Lamivudine

Detailed information

Fass environmental information

Fass environmental information for Epivir (lamivudine) from GlaxoSmithKline (retrieved on 2025-10-01).

Hazard

Persistence: Degradation of lamivudine shows that the substance is neither readily biodegradable (< 1% in 28 days, OECD 301B) nor inherently biodegradable (0% in 28 days, OECD 302B). Primary degradation is low (4%), and soil degradation ranges between 15–24%. Simulation studies in aquatic sediment systems (OECD 308) indicate a total system half-life (DT₅₀) of 22–29 days, with 8.5–12.6% CO₂ formation and 8–9% non-extractable residues. Abiotic degradation via hydrolysis is very slow (half-life >1 year at pH 7, OECD 111), and no photolysis data are available. Based on these results, lamivudine is considered potentially persistent.

Bioaccumulation: Log D_ow at pH 5 = -1.17
Log D_ow at pH 7 = -1.44
Log D_ow at pH 9 = -1.86

Toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 10000 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2023.

PEC = 0.046 microg/L.

PNEC = Lowest NOEC, 10000 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 1000 microg/L.

PEC/PNEC = 0.000046 which gives the risk insignificant.

General information about assessment reports

Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data are available in the public assessment report (PAR/EPAR for centrally approved medicines). Environmental considerations are not included in the benefit-risk assessment for human medicines. If new data emerge after approval that necessitate an update of the environmental risk assessment, a variation application (“type IB C.I.z variation”) must be submitted to the regulatory authority.

The PEC (predicted environmental concentration) values used to calculate risk in the manufacturers' assessment reports are based on the estimated use of the medicinal product to which the assessment report relates, as well as possibly other products from the same company, not all medicinal products containing the same active substance.

Assessment reports

There are several assessment reports for different medicinal products containing lamivudine, most of which originate from GlaxoSmithKline/ViiV Healthcare B.V. Below is a recently published assessment report including environmental information, along with an additional assessment report for a generic product.

Assessment report Triumeq

Assessment report for lamivudine from Triumeq (abacavir, dolutegravir, lamivudine), ViiV Healthcare B.V., 15 December 2022, EMA/CHMP/915669/2022.

Hazard

Persistence: Lamivudine shows low soil adsorption (Koc 30–108) and is neither readily nor inherently biodegradable (DOC ≤ 1%). Primary degradation is 4%. In water-sediment systems (OECD 308), DT₅₀ is 22–29 days, indicating the substance is not persistent in sediment.

Bioaccumulation: Log D_ow at pH 5 = -1.86
Log D_ow at pH 7 = -1.44
Log D_ow at pH 9 = -1.17.
Please note that the Log D_ow values at pH 5 and pH 9 differ from those reported on fass.se. This discrepancy may be due to a transcription error or a reversal of values in one of the source documents.

Toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 10000 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC = 1.5 microg/L.

PNEC = Lowest NOEC, 10000 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = microg/L

PEC/PNEC = 0.0015 which gives the risk insignificant.

Assessment report Lamivudine Teva

Assessment report for Lamivudine Teva, Doc.Ref.: EMEA/640728/2009.

The applicant justified the absence of a formal environmental risk assessment, as the introduction of generics is not expected to increase overall sales of lamivudine-containing products or environmental exposure.

Comments on generics

After the implementation of the latest European Medicines Agency (EMA) ERA guideline (1 September 2024), a generic company has the following options for Article 10 procedures under Directive 2001/83/EC:

i) to argue that a full ERA is not required because the pharmaceutical substance belongs to certain substance groups (e.g., so-called natural substances);

ii) to identify an official ERA from a previously accepted product and use it; or

iii) to develop its own ERA according to the latest EMA ERA guideline.

Arguments for not submitting an Environmental Risk Assessment (ERA) based on the claim that total environmental exposure has not increased (via total sales volumes) belong to the previous ERA guideline system (2006–2024) and are no longer applicable. Regarding option ii), it should be noted that if a reference ERA exists, the generic company must demonstrate that its conclusions remain technically relevant (since the latest ERA guideline introduced several new technical requirements absent in the previous ERA guideline) and in terms of exposure (showing that the estimated exposure used in the reference ERA remains reasonable). Regulatory authorities (national and EMA) recommend that generic companies attempt to obtain reference ERA documentation from other companies via a so-called Letter of Access (LoA). However, if this is not possible, it remains feasible to argue that the conclusions of an existing reference ERA are still relevant based on information gathered from public assessment reports (summarized descriptions of environmental risk assessments) and product information (to confirm that dosages, indications, etc., have not changed). It should be noted that in some cases, reference ERAs approved between 2006 and 2024 may need to be modified (e.g., with additional experimental studies). If no previous reference ERA can be identified or used, the generic company must commit to developing its own ERA.