Dolutegravir

Detailed information

Assessment reports

There are several assessment reports on dolutegravir from Dovato, Triumeq, Juluca, and Tivicay submitted by ViiV Healthcare UK Limited/ViiV Healthcare B.V. The most recent assessment report containing more comprehensive environmental information is from 26 April 2019, concerning Dovato (dolutegravir, lamivudine), reference EMA/267082/2019.

Hazard

Persistence: "The DTG (dolutegravir) shows a DT₅₀ > 1y in water sediment systems and in soil and can be considered very persistent (vP) in the environment."

Bioaccumulation: log D_ow -2.45.

Toxicity: There are data for 3 trophic levels, most sensitive algae NOEC 95.4 microg/L.

Risk

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

PEC refined = between 0.0047 and 0.0126µg/L.

PNEC = Lowest NOEC, 95.4 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 9.54 microg/L

PEC/PNEC = 0.0013 which gives the risk insignificant.

Variation assessment report

The most recent assessment report for the extension of indication is for Triumeq (dolutegravir, abacavir, and lamivudine), dated 25 April 2024, reference EMA/CHMP/136294/2024.

The MAH (Marketing Authorisation Holder) submitted an updated environmental risk assessment (ERA) for Triumeq, reaffirming that the previously approved 2017 ERA remains valid. The proposed dispersible tablet formulation for children under 25 kg contains only 10% of the adult dose. All scenarios, including the most conservative worst-case phase I PEC, indicated that the use of Triumeq is unlikely to be a risk to the environment (PEC/PNEC < 1). The slight increase in patient numbers is not expected to significantly raise environmental exposure.

Remarks regarding the PEC

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.

Fass environmental information

Fass environmental information for dolutegravir from Dovato (dolutegravir, lamivudine) from GlaxoSmithKline (retrieved on 2025-06-25).

Hazard

Persistence: "Dolutegravir is not readily biodegradable nor inherently biodegradable. This substance is predicted to degrade in water sediment systems ≥ 120 days. Non-extractable residues represent < 10% of the total material. The phrase “Dolutegravir is potentially persistent” is thus chosen."

Bioaccumulation: Log D_ow < 1 at pH 7 (OECD 107)
Log D_ow at pH 5 = -2.28
Log D_ow at pH 7 = -2.45
Log D_ow at pH 9 = -3.21

Toxicity: There are data for 3 trophic levels, most sensitive algae NOEC 95 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2022. PEC/PNEC = 0.00114 which gives the risk insignificant.