not shown evidence of teratogenicity, and showed no effect on male or female fertility. Lamivudine induces early embryonic death when administered to pregnant rabbits at exposure levels comparable to those achieved in man. In humans, consistent with passive transmission of lamivudine across the placenta, lamivudine concentrations in infant serum at birth were similar to those in maternal and cord serum at delivery.
Although animal reproductive studies are not always predictive of the human response, administration is not recommended during the first three months of pregnancy.
Lactation:
5.1 regarding M184V resistance.
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).