Lopinavir

Scientific discussion on Kaletra

Scientific discussion on Kaletra (lopinavir, ritonavir), Procedure No. EMEA/H/C/368/X/27 from 2006.

"For lopinavir, the PEC surface water was refined to 1.88 μg/L. The PEC surface water is greater than the limit of 0.01 μg/l proposed in the 2005 EMEA draft guidance. Concerning the estimation of the refined PEC/PNEC ratio, no data were available for the evaluation of lopinavir. An environmental risk assessment has not been adequately addressed by the MAH (Marketing Authorisation Holder ed. note) . Consequently, the MAH had to provide an environmental risk assessment for lopinavir according to the Note for Guidance on Environmental Risk Assessments for Pharmaceuticals (Draft CPMP/SWP/4447/00). [...] In response to the CHMP’s request, PEC_{surface water} of lopinavir had been re-calculated using modelling software and modelled physico-chemical values. Consequentially, PEC_{surface water} established using these modelled ecotoxicology data are not very reliable. Only the PEC_{surface water} values determined on measured ecotoxicology data can be take into consideration (PEC_{surface water} = 1,88 μg/l). However, this value exceeds the limit of 0.01 μg/l. No experimental studies have been performed. Instead the MAH provided ecotoxicology data modelled with a software (ECOSAR V 0.99e ). The lowest value of modelled ecotoxicology data of lopinavir could be considered with regard to NOEC of ritonavir. The lowest modelled NOEC is 1.914 mg/litre in green algae. If a conservative factor of 1000 is used, the estimated PNEC_WATER value is 1.914 μg/l. The PEC_{surface water}/PNEC_WATER ratio is below 1 and it could be considered that lopinavir is unlikely to represent a risk to the environment."

Assessment report for Kaletra

Assessment report for Kaletra 22 June 2017 EMA/CHMP/443456/2017.

"No updated environmental risk assessment for lopinavir and ritonavir has been provided. However, as stated in the EPAR of KALETRA that the lack of environmental risk assessment was considered acceptable since lopinavir degrades under UV-light and rapid breakdown is to be expected based on the molecular structure of lopinavir/ritonavir. Moreover, the MAH provided data on the low incidence of HIV in children under 2 years of age in EU (< 300/year). This extension of indication constitutes a marginal increased in the environmental exposure and the PEC_surfacewater value is below 0.01 µg/L based on the maximum daily dose."

Fass environmental information

Fass environmental information for Kaletra from AbbVie (downloaded 2020-04-07).

Hazard

Persistence: No data.

Bioaccumulation: "Log D_ow = 4.7. As the log D_ow is ≥ 4.0, lopinavir has high potential for bioaccumulation."

Toxicity: No data.

Risk

The environmental risk could not be calculated since there is not sufficient ecotoxicity data.